SHM asked Academic Hospitalist Academy course co-directors Jeffrey Glasheen, MD, SFHM, and Bradley Sharpe, MD, SFHM, why academic hospitalists should attend this year’s academy.

Question: What has you personally excited about this year’s Academic Hospitalist Academy?

Dr. Sharpe: I’ll be honest—it is one of my favorite weeks of the year. It is a tremendous opportunity to engage with academic hospitalists and help them develop the core skills they need to be successful.

Dr. Glasheen: For me, it’s about the energy, the talent, and the excitement that the attendees bring to the course. It ends up being a tremendously energizing week for me personally. To see the talent in the room begin to find outlets for success is truly invigorating.

Q: If you were talking one on one with an academic hospitalist, what would you say to encourage them to attend?

Dr. Sharpe: Based on previous attendees, these four days could truly change your life. We are confident you will leave with newfound energy and enthusiasm and key building blocks to help you be successful when you go back home. Don’t miss it.

Dr. Glasheen: There is a magical transformation that happens every year. Very talented individuals enter the program. Nearly uniformly, they are struggling with the same issues around mentorship, sense of purpose, direction, and resources for success. They all want to be successful but sense there is something that is missing, and within the course of four days, they find it.

Q: What have you heard from previous AHA attendees?

Dr. Sharpe: Here are a couple of emails I received: “I can’t say enough about the AHA. It was possibly the most important 3 days of my young career. Thank you both for the knowledge and guidance.” “I have fond memories of the whole AHA conference. The great Jeff Wiese!!! But most of all, the small group sessions were extremely helpful.”

Dr. Glasheen: To a person, they all say the meeting is “transformational.” They gain skills in teaching, confidence in evaluating learners, methods for scholarly success, and a roadmap for navigating the tricky world on academic medicine. But beyond that, they gain a peer network. They leave tied in with 80 other national colleagues that are struggling with the same issues. This network becomes their home away from home—people they can turn to with a question, catch up with at a national meeting, and look to as exemplars in the field.

SHM asked Academic Hospitalist Academy course co-directors Jeffrey Glasheen, MD, SFHM, and Bradley Sharpe, MD, SFHM, why academic hospitalists should attend this year’s academy.

Question: What has you personally excited about this year’s Academic Hospitalist Academy?

Dr. Sharpe: I’ll be honest—it is one of my favorite weeks of the year. It is a tremendous opportunity to engage with academic hospitalists and help them develop the core skills they need to be successful.

Dr. Glasheen: For me, it’s about the energy, the talent, and the excitement that the attendees bring to the course. It ends up being a tremendously energizing week for me personally. To see the talent in the room begin to find outlets for success is truly invigorating.

Q: If you were talking one on one with an academic hospitalist, what would you say to encourage them to attend?

Dr. Sharpe: Based on previous attendees, these four days could truly change your life. We are confident you will leave with newfound energy and enthusiasm and key building blocks to help you be successful when you go back home. Don’t miss it.

Dr. Glasheen: There is a magical transformation that happens every year. Very talented individuals enter the program. Nearly uniformly, they are struggling with the same issues around mentorship, sense of purpose, direction, and resources for success. They all want to be successful but sense there is something that is missing, and within the course of four days, they find it.

Q: What have you heard from previous AHA attendees?

Dr. Sharpe: Here are a couple of emails I received: “I can’t say enough about the AHA. It was possibly the most important 3 days of my young career. Thank you both for the knowledge and guidance.” “I have fond memories of the whole AHA conference. The great Jeff Wiese!!! But most of all, the small group sessions were extremely helpful.”

Dr. Glasheen: To a person, they all say the meeting is “transformational.” They gain skills in teaching, confidence in evaluating learners, methods for scholarly success, and a roadmap for navigating the tricky world on academic medicine. But beyond that, they gain a peer network. They leave tied in with 80 other national colleagues that are struggling with the same issues. This network becomes their home away from home—people they can turn to with a question, catch up with at a national meeting, and look to as exemplars in the field.

SHM asked Academic Hospitalist Academy course co-directors Jeffrey Glasheen, MD, SFHM, and Bradley Sharpe, MD, SFHM, why academic hospitalists should attend this year’s academy.

Question: What has you personally excited about this year’s Academic Hospitalist Academy?

Dr. Sharpe: I’ll be honest—it is one of my favorite weeks of the year. It is a tremendous opportunity to engage with academic hospitalists and help them develop the core skills they need to be successful.

Dr. Glasheen: For me, it’s about the energy, the talent, and the excitement that the attendees bring to the course. It ends up being a tremendously energizing week for me personally. To see the talent in the room begin to find outlets for success is truly invigorating.

Q: If you were talking one on one with an academic hospitalist, what would you say to encourage them to attend?

Dr. Sharpe: Based on previous attendees, these four days could truly change your life. We are confident you will leave with newfound energy and enthusiasm and key building blocks to help you be successful when you go back home. Don’t miss it.

Dr. Glasheen: There is a magical transformation that happens every year. Very talented individuals enter the program. Nearly uniformly, they are struggling with the same issues around mentorship, sense of purpose, direction, and resources for success. They all want to be successful but sense there is something that is missing, and within the course of four days, they find it.

Q: What have you heard from previous AHA attendees?

Dr. Sharpe: Here are a couple of emails I received: “I can’t say enough about the AHA. It was possibly the most important 3 days of my young career. Thank you both for the knowledge and guidance.” “I have fond memories of the whole AHA conference. The great Jeff Wiese!!! But most of all, the small group sessions were extremely helpful.”

Dr. Glasheen: To a person, they all say the meeting is “transformational.” They gain skills in teaching, confidence in evaluating learners, methods for scholarly success, and a roadmap for navigating the tricky world on academic medicine. But beyond that, they gain a peer network. They leave tied in with 80 other national colleagues that are struggling with the same issues. This network becomes their home away from home—people they can turn to with a question, catch up with at a national meeting, and look to as exemplars in the field.

Hospitalist Robert McNab, DO, has been named the new medical education director of Freeman Health System in Joplin, Mo. He will continue as a hospitalist and director of the internal-medicine residency program. Dr. McNab brings more than 10 years of teaching experience to the Freeman Graduate Medical Education Program.

Brian Harte, MD, SFHM, Cleveland Clinic hospitalist and president of South Pointe Hospital in Warrensville Heights, Ohio, is now president of Hillcrest Hospital in Mayfield Heights, Ohio. Dr. Harte is an SHM board member and serves as the board treasurer. In addition to his new role, Dr. Harte will continue to practice as a hospitalist at Hillcrest Hospital.

Anita Dhople, MD, is the new hospitalist medical director for the Rockledge, Fla.-based Health First health system. Dr. Dhople will oversee all hospitalist services at four affiliated hospitals. Dr. Dhople comes to Health First from the Piedmont Physicians Group in Atlanta.

Matthew Heinz, MD, has been appointed director of provider outreach in the U.S. Department of Health and Human Services’ Office of Intergovernmental and External Affairs (IEA). Dr. Heinz is a practicing hospitalist at Tucson (Ariz.) Medical Center and a former representative in the Arizona state legislature.

Business Moves

IPC: The Hospitalist Company, based in North Hollywood, Calif., has announced the acquisition of two private hospitalist practices: Sound Senior Geriatrics LLC (SSG) in Mystic, Conn., and Cape Coral Hospitalists Inc. (CCH) based in Fort Meyers, Fla. IPC contracts hospitalist services in 28 states.

Bayhealth hospital network in Dover, Del., has partnered with Apogee Physicians to provide 24-hour hospitalist services at Kent General Hospital in Dover and Milford Memorial Hospital in Milford. Bayhealth has been serving communities in central and southern Delaware for more than 75 years. Phoenix-based Apogee Physicians has been providing contracted hospitalist services since 2002.

Cogent Healthcare is partnering with South Georgia Medical Center (SGMC) to provide hospitalist services at the 285-bed acute-care nonprofit main campus and the 55-bed Smith Northview Campus in Valdosta, Ga. SGMC currently serves 15 counties in south-central Georgia and north Florida. Cogent provides contracted hospitalist services at more than 100 hospitals throughout the United States.

Cogent Healthcare Inc., based in Brentwood, Tenn., recently announced Dean Weiland as the private hospitalist staffing company’s new president and CEO. Weiland served as an executive during a merger between Renal Advantage and Liberty Dialysis in 2010. Before that, he served as CEO of The Work Institute.

Hill Country Memorial Hospital (HCM) in Fredericksburg, Texas, has announced plans to expand its 24-hour hospitalist service from only weekends to seven days a week. The decision comes as a reaction to the positive benefits HCM has experienced since it began its weekend hospitalist service in 2011.

Hospitalist Robert McNab, DO, has been named the new medical education director of Freeman Health System in Joplin, Mo. He will continue as a hospitalist and director of the internal-medicine residency program. Dr. McNab brings more than 10 years of teaching experience to the Freeman Graduate Medical Education Program.

Brian Harte, MD, SFHM, Cleveland Clinic hospitalist and president of South Pointe Hospital in Warrensville Heights, Ohio, is now president of Hillcrest Hospital in Mayfield Heights, Ohio. Dr. Harte is an SHM board member and serves as the board treasurer. In addition to his new role, Dr. Harte will continue to practice as a hospitalist at Hillcrest Hospital.

Anita Dhople, MD, is the new hospitalist medical director for the Rockledge, Fla.-based Health First health system. Dr. Dhople will oversee all hospitalist services at four affiliated hospitals. Dr. Dhople comes to Health First from the Piedmont Physicians Group in Atlanta.

Matthew Heinz, MD, has been appointed director of provider outreach in the U.S. Department of Health and Human Services’ Office of Intergovernmental and External Affairs (IEA). Dr. Heinz is a practicing hospitalist at Tucson (Ariz.) Medical Center and a former representative in the Arizona state legislature.

Business Moves

IPC: The Hospitalist Company, based in North Hollywood, Calif., has announced the acquisition of two private hospitalist practices: Sound Senior Geriatrics LLC (SSG) in Mystic, Conn., and Cape Coral Hospitalists Inc. (CCH) based in Fort Meyers, Fla. IPC contracts hospitalist services in 28 states.

Bayhealth hospital network in Dover, Del., has partnered with Apogee Physicians to provide 24-hour hospitalist services at Kent General Hospital in Dover and Milford Memorial Hospital in Milford. Bayhealth has been serving communities in central and southern Delaware for more than 75 years. Phoenix-based Apogee Physicians has been providing contracted hospitalist services since 2002.

Cogent Healthcare is partnering with South Georgia Medical Center (SGMC) to provide hospitalist services at the 285-bed acute-care nonprofit main campus and the 55-bed Smith Northview Campus in Valdosta, Ga. SGMC currently serves 15 counties in south-central Georgia and north Florida. Cogent provides contracted hospitalist services at more than 100 hospitals throughout the United States.

Cogent Healthcare Inc., based in Brentwood, Tenn., recently announced Dean Weiland as the private hospitalist staffing company’s new president and CEO. Weiland served as an executive during a merger between Renal Advantage and Liberty Dialysis in 2010. Before that, he served as CEO of The Work Institute.

Hill Country Memorial Hospital (HCM) in Fredericksburg, Texas, has announced plans to expand its 24-hour hospitalist service from only weekends to seven days a week. The decision comes as a reaction to the positive benefits HCM has experienced since it began its weekend hospitalist service in 2011.

Hospitalist Robert McNab, DO, has been named the new medical education director of Freeman Health System in Joplin, Mo. He will continue as a hospitalist and director of the internal-medicine residency program. Dr. McNab brings more than 10 years of teaching experience to the Freeman Graduate Medical Education Program.

Brian Harte, MD, SFHM, Cleveland Clinic hospitalist and president of South Pointe Hospital in Warrensville Heights, Ohio, is now president of Hillcrest Hospital in Mayfield Heights, Ohio. Dr. Harte is an SHM board member and serves as the board treasurer. In addition to his new role, Dr. Harte will continue to practice as a hospitalist at Hillcrest Hospital.

Anita Dhople, MD, is the new hospitalist medical director for the Rockledge, Fla.-based Health First health system. Dr. Dhople will oversee all hospitalist services at four affiliated hospitals. Dr. Dhople comes to Health First from the Piedmont Physicians Group in Atlanta.

Matthew Heinz, MD, has been appointed director of provider outreach in the U.S. Department of Health and Human Services’ Office of Intergovernmental and External Affairs (IEA). Dr. Heinz is a practicing hospitalist at Tucson (Ariz.) Medical Center and a former representative in the Arizona state legislature.

Business Moves

IPC: The Hospitalist Company, based in North Hollywood, Calif., has announced the acquisition of two private hospitalist practices: Sound Senior Geriatrics LLC (SSG) in Mystic, Conn., and Cape Coral Hospitalists Inc. (CCH) based in Fort Meyers, Fla. IPC contracts hospitalist services in 28 states.

Bayhealth hospital network in Dover, Del., has partnered with Apogee Physicians to provide 24-hour hospitalist services at Kent General Hospital in Dover and Milford Memorial Hospital in Milford. Bayhealth has been serving communities in central and southern Delaware for more than 75 years. Phoenix-based Apogee Physicians has been providing contracted hospitalist services since 2002.

Cogent Healthcare is partnering with South Georgia Medical Center (SGMC) to provide hospitalist services at the 285-bed acute-care nonprofit main campus and the 55-bed Smith Northview Campus in Valdosta, Ga. SGMC currently serves 15 counties in south-central Georgia and north Florida. Cogent provides contracted hospitalist services at more than 100 hospitals throughout the United States.

Cogent Healthcare Inc., based in Brentwood, Tenn., recently announced Dean Weiland as the private hospitalist staffing company’s new president and CEO. Weiland served as an executive during a merger between Renal Advantage and Liberty Dialysis in 2010. Before that, he served as CEO of The Work Institute.

Hill Country Memorial Hospital (HCM) in Fredericksburg, Texas, has announced plans to expand its 24-hour hospitalist service from only weekends to seven days a week. The decision comes as a reaction to the positive benefits HCM has experienced since it began its weekend hospitalist service in 2011.

With a record number of attendees, Pediatric Hospital Medicine 2013 (PHM) swept into New Orleans last month, carrying with it unbridled enthusiasm about the past, present, and future.

Virginia Moyer, MD, MPH, vice president for maintenance of certification and quality for the American Board of Pediatrics (ABP) and professor of pediatrics and chief of academic general pediatrics at Texas Children’s Hospital, delivered a keynote address to 700 attendees that focused on the challenges and opportunities of providing evidence-based, high-quality care in the hospital, as well as ABP’s role in meeting these challenges.

“If evidence-based medicine is an individual sport,” Dr. Moyer said, “then quality improvement is a team sport.”

Barriers to quality improvement (QI)— such as lack of will, lack of data, and lack of training—can be surmounted in a team environment, she said. ABP is continuing in its efforts to support QI education through its Maintenance of Certification (MOC) Part 4 modules, as well as other educational activities.

Other highlights of the 10th annual Pediatric Hospital Medicine meeting:

• The addition of a new “Community Hospitalists” track was given high marks by those in attendance. It covered such topics as perioperative management of medically complex pediatric patients, community-acquired pneumonia, and osteomyelitis.
• A 10-year retrospective of pediatric hospital medicine was given by a panel of notable pediatric hospitalists, including Erin Stucky Fisher, MD, FAAP, MHM, chief of hospital medicine at Rady Children’s Hospital in San Diego; Mary Ottolini, MD, MPH, chief of hospital medicine at Children’s National Medical Center in Washington; Jack Percelay, MD, MPH, FAAP, associate clinical professor at Pace University; and Daniel Rauch, MD, FAAP, pediatric hospitalist program director at the NYU School of Medicine in New York City. A host of new programs has been established by the PHM community, including the Quality Improvement Innovation Networks (QuIIN); the Value in Pediatrics (VIP) network; the International Network for Simulation-Based Pediatric Innovation, Research, and Education (INSPIRE); patient- and family-centered rounds; and the I-PASS Handoff Program. The panel also discussed future challenges, including reduction of unnecessary treatments, interfacing, and perhaps incorporating “hyphen hospitalists,” and learning from advances made by the adult HM community.
• The ever-popular “Top Articles in Pediatric Hospital Medicine” session was presented by H. Barrett Fromme, MD, associate professor of pediatrics at the University of Chicago, and Ben Bauer, MD, director of pediatric hospital medicine at Riley Hospital for Children at Indiana University Health in Indianapolis, which was met with raucous approval by the audience. The presentation not only educated those in attendance about the most cutting-edge pediatric literature, but it also included dance moves most likely to attract the opposite sex and clothing appropriate for the Australian pediatric hospitalist.
• The three presidents of the sponsoring societies—Thomas McInerney, MD, FAAP, of the American Academy of Pediatrics, David Keller, MD, of the Academic Pediatric Association, and Eric Howell, MD, SFHM, of SHM—presented each society’s contributions to the growth of PHM, as well as future areas for cooperative sponsorship. These include the development of the AAP Section of Hospital Medicine Library website (sohmlibrary.org), the APA Quality Scholars program, and SHM’s efforts to increase interest in hospital medicine in medical students and trainees. “Ask not what hospital medicine can do for you,” Dr. Howell implored, “ask what you can do for hospital medicine!”
• Members of the Joint Council of Pediatric Hospital Medicine (JCPHM) presented the recent recommendations of the council arising from an April 2013 meeting with the ABP in Chapel Hill, N.C. Despite acknowledgements that no decision will be met with uniform satisfaction by all the stakeholders, the JCPHM concluded that the path that would best advance the field of PHM, provide for high-quality care of hospitalized children, and ensure the public trust would be a two-year fellowship sponsored by ABP. This would ultimately lead to approved certification eligibility for fellowship graduates by the American Board of Medical Specialties (ABMS); it would also make provisions for “grandfathering” in current pediatric hospitalists. Concerns from med-peds, community hospitalists, and recent residency graduate communities were addressed by the panel.
• A recurrent theme of reducing unnecessary treatments, interventions, and, perhaps, hospitalizations was summarized eloquently by Alan Schroeder, MD, director of the pediatric ICU and chief of pediatric inpatient care at Santa Clara (Calif.) Valley Health. Barriers to reducing unnecessary care can be substantial, including pressure from families, pressure from colleagues, profit motive, and the “n’s of 1,” according to Dr. Schroeder. Ultimately, however, avoiding testing and treatments that have no benefit to children will improve care. “Ask, ‘How will this test benefit my patient?’ not ‘How will this test change management?’” Dr. Schroeder advised.

Dr. Chang is The Hospitalist’s pediatric editor and a med-peds-trained hospitalist working at the University of California San Diego and Rady Children’s Hospital.

With a record number of attendees, Pediatric Hospital Medicine 2013 (PHM) swept into New Orleans last month, carrying with it unbridled enthusiasm about the past, present, and future.

Virginia Moyer, MD, MPH, vice president for maintenance of certification and quality for the American Board of Pediatrics (ABP) and professor of pediatrics and chief of academic general pediatrics at Texas Children’s Hospital, delivered a keynote address to 700 attendees that focused on the challenges and opportunities of providing evidence-based, high-quality care in the hospital, as well as ABP’s role in meeting these challenges.

“If evidence-based medicine is an individual sport,” Dr. Moyer said, “then quality improvement is a team sport.”

Barriers to quality improvement (QI)— such as lack of will, lack of data, and lack of training—can be surmounted in a team environment, she said. ABP is continuing in its efforts to support QI education through its Maintenance of Certification (MOC) Part 4 modules, as well as other educational activities.

Other highlights of the 10th annual Pediatric Hospital Medicine meeting:

• The addition of a new “Community Hospitalists” track was given high marks by those in attendance. It covered such topics as perioperative management of medically complex pediatric patients, community-acquired pneumonia, and osteomyelitis.
• A 10-year retrospective of pediatric hospital medicine was given by a panel of notable pediatric hospitalists, including Erin Stucky Fisher, MD, FAAP, MHM, chief of hospital medicine at Rady Children’s Hospital in San Diego; Mary Ottolini, MD, MPH, chief of hospital medicine at Children’s National Medical Center in Washington; Jack Percelay, MD, MPH, FAAP, associate clinical professor at Pace University; and Daniel Rauch, MD, FAAP, pediatric hospitalist program director at the NYU School of Medicine in New York City. A host of new programs has been established by the PHM community, including the Quality Improvement Innovation Networks (QuIIN); the Value in Pediatrics (VIP) network; the International Network for Simulation-Based Pediatric Innovation, Research, and Education (INSPIRE); patient- and family-centered rounds; and the I-PASS Handoff Program. The panel also discussed future challenges, including reduction of unnecessary treatments, interfacing, and perhaps incorporating “hyphen hospitalists,” and learning from advances made by the adult HM community.
• The ever-popular “Top Articles in Pediatric Hospital Medicine” session was presented by H. Barrett Fromme, MD, associate professor of pediatrics at the University of Chicago, and Ben Bauer, MD, director of pediatric hospital medicine at Riley Hospital for Children at Indiana University Health in Indianapolis, which was met with raucous approval by the audience. The presentation not only educated those in attendance about the most cutting-edge pediatric literature, but it also included dance moves most likely to attract the opposite sex and clothing appropriate for the Australian pediatric hospitalist.
• The three presidents of the sponsoring societies—Thomas McInerney, MD, FAAP, of the American Academy of Pediatrics, David Keller, MD, of the Academic Pediatric Association, and Eric Howell, MD, SFHM, of SHM—presented each society’s contributions to the growth of PHM, as well as future areas for cooperative sponsorship. These include the development of the AAP Section of Hospital Medicine Library website (sohmlibrary.org), the APA Quality Scholars program, and SHM’s efforts to increase interest in hospital medicine in medical students and trainees. “Ask not what hospital medicine can do for you,” Dr. Howell implored, “ask what you can do for hospital medicine!”
• Members of the Joint Council of Pediatric Hospital Medicine (JCPHM) presented the recent recommendations of the council arising from an April 2013 meeting with the ABP in Chapel Hill, N.C. Despite acknowledgements that no decision will be met with uniform satisfaction by all the stakeholders, the JCPHM concluded that the path that would best advance the field of PHM, provide for high-quality care of hospitalized children, and ensure the public trust would be a two-year fellowship sponsored by ABP. This would ultimately lead to approved certification eligibility for fellowship graduates by the American Board of Medical Specialties (ABMS); it would also make provisions for “grandfathering” in current pediatric hospitalists. Concerns from med-peds, community hospitalists, and recent residency graduate communities were addressed by the panel.
• A recurrent theme of reducing unnecessary treatments, interventions, and, perhaps, hospitalizations was summarized eloquently by Alan Schroeder, MD, director of the pediatric ICU and chief of pediatric inpatient care at Santa Clara (Calif.) Valley Health. Barriers to reducing unnecessary care can be substantial, including pressure from families, pressure from colleagues, profit motive, and the “n’s of 1,” according to Dr. Schroeder. Ultimately, however, avoiding testing and treatments that have no benefit to children will improve care. “Ask, ‘How will this test benefit my patient?’ not ‘How will this test change management?’” Dr. Schroeder advised.

Dr. Chang is The Hospitalist’s pediatric editor and a med-peds-trained hospitalist working at the University of California San Diego and Rady Children’s Hospital.

With a record number of attendees, Pediatric Hospital Medicine 2013 (PHM) swept into New Orleans last month, carrying with it unbridled enthusiasm about the past, present, and future.

Virginia Moyer, MD, MPH, vice president for maintenance of certification and quality for the American Board of Pediatrics (ABP) and professor of pediatrics and chief of academic general pediatrics at Texas Children’s Hospital, delivered a keynote address to 700 attendees that focused on the challenges and opportunities of providing evidence-based, high-quality care in the hospital, as well as ABP’s role in meeting these challenges.

“If evidence-based medicine is an individual sport,” Dr. Moyer said, “then quality improvement is a team sport.”

Barriers to quality improvement (QI)— such as lack of will, lack of data, and lack of training—can be surmounted in a team environment, she said. ABP is continuing in its efforts to support QI education through its Maintenance of Certification (MOC) Part 4 modules, as well as other educational activities.

Other highlights of the 10th annual Pediatric Hospital Medicine meeting:

• The addition of a new “Community Hospitalists” track was given high marks by those in attendance. It covered such topics as perioperative management of medically complex pediatric patients, community-acquired pneumonia, and osteomyelitis.
• A 10-year retrospective of pediatric hospital medicine was given by a panel of notable pediatric hospitalists, including Erin Stucky Fisher, MD, FAAP, MHM, chief of hospital medicine at Rady Children’s Hospital in San Diego; Mary Ottolini, MD, MPH, chief of hospital medicine at Children’s National Medical Center in Washington; Jack Percelay, MD, MPH, FAAP, associate clinical professor at Pace University; and Daniel Rauch, MD, FAAP, pediatric hospitalist program director at the NYU School of Medicine in New York City. A host of new programs has been established by the PHM community, including the Quality Improvement Innovation Networks (QuIIN); the Value in Pediatrics (VIP) network; the International Network for Simulation-Based Pediatric Innovation, Research, and Education (INSPIRE); patient- and family-centered rounds; and the I-PASS Handoff Program. The panel also discussed future challenges, including reduction of unnecessary treatments, interfacing, and perhaps incorporating “hyphen hospitalists,” and learning from advances made by the adult HM community.
• The ever-popular “Top Articles in Pediatric Hospital Medicine” session was presented by H. Barrett Fromme, MD, associate professor of pediatrics at the University of Chicago, and Ben Bauer, MD, director of pediatric hospital medicine at Riley Hospital for Children at Indiana University Health in Indianapolis, which was met with raucous approval by the audience. The presentation not only educated those in attendance about the most cutting-edge pediatric literature, but it also included dance moves most likely to attract the opposite sex and clothing appropriate for the Australian pediatric hospitalist.
• The three presidents of the sponsoring societies—Thomas McInerney, MD, FAAP, of the American Academy of Pediatrics, David Keller, MD, of the Academic Pediatric Association, and Eric Howell, MD, SFHM, of SHM—presented each society’s contributions to the growth of PHM, as well as future areas for cooperative sponsorship. These include the development of the AAP Section of Hospital Medicine Library website (sohmlibrary.org), the APA Quality Scholars program, and SHM’s efforts to increase interest in hospital medicine in medical students and trainees. “Ask not what hospital medicine can do for you,” Dr. Howell implored, “ask what you can do for hospital medicine!”
• Members of the Joint Council of Pediatric Hospital Medicine (JCPHM) presented the recent recommendations of the council arising from an April 2013 meeting with the ABP in Chapel Hill, N.C. Despite acknowledgements that no decision will be met with uniform satisfaction by all the stakeholders, the JCPHM concluded that the path that would best advance the field of PHM, provide for high-quality care of hospitalized children, and ensure the public trust would be a two-year fellowship sponsored by ABP. This would ultimately lead to approved certification eligibility for fellowship graduates by the American Board of Medical Specialties (ABMS); it would also make provisions for “grandfathering” in current pediatric hospitalists. Concerns from med-peds, community hospitalists, and recent residency graduate communities were addressed by the panel.
• A recurrent theme of reducing unnecessary treatments, interventions, and, perhaps, hospitalizations was summarized eloquently by Alan Schroeder, MD, director of the pediatric ICU and chief of pediatric inpatient care at Santa Clara (Calif.) Valley Health. Barriers to reducing unnecessary care can be substantial, including pressure from families, pressure from colleagues, profit motive, and the “n’s of 1,” according to Dr. Schroeder. Ultimately, however, avoiding testing and treatments that have no benefit to children will improve care. “Ask, ‘How will this test benefit my patient?’ not ‘How will this test change management?’” Dr. Schroeder advised.

Dr. Chang is The Hospitalist’s pediatric editor and a med-peds-trained hospitalist working at the University of California San Diego and Rady Children’s Hospital.

Back to the Furture Past RIV winners talk about what the recognition meant for their careers By Larry Beresford

Twylla Tassava, MD

After winning SHM’s annual Research, Innovations, and Clinical Vignettes (RIV) scientific abstract and poster competition for an abstract illustrating a program that promoted flu vaccinations for families of neonatal patients, Shetal Shah, MD, FAAP, became a leading advocate for two laws mandating that New York hospitals offer vaccinations to families.

A poster that described a VTE prevention program led Gregory Maynard, MD, MSc, SFHM, to join SHM’s VTE Prevention Collaborative and, eventually, to become senior vice president of the society’s Center for Hospital Innovation and Improvement.

A prize-winning innovations poster for improving team communication by Vineet Chopra, MD, MS, FACP, FHM, and colleagues later took off as a new technology company.

Leonard Feldman, MD, FAAP, SFHM, won for a poster that explained online CME curriculum for hospitalists as consultants; the curriculum now resides on SHM’s website.

The evidence is clear: RIV abstracts are a vital part of hospital medicine.

Nearly 800 abstracts were submitted for HM13.

Awards are given in three categories:

• Research posters report clinical or basic science data, systematically review a clinical problem, or address efficiency, cost, or method of health-care delivery or medical decision-making;
• Innovations posters describe an existing innovative program in hospital medicine, often with preliminary data; and
• Clinical vignettes, either adult or pediatric, report on one or more cases illustrating a new disease entity, a prominent or unusual feature of an established disease, or an area of clinical controversy.

The Hospitalist asked 11 past RIV winners what the poster contest meant to their careers. Some added more data and analysis and went on to be published in such medical journals as the Journal of Hospital Medicine. Some used the recognition to launch or boost research-oriented careers; others saw their careers go in different directions.

“Winning a national poster competition gives you the confidence to continue to pursue your interest and take it to a higher level, like successfully competing for funding and publishing your line of inquiry,” says hospitalist and researcher Vineet Arora, MD, MPP, FHM, of the University of Chicago, who won the 2006 RIV research competition. “Sometimes, presenting posters can be lonely, but at SHM, you get a lot of traffic. You get a chance to practice your spiel, communicating science and research in a very concise way, which is an important skill to have.”

David Metzger, MD, PhD, also from the University of Chicago, who won the RIV research award in 2005, says recognition is a big deal, but “one of the biggest values of the RIV competition is just getting information out to colleagues, with the opportunity to talk with your peers. That’s the real prize.

“I’ve been involved in presenting posters at SHM every year that the society has been in existence,” he says. “I’ve met so many people and talked about what they’re doing. That’s what a medical society should do—bring people together like this.”

Twylla Tassava, MD

Title: Administrator, academic consult service; teaching staff physician

Institution: Saint Joseph Mercy Hospital, Ypsilanti, Mich.

Year: 2008

RIV: “A Case of Salty Voluminous Urine” (clinical vignette)

Dr. Tassava was honored two years in a row for topics drawn from her experience as a hospitalist working in the surgical ICU. Her HM08 entry won top poster, and her HM09 poster, “Permissive Hypernatremia: Co-Management of Intracranial Pressure in a Patient with Diabetes Insipidus,” was selected for an oral presentation.

The HM09 vignette described how the hypernatremia that occurs with diabetes insipidus could be used in a novel way to control intracranial pressure in a 17-year-old patient who had a traumatic brain injury from an auto accident.

“She had a beautiful outcome,” Dr. Tassava says. “She started college and she came back to our unit for a visit after her recovery.”

Dr. Tassava enjoyed the opportunity to explain to her peers how diabetes insipidus presented and how she managed the case. “I was a little surprised at how much discussion was generated by my case,” she says, “even though I knew this was an important and novel approach.”

When her hospital added intensivists, her work and research in the ICU ended and her career moved more toward hospitalist administration. She now runs the academic consult service at St. Joseph, serves as lead physician for the orthopedic surgery floor, instructs and mentors medical residents, and chairs the hospital’s Coagulation Collaborative Practice Team (Coagulation CPT). She credits the RIV honors with helping her to gain recognition as an academic hospitalist who was nominated for leadership roles. She has moved out of research for now but plans to pursue anticoagulation research in the future.

“I really appreciated the recognition for my curiosity and scientific approach, which was acknowledged by my surgical colleagues,” Dr. Tassava says. “I absolutely love the CPT. I am the hospital’s principal educator with regard to anticoagulation. Over the past year, I have given medicine and cardiology grand rounds, and have presented on the newest anticoagulants.”

Dr. Tassava still collaborates with her residents on abstracts, several of which have been submitted to SHM, the American College of Physicians, and other medical societies.

“I still love research,” she says. “I have a million ideas.”

Gregory Maynard, MD, MSc, SFHM

Title: Chief of the division of hospital medicine; senior vice president, SHM’s Center for Innovation and Improvement

Institution: University of California at San Diego (UCSD)

Year: 2008

RIV: “Prevention of Hospital-Acquired Venous Thromboembolism: Prospective Validation of a VTE Risk Assessment Model and Protocol” (research)

Citations: Maynard G, Stein J. Designing and implementing effective VTE prevention protocols: lessons from collaboratives. J Thromb Thrombolysis. 2010;29(2):159-166. Maynard G, Morris T, Jenkins I, et al. Optimizing prevention of hospital acquired venous thromboembolism: prospective validation of a VTE risk assessment model. J Hosp Med. 2010;5(1):10-18.

Dr. Maynard’s abstract described a project funded by the federal Agency for Healthcare Research and Quality to design and implement an organized, comprehensive protocol for VTE prevention within the hospital setting. The project also included a toolkit to help other hospitals do the same thing. The same group received SHM’s Award of Excellence for Teamwork.

This work, combined with similar efforts by Jason Stein, MD, and colleagues at Emory University in Atlanta and others, provided the foundation for SHM’s VTE resource room and the mentored implementation program of SHM’s VTE Prevention Collaborative, which had been launched in 2007 as one of the society’s first large-scale quality-improvement (QI) initiatives.

“SHM wanted to do something about VTE prevention, and when we got our AHRQ grant, I was interested in doing the same,” Dr. Maynard says. “We published our implementation guides on the AHRQ and SHM websites, along with a lot of valuable supporting materials.”

Dr. Maynard later took on leadership roles with SHM’s quality initiatives on glycemic control and care transitions, which made him the logical choice to become senior vice president of SHM’s Center for Hospital Innovation and Improvement.

He says the RIV honor lifted his profile not only within SHM, but also throughout the field, and it was instrumental in obtaining continued funding to advance the VTE initiative. “We did this tremendous work—with great results,” he says. “But I don’t think our local administrators appreciated it quite as much until we started to get external, national recognition.”

Dr. Maynard earned his master’s degree in biostatistics and clinical research design from the University of Michigan—skills he later brought to the academic setting at UCSD.

“It was a nice way for a hospitalist, who’s really a medical generalist, to become an expert in something,” he says. “I could never be more of an expert in cardiology than a cardiologist, or more of an expert in DVT than a hematologist or critical-care specialist. But I could help both of them do what they couldn’t do as effectively, which was to implement protocols reliably using a QI framework.”

Eduard E. Vasilevskis, MD

Title: Assistant professor of general internal medicine, hospital medicine, and public health

Institution: Vanderbilt University, Nashville, Tenn.

Year: 2009

RIV: “Predictors of Early Post-Discharge Mortality in Critically Ill Patients: Lessons for Quality Performance and Quality Assessment” (research)

Citation: Vasilevskis EE, Kuzniewicz MW, Cason BA, et al. Predictors of early post-discharge mortality in critically ill patients: a retrospective cohort study from the California Intensive Care Outcomes project. J Crit Care. 2011;26(1):65-75.

Dr. Vasilevskis has submitted abstracts to the RIV competition almost every year since 2007, when he was completing a fellowship at the University of California at San Francisco’s Institute for Health Policy Studies. He was honored in 2009 for a project based on the California Intensive Care Outcomes Project, which drew data from 35 hospitals to demonstrate that shortening ICU length of stay was predictive of early post-discharge mortality in the most severely ill patients.

He has continued to research quality and safety in the ICU, and he has published dozens of journal articles.

“My initial focus was on traditional mortality and length-of-stay outcomes,” he says. “I am now pursuing additional outcomes, most notably delirium in the ICU patient. I work with an amazing group of researchers that are trying to better measure, define, and treat delirium in the ICU—an outcome associated with a number of poor patient outcomes.”

Dr. Vasilevskis also is researching the causes of hospital readmissions and the development of novel ways to improve care transitions for elderly patients. He is pursuing a master’s of public health at Vanderbilt, and is co-principal investigator of an investigation of the Hospital Medicine Reengineering Network to improve transitions of care, supported by the Association of American Medical Colleges.

In addition to his 2009 win, he captured the HM10 and HM12 research categories. His HM12 poster, “Veterans Administration Acute Care 30-Day Mortality Model: Development, Validation and Performance Variation,” was singled out by the judging committee for its impressive sample size (1,114,327 patients in a retrospective cohort study of 131 VA hospitals), as well as for how it combined administrative and clinical risk models.

Dr. Vasilevskis says the opportunity to present his research at SHM and the recognition he received encouraged him to continue as a hospitalist engaged in medical research. He has been a member of SHM’s Research Committee since 2009, an RIV judge at HM11, and chaired the HM13 RIV competition subcommittee.

Vineet Chopra, MD, MS, FACP, FHM

Title: Assistant professor of medicine

Institution: University of Michigan Health System, Ann Arbor

Year: 2009

RIV: “MComm: Redefining Medical Communications in the 21st Century” (innovations)

Early in his career, Dr. Chopra was curious about how to improve the way patient care is delivered in the hospital setting. He was particularly interested in the inordinate amount of time hospitalists spend every day on communication.

“I saw one-way paging systems as a problem for communication between members of the medical team,” he says. “Doctors get paged and break off from what they’re doing to return the page—to someone who often isn’t there to take the call back. Sometimes the system gives us the wrong number or a cryptic message that makes no sense.”

A technological solution to this problem, which he and hospitalist Prasanth Gogineni, MD, conceived, designed, and created, then tested at the University of Michigan, is called MComm. Dr. Chopra describes it as a novel, uniform way of messaging for the entire medical team using wireless servers, PUSH technology, and iPhones. MComm was built around existing hospital workflow and patient-specific task lists, assigning priority to each message and documenting that it was delivered. The junior faculty members submitted an abstract about their innovative application, not really expecting it to get accepted. But when it won the poster competition and was selected for a plenary presentation, things got busy in a hurry. Specifically, the university hospital’s Office of Technology Transfer took a keen interest.

“We met with a number of people who had business experience in the health-care-technology space and found a CEO for the company we formed to develop MComm,” Dr. Chopra says. “I found myself getting pulled into it very quickly, with a lot of conversations about commercialization, revenue-sharing models, intellectual property, and the like.”

But running a company was not something Dr. Chopra wanted to do. Two years ago, that company, Synaptin, went one way and he went another—he stayed at Michigan as a medical researcher. He remains deeply interested in how care is delivered to hospitalized patients, but with a focus on such patient-safety questions as how to prevent negative outcomes from indwelling venous catheters.

“Winning the poster competition opened doors for me—there’s no doubt in my mind,” he says. “We demonstrated the ability to deliver a project of significance, from concept to prototype, without formal training in this area. If we didn’t have that recognition, I’m not sure I would have been ready to step into a research career as quickly. It helped me realize that medical research was what I wanted to do.”

Vineet Arora, MD, MPP, FHM

Title: Associate program director, internal-medicine residency; assistant dean of scholarship and discovery

Institution: Pritzker School of Medicine, University of Chicago

Year: 2006

RIV: “Measuring Quality of Hospital Care for Vulnerable Elders: Use of ACOVE Quality Indicators” (research)

Citation: Arora VM, Fish M, Basu A, et al. Relationship between quality of care of hospitalized vulnerable elders and postdischarge mortality. J Am Geriatrics. 2010;58:1642-1648.

David O. Meltzer, MD, PhD

Title: Associate professor, department of medicine; associate faculty member, Harris School and the Department of Economics

Institution: University of Chicago

Year: 2005

RIV: “Effects of Hospitalists on Outcomes and Costs in a Multicenter Trial of Academic Hospitalists” (research)

Dr. Meltzer was the lead author, with 11 other prominent hospitalists, of an abstract based on a multisite study of the cost and outcome implications of the hospitalist model—still a relatively new concept in 2001, when the research began. Although the study did not uncover large cost savings realized from the hospitalist model of care, as some advocates had hoped, important findings and implications for the emerging field were teased out of the data.

At the time, only a few randomly controlled, multisite studies of costs and outcomes for the hospitalist model had been performed. The study, Dr. Meltzer says, required a complicated analysis to discover that hospitalists, in fact, saved their facilities money, with their most important impact realized post-hospitalization, such as on nursing-home costs. It was important to control for spillover effect and the fact that hospitalists do a better job of teaching house staff, while a physician’s years of experience was another important variable, he says.

Dr. Meltzer was a medical researcher interested in medical specialization when the term “hospitalist” was first coined in 1996. “I thought, here was a chance to study a medical specialty in its formative stages,” he says.

He still works as a hospitalist, although with limited clinical time. In addition to his administrative work as division chief, he directs the Center for Health and the Social Sciences at the University of Chicago. His research interests include cost-effectiveness, technology assessment, and information research.

In 2010, his poster “Effects of Hospitalists on 1-Year Post-Discharge Resource Utilization by Medicare Beneficiaries” took the top prize in the HM10 research competition. In 2011, he was appointed to the methodology committee of the federal Patient-Centered Outcomes Research Institute (PCORI), which was created by the Affordable Care Act to advise the government on clinical-effectiveness research. He also sits on the Advisory Council to the National Institute of General Medical Sciences at the Institute of Medicine, and on the Congressional Budget Office’s panel of health advisors.

In a career full of recognition, Dr. Meltzer says it’s hard to pinpoint the impact of winning the poster contest. But he has continued to submit abstracts to SHM every year and appreciates the opportunities for interaction with peers at the poster exhibits.

Paul J. Grant, MD, FACP, SFHM

Title: Director of perioperative and consultative medicine

Institution: University of Michigan, Ann Arbor

Year: 2006

RIV: “Disseminated Histoplasmosis Presenting As Painful Oral Ulcers” (clinical vignettes)

Dr. Grant’s winning vignette presented a patient with a complex medical history, including heart disease and four months of painful oral ulcers, for which prior evaluations had been inconclusive, despite conducting biopsies. Following administration of high-dose corticosteroids, the patient’s condition worsened on multiple fronts. The vignette showed how the medical team was able to diagnose an unusual presentation of a fungal infection called histoplasmosis, which is prevalent in parts of the Midwest surrounding the Ohio and Mississippi river valleys.

“We see a lot of cases in the hospital where there are different angles you could take to turn it into a clinical vignette or a nice poster with good teaching points,” Dr. Grant says. “In this case, just digging deeper into the actual diagnosis was important because the empiric use of steroids can be fatal for some patients. Steroids are given for a lot of good reasons, but in this patient they caused immune suppression, allowing a smoldering infection to become very active.”

Dr. Grant did not submit the vignette for publication. “That was probably a mistake on my part,” he says, acknowledging the common complaint of too little time and too many competing priorities. But his interest in research has continued.

“I became involved at a national level with issues of perioperative medicine and last August published a textbook on the subject,” he reports.¹ “VTE is another area of interest I have developed since my hospital medicine fellowship.”

He serves as the VTE resource expert on the Michigan Hospital Medicine Safety Consortium, a quality collaborative of more than 40 hospitals with Blue Cross/Blue Shield of Michigan. “It’s exciting to be able to look at the risk factors, what kinds of patients get VTEs, and whether they were appropriately prophylaxed in the hospital,” he says.

VTE is a national quality priority, and Dr. Grant expects abstracts to emerge from the consortium’s work.

He says he appreciates the opportunities that arise from participating in poster sessions at SHM, where medical students, residents, and working hospitalists talk to the presenters of interesting cases.

“It gives you a real back-and-forth, which is good for the person asking the question and for the presenter,” he says, noting hospitalists from other parts of the country were not as familiar with histoplasmosis.

He says winning the HM06 poster contest helped him “get his feet wet” and feel more prepared for a career in academic hospital medicine. “I’m sure the award solidified my employers’ satisfaction in hiring me—and in giving me more desirable academic roles and responsibilities,” he adds.

Leonard Feldman, MD, FACP, FAAP, SFHM

Title: Assistant professor of medicine pediatrics; director of the general internal-medicine comprehensive consultation service

Institution: Johns Hopkins Hospital, Baltimore

Year: 2009

RIV: “An Internet-Based Consult Curriculum for Hospitalists” (innovations)

Dr. Feldman’s poster described an online CME curriculum for hospitalists acting as medical consultants. The concept grew out of a perceived deficiency in his own medical education when, in 2004, he was asked to lead the consultation service at Johns Hopkins—just six months after finishing his residency.

“I had no idea what I was doing as a general-internal-medicine consultant,” he says. “I maybe received two weeks of experience as a consultant during my residency. I was willing to take it on, learning on the job and asking for help. But it occurred to me that I’m probably not alone in feeling unprepared.”

In his quest for self-education, Dr. Feldman wondered whether he should write a textbook on the subject. “But the information changes so quickly, I thought I’d have a better chance to reach people online,” he notes.

After talking to publishers and CME companies, he came up with the concept of learning modules on perioperative and consultative medicine topics, which could be taken online while earning CME credits. Johns Hopkins served as the CME certifier, and medical-education company Advanced Studies in Medicine joined as a partner. Once the project got off the ground, a medical advisory committee was convened.

“Winning the SHM poster competition is a great honor to have on a CV. It really helps to legitimize your name in the world of hospital medicine,” Dr. Feldman says. “It also provided confirmation that we were on the right track with the curriculum project. People valued what we were doing.”

Dr. Feldman and SHM have since become affiliated, and the “Consultative and Perioperative Medicine Essentials for Hospitalists” modules are available on SHM’s website (www.shmconsults.com). The site has 12,000 registered members completing 500 CME modules every month.

“I do a lot of the editing still,” Dr. Feldman says. “We update the modules every two years and are still creating new ones.”

Dr. Feldman also pursues a number of clinical-research interests, including resident education and costs of care.

Kristin Wise, MD, FHM

Title: Assistant professor of medicine

Institution: Medical University of South Carolina, Charleston

Year: 2009

RIV: “Intensivists versus Hospitalists in the ICU: A Prospective Cohort Study Comparing Mortality and Length of Stay Between Two Staffing Models” (research) Citation: Wise KR, Akopov VA, Williams BR, Ido MS, Leeper KV, Dressler DD. Hospitalists and intensivists in the medical ICU: a prospective and observational study comparing mortality and length of stay between two staffing models. J Hosp Med. 2012;7(3):183-189.

Dr. Wise was recognized for research that began while she worked at Emory University in Atlanta, comparing hospitalists and intensivists in such outcomes as length of stay and mortality rates for patients in the ICU. The study was one of the first statistically rigorous examinations of this critical quality question. With an eye toward improving patient safety, national quality advocates such as the Leapfrog Group have called for hospitals to employ intensivists (critical-care specialists) to manage the care of ICU patients. In reality, Dr. Wise says, there aren’t enough intensivists to meet the need.

“Hospitalists are in the ICU anyway,” she says. “We just don’t have enough data to answer how well they do [in comparison to intensivists].”

Through a prospective cohort study of more than 1,000 patients, Dr. Wise’s group found that there was essentially no statistical difference in mortality rates between patients treated by intensivist teams or hospitalist ICU teams.

“We were also able to look at some of the intermediate-acuity patients—fairly complicated but not requiring ventilators,” she explains. “Our study wasn’t sufficiently powered for this subgroup, but it was an interesting piece of data to raise the question: Where should we deploy this scarce resource of intensivists? Which pockets of patients?”

Presenting her abstract at SHM’s annual meeting was a “good experience.”

“I’d done public speaking before, but never with an audience of about 500 people,” she says. “To go out there and field their questions was a real professional growing experience. Several people interested in the topic sought me out at the conference, introduced themselves, and we have subsequently stayed in touch.”

The manuscript published in JHM has been cited four times, including in a position paper from SHM and the Society of Critical Care Medicine.³ Another outgrowth of the research was being asked to contribute a chapter on hospitalists’ role in the ICU to a textbook on hospital medicine. Based on her still-fresh HM presentation, Dr. Wise was one of the few publicly identified experts on the subject. The chapter, co-authored by fellow Emory hospitalist Michael Heisler, MD, MPH, “The Role of the Hospitalist in Critical Care” was included in Principles and Practices of Hospital Medicine.⁴

Shetal Shah, MD, FAAP

Title: Neonatal intensivist

Institution: Stony Brook University Hospital, Great Neck, N.Y.

Year: 2006

RIV: “Administration of Inactivated Trivalent Influenza Vaccine (TIV) to Parents of Infants in the Neonatal Intensive Care Unit (NICU): A Novel Strategy to Increase Vaccination Rates” (innovations)

Citation: Shah SI, Caprio M, Hendricks-Munoz K. Administration of inactivated trivalent influenza vaccine to parents of high-risk infants in the neonatal intensive care unit. Pediatrics. 2007;120;e617-e621.

Dr. Shah was in his final year of a fellowship in neonatology at New York University when he took on the challenge of improving immunization access to protect premature, highly vulnerable patients in the NICU from influenza infections. Because these children are too young to be vaccinated directly, the concept of cocooning them from infection involves extending protection to everyone around them.

“We came up with the idea of offering flu vaccinations 24/7 in the NICU to the children’s parents,” he says. “It worked well for us as a way to define an indicated therapy for a defined population, even if it was a little outside the box. By the end of the flu season, 95% of the parents were vaccinated.”

SHM recognized the project as the top RIV innovations poster at HM06, but that was just the beginning.

“When I moved to SUNY Stony Brook, I continued to study and advocate for these vaccinations,” Dr. Shah says. “We were giving 500 to 700 vaccinations a year. Then I wrote a national resolution for the American Academy of Pediatrics, which was significant because it meant AAP was behind the project.”

Dr. Shah later became chair of AAP’s Long Island Chapter Legislative Committee and joined a statewide pediatric advocacy group. In 2009, the New York legislature enacted the Neonatal Influenza Protection Act, which required hospitals in the state to offer parents the vaccine, with Dr. Shah’s research and advocacy providing an essential basis for its passage. He’s even been recognized for his research in congressional citations.

Based on that success with influenza vaccinations, Dr. Shah and his colleagues looked at other diseases, starting with pertussis, and then tetanus, diphtheria, and whooping cough.⁵ All the while, they continued tracking immunization rates. A second state law, passed in 2011, added pertussis to the vaccinations. Next on his advocacy agenda is a project to promote smoking-cessation interventions in the NICU.⁶

“These parents come to see us every day,” he says. “What can we do, through the parents, to promote the health and well-being of their high-risk newborns?”

Jason Morrow, MD, PhD

Title: Assistant professor of medicine; medical director of inpatient palliative-care consultation

Institution: University of Texas Health Sciences Center, San Antonio

Year: 2009

RIV: “When to Depend on the Kinins of Strangers: An Unusual Case of Abdominal Pain” (clinical vignettes)

Publication: An article on the ethics of determining code status for patients with advanced cancer and a book chapter on the “last hours of life” for a forthcoming book on palliative care and hospital medicine.

As a medical resident, Dr. Morrow met a 27-year-old woman who had chronic abdominal pain and had made multiple visits to the ED for this complaint. The patient had a history of substance abuse and requested dilaudid for her pain—making it easy for staff to consign her to the stereotype of the difficult patient.

“I met her after an interesting finding,” he says. “It turns out that on the previous emergency room visit, she received a CAT scan, which showed duodenal and small-bowel thickening consistent with hereditary angioedema, although with an unusual presentation. As it happened, we had onsite a world expert in angioedema.”

The expert was able to confirm the diagnosis, Dr. Morrow says.

“By giving her this ‘legitimate,’ organic diagnosis, it just changed the whole dynamic of her relationship with her doctors,” he says. “She knew that they knew something was really wrong. The residents were empowered to have something to hang their hats on. And we were able to get better control of her pain.”

Dr. Morrow says he came on the scene late in the discovery process, but he helped to solve the puzzle, and then put together the abstract and poster that told the story of making the diagnosis.

“In my previous job, I was hired as a hospitalist but helped to build the palliative-care program within the hospital-medicine service,” he says. “In my current job, I was brought in to build the inpatient palliative-care-consultation service, although I still moonlight as a hospitalist to stay sharp.”

Dr. Morrow says he enjoys sharing stories of difficult cases and submitting case studies about them to medical conferences, often with clever titles incorporating puns (e.g. the 2009 SHM poster citing kinins, polypeptides in the blood that cause inflammation). Another example is “The Angina Monologues,” a story of an 82-year-old patient with chronic angina pectoris and complex pain syndromes that were difficult to bring under control. Palliative care also emphasizes patients’ stories, he says, in order to understand the person behind the diagnosis.

Larry Beresford is a freelance writer in San Francisco. References available at www.the-hospitalist.org.

References

Back to the Furture Past RIV winners talk about what the recognition meant for their careers By Larry Beresford

Twylla Tassava, MD

After winning SHM’s annual Research, Innovations, and Clinical Vignettes (RIV) scientific abstract and poster competition for an abstract illustrating a program that promoted flu vaccinations for families of neonatal patients, Shetal Shah, MD, FAAP, became a leading advocate for two laws mandating that New York hospitals offer vaccinations to families.

A poster that described a VTE prevention program led Gregory Maynard, MD, MSc, SFHM, to join SHM’s VTE Prevention Collaborative and, eventually, to become senior vice president of the society’s Center for Hospital Innovation and Improvement.

A prize-winning innovations poster for improving team communication by Vineet Chopra, MD, MS, FACP, FHM, and colleagues later took off as a new technology company.

Leonard Feldman, MD, FAAP, SFHM, won for a poster that explained online CME curriculum for hospitalists as consultants; the curriculum now resides on SHM’s website.

The evidence is clear: RIV abstracts are a vital part of hospital medicine.

Nearly 800 abstracts were submitted for HM13.

Awards are given in three categories:

• Research posters report clinical or basic science data, systematically review a clinical problem, or address efficiency, cost, or method of health-care delivery or medical decision-making;
• Innovations posters describe an existing innovative program in hospital medicine, often with preliminary data; and
• Clinical vignettes, either adult or pediatric, report on one or more cases illustrating a new disease entity, a prominent or unusual feature of an established disease, or an area of clinical controversy.

The Hospitalist asked 11 past RIV winners what the poster contest meant to their careers. Some added more data and analysis and went on to be published in such medical journals as the Journal of Hospital Medicine. Some used the recognition to launch or boost research-oriented careers; others saw their careers go in different directions.

“Winning a national poster competition gives you the confidence to continue to pursue your interest and take it to a higher level, like successfully competing for funding and publishing your line of inquiry,” says hospitalist and researcher Vineet Arora, MD, MPP, FHM, of the University of Chicago, who won the 2006 RIV research competition. “Sometimes, presenting posters can be lonely, but at SHM, you get a lot of traffic. You get a chance to practice your spiel, communicating science and research in a very concise way, which is an important skill to have.”

David Metzger, MD, PhD, also from the University of Chicago, who won the RIV research award in 2005, says recognition is a big deal, but “one of the biggest values of the RIV competition is just getting information out to colleagues, with the opportunity to talk with your peers. That’s the real prize.

“I’ve been involved in presenting posters at SHM every year that the society has been in existence,” he says. “I’ve met so many people and talked about what they’re doing. That’s what a medical society should do—bring people together like this.”

Twylla Tassava, MD

Title: Administrator, academic consult service; teaching staff physician

Institution: Saint Joseph Mercy Hospital, Ypsilanti, Mich.

Year: 2008

RIV: “A Case of Salty Voluminous Urine” (clinical vignette)

Dr. Tassava was honored two years in a row for topics drawn from her experience as a hospitalist working in the surgical ICU. Her HM08 entry won top poster, and her HM09 poster, “Permissive Hypernatremia: Co-Management of Intracranial Pressure in a Patient with Diabetes Insipidus,” was selected for an oral presentation.

The HM09 vignette described how the hypernatremia that occurs with diabetes insipidus could be used in a novel way to control intracranial pressure in a 17-year-old patient who had a traumatic brain injury from an auto accident.

“She had a beautiful outcome,” Dr. Tassava says. “She started college and she came back to our unit for a visit after her recovery.”

Dr. Tassava enjoyed the opportunity to explain to her peers how diabetes insipidus presented and how she managed the case. “I was a little surprised at how much discussion was generated by my case,” she says, “even though I knew this was an important and novel approach.”

When her hospital added intensivists, her work and research in the ICU ended and her career moved more toward hospitalist administration. She now runs the academic consult service at St. Joseph, serves as lead physician for the orthopedic surgery floor, instructs and mentors medical residents, and chairs the hospital’s Coagulation Collaborative Practice Team (Coagulation CPT). She credits the RIV honors with helping her to gain recognition as an academic hospitalist who was nominated for leadership roles. She has moved out of research for now but plans to pursue anticoagulation research in the future.

“I really appreciated the recognition for my curiosity and scientific approach, which was acknowledged by my surgical colleagues,” Dr. Tassava says. “I absolutely love the CPT. I am the hospital’s principal educator with regard to anticoagulation. Over the past year, I have given medicine and cardiology grand rounds, and have presented on the newest anticoagulants.”

Dr. Tassava still collaborates with her residents on abstracts, several of which have been submitted to SHM, the American College of Physicians, and other medical societies.

“I still love research,” she says. “I have a million ideas.”

Gregory Maynard, MD, MSc, SFHM

Title: Chief of the division of hospital medicine; senior vice president, SHM’s Center for Innovation and Improvement

Institution: University of California at San Diego (UCSD)

Year: 2008

RIV: “Prevention of Hospital-Acquired Venous Thromboembolism: Prospective Validation of a VTE Risk Assessment Model and Protocol” (research)

Citations: Maynard G, Stein J. Designing and implementing effective VTE prevention protocols: lessons from collaboratives. J Thromb Thrombolysis. 2010;29(2):159-166. Maynard G, Morris T, Jenkins I, et al. Optimizing prevention of hospital acquired venous thromboembolism: prospective validation of a VTE risk assessment model. J Hosp Med. 2010;5(1):10-18.

Dr. Maynard’s abstract described a project funded by the federal Agency for Healthcare Research and Quality to design and implement an organized, comprehensive protocol for VTE prevention within the hospital setting. The project also included a toolkit to help other hospitals do the same thing. The same group received SHM’s Award of Excellence for Teamwork.

This work, combined with similar efforts by Jason Stein, MD, and colleagues at Emory University in Atlanta and others, provided the foundation for SHM’s VTE resource room and the mentored implementation program of SHM’s VTE Prevention Collaborative, which had been launched in 2007 as one of the society’s first large-scale quality-improvement (QI) initiatives.

“SHM wanted to do something about VTE prevention, and when we got our AHRQ grant, I was interested in doing the same,” Dr. Maynard says. “We published our implementation guides on the AHRQ and SHM websites, along with a lot of valuable supporting materials.”

Dr. Maynard later took on leadership roles with SHM’s quality initiatives on glycemic control and care transitions, which made him the logical choice to become senior vice president of SHM’s Center for Hospital Innovation and Improvement.

He says the RIV honor lifted his profile not only within SHM, but also throughout the field, and it was instrumental in obtaining continued funding to advance the VTE initiative. “We did this tremendous work—with great results,” he says. “But I don’t think our local administrators appreciated it quite as much until we started to get external, national recognition.”

Dr. Maynard earned his master’s degree in biostatistics and clinical research design from the University of Michigan—skills he later brought to the academic setting at UCSD.

“It was a nice way for a hospitalist, who’s really a medical generalist, to become an expert in something,” he says. “I could never be more of an expert in cardiology than a cardiologist, or more of an expert in DVT than a hematologist or critical-care specialist. But I could help both of them do what they couldn’t do as effectively, which was to implement protocols reliably using a QI framework.”

Eduard E. Vasilevskis, MD

Title: Assistant professor of general internal medicine, hospital medicine, and public health

Institution: Vanderbilt University, Nashville, Tenn.

Year: 2009

RIV: “Predictors of Early Post-Discharge Mortality in Critically Ill Patients: Lessons for Quality Performance and Quality Assessment” (research)

Citation: Vasilevskis EE, Kuzniewicz MW, Cason BA, et al. Predictors of early post-discharge mortality in critically ill patients: a retrospective cohort study from the California Intensive Care Outcomes project. J Crit Care. 2011;26(1):65-75.

Dr. Vasilevskis has submitted abstracts to the RIV competition almost every year since 2007, when he was completing a fellowship at the University of California at San Francisco’s Institute for Health Policy Studies. He was honored in 2009 for a project based on the California Intensive Care Outcomes Project, which drew data from 35 hospitals to demonstrate that shortening ICU length of stay was predictive of early post-discharge mortality in the most severely ill patients.

He has continued to research quality and safety in the ICU, and he has published dozens of journal articles.

“My initial focus was on traditional mortality and length-of-stay outcomes,” he says. “I am now pursuing additional outcomes, most notably delirium in the ICU patient. I work with an amazing group of researchers that are trying to better measure, define, and treat delirium in the ICU—an outcome associated with a number of poor patient outcomes.”

Dr. Vasilevskis also is researching the causes of hospital readmissions and the development of novel ways to improve care transitions for elderly patients. He is pursuing a master’s of public health at Vanderbilt, and is co-principal investigator of an investigation of the Hospital Medicine Reengineering Network to improve transitions of care, supported by the Association of American Medical Colleges.

In addition to his 2009 win, he captured the HM10 and HM12 research categories. His HM12 poster, “Veterans Administration Acute Care 30-Day Mortality Model: Development, Validation and Performance Variation,” was singled out by the judging committee for its impressive sample size (1,114,327 patients in a retrospective cohort study of 131 VA hospitals), as well as for how it combined administrative and clinical risk models.

Dr. Vasilevskis says the opportunity to present his research at SHM and the recognition he received encouraged him to continue as a hospitalist engaged in medical research. He has been a member of SHM’s Research Committee since 2009, an RIV judge at HM11, and chaired the HM13 RIV competition subcommittee.

Vineet Chopra, MD, MS, FACP, FHM

Title: Assistant professor of medicine

Institution: University of Michigan Health System, Ann Arbor

Year: 2009

RIV: “MComm: Redefining Medical Communications in the 21st Century” (innovations)

Early in his career, Dr. Chopra was curious about how to improve the way patient care is delivered in the hospital setting. He was particularly interested in the inordinate amount of time hospitalists spend every day on communication.

“I saw one-way paging systems as a problem for communication between members of the medical team,” he says. “Doctors get paged and break off from what they’re doing to return the page—to someone who often isn’t there to take the call back. Sometimes the system gives us the wrong number or a cryptic message that makes no sense.”

A technological solution to this problem, which he and hospitalist Prasanth Gogineni, MD, conceived, designed, and created, then tested at the University of Michigan, is called MComm. Dr. Chopra describes it as a novel, uniform way of messaging for the entire medical team using wireless servers, PUSH technology, and iPhones. MComm was built around existing hospital workflow and patient-specific task lists, assigning priority to each message and documenting that it was delivered. The junior faculty members submitted an abstract about their innovative application, not really expecting it to get accepted. But when it won the poster competition and was selected for a plenary presentation, things got busy in a hurry. Specifically, the university hospital’s Office of Technology Transfer took a keen interest.

“We met with a number of people who had business experience in the health-care-technology space and found a CEO for the company we formed to develop MComm,” Dr. Chopra says. “I found myself getting pulled into it very quickly, with a lot of conversations about commercialization, revenue-sharing models, intellectual property, and the like.”

But running a company was not something Dr. Chopra wanted to do. Two years ago, that company, Synaptin, went one way and he went another—he stayed at Michigan as a medical researcher. He remains deeply interested in how care is delivered to hospitalized patients, but with a focus on such patient-safety questions as how to prevent negative outcomes from indwelling venous catheters.

“Winning the poster competition opened doors for me—there’s no doubt in my mind,” he says. “We demonstrated the ability to deliver a project of significance, from concept to prototype, without formal training in this area. If we didn’t have that recognition, I’m not sure I would have been ready to step into a research career as quickly. It helped me realize that medical research was what I wanted to do.”

Vineet Arora, MD, MPP, FHM

Title: Associate program director, internal-medicine residency; assistant dean of scholarship and discovery

Institution: Pritzker School of Medicine, University of Chicago

Year: 2006

RIV: “Measuring Quality of Hospital Care for Vulnerable Elders: Use of ACOVE Quality Indicators” (research)

Citation: Arora VM, Fish M, Basu A, et al. Relationship between quality of care of hospitalized vulnerable elders and postdischarge mortality. J Am Geriatrics. 2010;58:1642-1648.

David O. Meltzer, MD, PhD

Title: Associate professor, department of medicine; associate faculty member, Harris School and the Department of Economics

Institution: University of Chicago

Year: 2005

RIV: “Effects of Hospitalists on Outcomes and Costs in a Multicenter Trial of Academic Hospitalists” (research)

Dr. Meltzer was the lead author, with 11 other prominent hospitalists, of an abstract based on a multisite study of the cost and outcome implications of the hospitalist model—still a relatively new concept in 2001, when the research began. Although the study did not uncover large cost savings realized from the hospitalist model of care, as some advocates had hoped, important findings and implications for the emerging field were teased out of the data.

At the time, only a few randomly controlled, multisite studies of costs and outcomes for the hospitalist model had been performed. The study, Dr. Meltzer says, required a complicated analysis to discover that hospitalists, in fact, saved their facilities money, with their most important impact realized post-hospitalization, such as on nursing-home costs. It was important to control for spillover effect and the fact that hospitalists do a better job of teaching house staff, while a physician’s years of experience was another important variable, he says.

Dr. Meltzer was a medical researcher interested in medical specialization when the term “hospitalist” was first coined in 1996. “I thought, here was a chance to study a medical specialty in its formative stages,” he says.

He still works as a hospitalist, although with limited clinical time. In addition to his administrative work as division chief, he directs the Center for Health and the Social Sciences at the University of Chicago. His research interests include cost-effectiveness, technology assessment, and information research.

In 2010, his poster “Effects of Hospitalists on 1-Year Post-Discharge Resource Utilization by Medicare Beneficiaries” took the top prize in the HM10 research competition. In 2011, he was appointed to the methodology committee of the federal Patient-Centered Outcomes Research Institute (PCORI), which was created by the Affordable Care Act to advise the government on clinical-effectiveness research. He also sits on the Advisory Council to the National Institute of General Medical Sciences at the Institute of Medicine, and on the Congressional Budget Office’s panel of health advisors.

In a career full of recognition, Dr. Meltzer says it’s hard to pinpoint the impact of winning the poster contest. But he has continued to submit abstracts to SHM every year and appreciates the opportunities for interaction with peers at the poster exhibits.

Paul J. Grant, MD, FACP, SFHM

Title: Director of perioperative and consultative medicine

Institution: University of Michigan, Ann Arbor

Year: 2006

RIV: “Disseminated Histoplasmosis Presenting As Painful Oral Ulcers” (clinical vignettes)

Dr. Grant’s winning vignette presented a patient with a complex medical history, including heart disease and four months of painful oral ulcers, for which prior evaluations had been inconclusive, despite conducting biopsies. Following administration of high-dose corticosteroids, the patient’s condition worsened on multiple fronts. The vignette showed how the medical team was able to diagnose an unusual presentation of a fungal infection called histoplasmosis, which is prevalent in parts of the Midwest surrounding the Ohio and Mississippi river valleys.

“We see a lot of cases in the hospital where there are different angles you could take to turn it into a clinical vignette or a nice poster with good teaching points,” Dr. Grant says. “In this case, just digging deeper into the actual diagnosis was important because the empiric use of steroids can be fatal for some patients. Steroids are given for a lot of good reasons, but in this patient they caused immune suppression, allowing a smoldering infection to become very active.”

Dr. Grant did not submit the vignette for publication. “That was probably a mistake on my part,” he says, acknowledging the common complaint of too little time and too many competing priorities. But his interest in research has continued.

“I became involved at a national level with issues of perioperative medicine and last August published a textbook on the subject,” he reports.¹ “VTE is another area of interest I have developed since my hospital medicine fellowship.”

He serves as the VTE resource expert on the Michigan Hospital Medicine Safety Consortium, a quality collaborative of more than 40 hospitals with Blue Cross/Blue Shield of Michigan. “It’s exciting to be able to look at the risk factors, what kinds of patients get VTEs, and whether they were appropriately prophylaxed in the hospital,” he says.

VTE is a national quality priority, and Dr. Grant expects abstracts to emerge from the consortium’s work.

He says he appreciates the opportunities that arise from participating in poster sessions at SHM, where medical students, residents, and working hospitalists talk to the presenters of interesting cases.

“It gives you a real back-and-forth, which is good for the person asking the question and for the presenter,” he says, noting hospitalists from other parts of the country were not as familiar with histoplasmosis.

He says winning the HM06 poster contest helped him “get his feet wet” and feel more prepared for a career in academic hospital medicine. “I’m sure the award solidified my employers’ satisfaction in hiring me—and in giving me more desirable academic roles and responsibilities,” he adds.

Leonard Feldman, MD, FACP, FAAP, SFHM

Title: Assistant professor of medicine pediatrics; director of the general internal-medicine comprehensive consultation service

Institution: Johns Hopkins Hospital, Baltimore

Year: 2009

RIV: “An Internet-Based Consult Curriculum for Hospitalists” (innovations)

Dr. Feldman’s poster described an online CME curriculum for hospitalists acting as medical consultants. The concept grew out of a perceived deficiency in his own medical education when, in 2004, he was asked to lead the consultation service at Johns Hopkins—just six months after finishing his residency.

“I had no idea what I was doing as a general-internal-medicine consultant,” he says. “I maybe received two weeks of experience as a consultant during my residency. I was willing to take it on, learning on the job and asking for help. But it occurred to me that I’m probably not alone in feeling unprepared.”

In his quest for self-education, Dr. Feldman wondered whether he should write a textbook on the subject. “But the information changes so quickly, I thought I’d have a better chance to reach people online,” he notes.

After talking to publishers and CME companies, he came up with the concept of learning modules on perioperative and consultative medicine topics, which could be taken online while earning CME credits. Johns Hopkins served as the CME certifier, and medical-education company Advanced Studies in Medicine joined as a partner. Once the project got off the ground, a medical advisory committee was convened.

“Winning the SHM poster competition is a great honor to have on a CV. It really helps to legitimize your name in the world of hospital medicine,” Dr. Feldman says. “It also provided confirmation that we were on the right track with the curriculum project. People valued what we were doing.”

Dr. Feldman and SHM have since become affiliated, and the “Consultative and Perioperative Medicine Essentials for Hospitalists” modules are available on SHM’s website (www.shmconsults.com). The site has 12,000 registered members completing 500 CME modules every month.

“I do a lot of the editing still,” Dr. Feldman says. “We update the modules every two years and are still creating new ones.”

Dr. Feldman also pursues a number of clinical-research interests, including resident education and costs of care.

Kristin Wise, MD, FHM

Title: Assistant professor of medicine

Institution: Medical University of South Carolina, Charleston

Year: 2009

RIV: “Intensivists versus Hospitalists in the ICU: A Prospective Cohort Study Comparing Mortality and Length of Stay Between Two Staffing Models” (research) Citation: Wise KR, Akopov VA, Williams BR, Ido MS, Leeper KV, Dressler DD. Hospitalists and intensivists in the medical ICU: a prospective and observational study comparing mortality and length of stay between two staffing models. J Hosp Med. 2012;7(3):183-189.

Dr. Wise was recognized for research that began while she worked at Emory University in Atlanta, comparing hospitalists and intensivists in such outcomes as length of stay and mortality rates for patients in the ICU. The study was one of the first statistically rigorous examinations of this critical quality question. With an eye toward improving patient safety, national quality advocates such as the Leapfrog Group have called for hospitals to employ intensivists (critical-care specialists) to manage the care of ICU patients. In reality, Dr. Wise says, there aren’t enough intensivists to meet the need.

“Hospitalists are in the ICU anyway,” she says. “We just don’t have enough data to answer how well they do [in comparison to intensivists].”

Through a prospective cohort study of more than 1,000 patients, Dr. Wise’s group found that there was essentially no statistical difference in mortality rates between patients treated by intensivist teams or hospitalist ICU teams.

“We were also able to look at some of the intermediate-acuity patients—fairly complicated but not requiring ventilators,” she explains. “Our study wasn’t sufficiently powered for this subgroup, but it was an interesting piece of data to raise the question: Where should we deploy this scarce resource of intensivists? Which pockets of patients?”

Presenting her abstract at SHM’s annual meeting was a “good experience.”

“I’d done public speaking before, but never with an audience of about 500 people,” she says. “To go out there and field their questions was a real professional growing experience. Several people interested in the topic sought me out at the conference, introduced themselves, and we have subsequently stayed in touch.”

The manuscript published in JHM has been cited four times, including in a position paper from SHM and the Society of Critical Care Medicine.³ Another outgrowth of the research was being asked to contribute a chapter on hospitalists’ role in the ICU to a textbook on hospital medicine. Based on her still-fresh HM presentation, Dr. Wise was one of the few publicly identified experts on the subject. The chapter, co-authored by fellow Emory hospitalist Michael Heisler, MD, MPH, “The Role of the Hospitalist in Critical Care” was included in Principles and Practices of Hospital Medicine.⁴

Shetal Shah, MD, FAAP

Title: Neonatal intensivist

Institution: Stony Brook University Hospital, Great Neck, N.Y.

Year: 2006

RIV: “Administration of Inactivated Trivalent Influenza Vaccine (TIV) to Parents of Infants in the Neonatal Intensive Care Unit (NICU): A Novel Strategy to Increase Vaccination Rates” (innovations)

Citation: Shah SI, Caprio M, Hendricks-Munoz K. Administration of inactivated trivalent influenza vaccine to parents of high-risk infants in the neonatal intensive care unit. Pediatrics. 2007;120;e617-e621.

Dr. Shah was in his final year of a fellowship in neonatology at New York University when he took on the challenge of improving immunization access to protect premature, highly vulnerable patients in the NICU from influenza infections. Because these children are too young to be vaccinated directly, the concept of cocooning them from infection involves extending protection to everyone around them.

“We came up with the idea of offering flu vaccinations 24/7 in the NICU to the children’s parents,” he says. “It worked well for us as a way to define an indicated therapy for a defined population, even if it was a little outside the box. By the end of the flu season, 95% of the parents were vaccinated.”

SHM recognized the project as the top RIV innovations poster at HM06, but that was just the beginning.

“When I moved to SUNY Stony Brook, I continued to study and advocate for these vaccinations,” Dr. Shah says. “We were giving 500 to 700 vaccinations a year. Then I wrote a national resolution for the American Academy of Pediatrics, which was significant because it meant AAP was behind the project.”

Dr. Shah later became chair of AAP’s Long Island Chapter Legislative Committee and joined a statewide pediatric advocacy group. In 2009, the New York legislature enacted the Neonatal Influenza Protection Act, which required hospitals in the state to offer parents the vaccine, with Dr. Shah’s research and advocacy providing an essential basis for its passage. He’s even been recognized for his research in congressional citations.

Based on that success with influenza vaccinations, Dr. Shah and his colleagues looked at other diseases, starting with pertussis, and then tetanus, diphtheria, and whooping cough.⁵ All the while, they continued tracking immunization rates. A second state law, passed in 2011, added pertussis to the vaccinations. Next on his advocacy agenda is a project to promote smoking-cessation interventions in the NICU.⁶

“These parents come to see us every day,” he says. “What can we do, through the parents, to promote the health and well-being of their high-risk newborns?”

Jason Morrow, MD, PhD

Title: Assistant professor of medicine; medical director of inpatient palliative-care consultation

Institution: University of Texas Health Sciences Center, San Antonio

Year: 2009

RIV: “When to Depend on the Kinins of Strangers: An Unusual Case of Abdominal Pain” (clinical vignettes)

Publication: An article on the ethics of determining code status for patients with advanced cancer and a book chapter on the “last hours of life” for a forthcoming book on palliative care and hospital medicine.

As a medical resident, Dr. Morrow met a 27-year-old woman who had chronic abdominal pain and had made multiple visits to the ED for this complaint. The patient had a history of substance abuse and requested dilaudid for her pain—making it easy for staff to consign her to the stereotype of the difficult patient.

“I met her after an interesting finding,” he says. “It turns out that on the previous emergency room visit, she received a CAT scan, which showed duodenal and small-bowel thickening consistent with hereditary angioedema, although with an unusual presentation. As it happened, we had onsite a world expert in angioedema.”

The expert was able to confirm the diagnosis, Dr. Morrow says.

“By giving her this ‘legitimate,’ organic diagnosis, it just changed the whole dynamic of her relationship with her doctors,” he says. “She knew that they knew something was really wrong. The residents were empowered to have something to hang their hats on. And we were able to get better control of her pain.”

Dr. Morrow says he came on the scene late in the discovery process, but he helped to solve the puzzle, and then put together the abstract and poster that told the story of making the diagnosis.

“In my previous job, I was hired as a hospitalist but helped to build the palliative-care program within the hospital-medicine service,” he says. “In my current job, I was brought in to build the inpatient palliative-care-consultation service, although I still moonlight as a hospitalist to stay sharp.”

Dr. Morrow says he enjoys sharing stories of difficult cases and submitting case studies about them to medical conferences, often with clever titles incorporating puns (e.g. the 2009 SHM poster citing kinins, polypeptides in the blood that cause inflammation). Another example is “The Angina Monologues,” a story of an 82-year-old patient with chronic angina pectoris and complex pain syndromes that were difficult to bring under control. Palliative care also emphasizes patients’ stories, he says, in order to understand the person behind the diagnosis.

Larry Beresford is a freelance writer in San Francisco. References available at www.the-hospitalist.org.

References

Back to the Furture Past RIV winners talk about what the recognition meant for their careers By Larry Beresford

Twylla Tassava, MD

After winning SHM’s annual Research, Innovations, and Clinical Vignettes (RIV) scientific abstract and poster competition for an abstract illustrating a program that promoted flu vaccinations for families of neonatal patients, Shetal Shah, MD, FAAP, became a leading advocate for two laws mandating that New York hospitals offer vaccinations to families.

A poster that described a VTE prevention program led Gregory Maynard, MD, MSc, SFHM, to join SHM’s VTE Prevention Collaborative and, eventually, to become senior vice president of the society’s Center for Hospital Innovation and Improvement.

A prize-winning innovations poster for improving team communication by Vineet Chopra, MD, MS, FACP, FHM, and colleagues later took off as a new technology company.

Leonard Feldman, MD, FAAP, SFHM, won for a poster that explained online CME curriculum for hospitalists as consultants; the curriculum now resides on SHM’s website.

The evidence is clear: RIV abstracts are a vital part of hospital medicine.

Nearly 800 abstracts were submitted for HM13.

Awards are given in three categories:

• Research posters report clinical or basic science data, systematically review a clinical problem, or address efficiency, cost, or method of health-care delivery or medical decision-making;
• Innovations posters describe an existing innovative program in hospital medicine, often with preliminary data; and
• Clinical vignettes, either adult or pediatric, report on one or more cases illustrating a new disease entity, a prominent or unusual feature of an established disease, or an area of clinical controversy.

The Hospitalist asked 11 past RIV winners what the poster contest meant to their careers. Some added more data and analysis and went on to be published in such medical journals as the Journal of Hospital Medicine. Some used the recognition to launch or boost research-oriented careers; others saw their careers go in different directions.

“Winning a national poster competition gives you the confidence to continue to pursue your interest and take it to a higher level, like successfully competing for funding and publishing your line of inquiry,” says hospitalist and researcher Vineet Arora, MD, MPP, FHM, of the University of Chicago, who won the 2006 RIV research competition. “Sometimes, presenting posters can be lonely, but at SHM, you get a lot of traffic. You get a chance to practice your spiel, communicating science and research in a very concise way, which is an important skill to have.”

David Metzger, MD, PhD, also from the University of Chicago, who won the RIV research award in 2005, says recognition is a big deal, but “one of the biggest values of the RIV competition is just getting information out to colleagues, with the opportunity to talk with your peers. That’s the real prize.

“I’ve been involved in presenting posters at SHM every year that the society has been in existence,” he says. “I’ve met so many people and talked about what they’re doing. That’s what a medical society should do—bring people together like this.”

Twylla Tassava, MD

Title: Administrator, academic consult service; teaching staff physician

Institution: Saint Joseph Mercy Hospital, Ypsilanti, Mich.

Year: 2008

RIV: “A Case of Salty Voluminous Urine” (clinical vignette)

Dr. Tassava was honored two years in a row for topics drawn from her experience as a hospitalist working in the surgical ICU. Her HM08 entry won top poster, and her HM09 poster, “Permissive Hypernatremia: Co-Management of Intracranial Pressure in a Patient with Diabetes Insipidus,” was selected for an oral presentation.

The HM09 vignette described how the hypernatremia that occurs with diabetes insipidus could be used in a novel way to control intracranial pressure in a 17-year-old patient who had a traumatic brain injury from an auto accident.

“She had a beautiful outcome,” Dr. Tassava says. “She started college and she came back to our unit for a visit after her recovery.”

Dr. Tassava enjoyed the opportunity to explain to her peers how diabetes insipidus presented and how she managed the case. “I was a little surprised at how much discussion was generated by my case,” she says, “even though I knew this was an important and novel approach.”

When her hospital added intensivists, her work and research in the ICU ended and her career moved more toward hospitalist administration. She now runs the academic consult service at St. Joseph, serves as lead physician for the orthopedic surgery floor, instructs and mentors medical residents, and chairs the hospital’s Coagulation Collaborative Practice Team (Coagulation CPT). She credits the RIV honors with helping her to gain recognition as an academic hospitalist who was nominated for leadership roles. She has moved out of research for now but plans to pursue anticoagulation research in the future.

“I really appreciated the recognition for my curiosity and scientific approach, which was acknowledged by my surgical colleagues,” Dr. Tassava says. “I absolutely love the CPT. I am the hospital’s principal educator with regard to anticoagulation. Over the past year, I have given medicine and cardiology grand rounds, and have presented on the newest anticoagulants.”

Dr. Tassava still collaborates with her residents on abstracts, several of which have been submitted to SHM, the American College of Physicians, and other medical societies.

“I still love research,” she says. “I have a million ideas.”

Gregory Maynard, MD, MSc, SFHM

Title: Chief of the division of hospital medicine; senior vice president, SHM’s Center for Innovation and Improvement

Institution: University of California at San Diego (UCSD)

Year: 2008

RIV: “Prevention of Hospital-Acquired Venous Thromboembolism: Prospective Validation of a VTE Risk Assessment Model and Protocol” (research)

Citations: Maynard G, Stein J. Designing and implementing effective VTE prevention protocols: lessons from collaboratives. J Thromb Thrombolysis. 2010;29(2):159-166. Maynard G, Morris T, Jenkins I, et al. Optimizing prevention of hospital acquired venous thromboembolism: prospective validation of a VTE risk assessment model. J Hosp Med. 2010;5(1):10-18.

Dr. Maynard’s abstract described a project funded by the federal Agency for Healthcare Research and Quality to design and implement an organized, comprehensive protocol for VTE prevention within the hospital setting. The project also included a toolkit to help other hospitals do the same thing. The same group received SHM’s Award of Excellence for Teamwork.

This work, combined with similar efforts by Jason Stein, MD, and colleagues at Emory University in Atlanta and others, provided the foundation for SHM’s VTE resource room and the mentored implementation program of SHM’s VTE Prevention Collaborative, which had been launched in 2007 as one of the society’s first large-scale quality-improvement (QI) initiatives.

“SHM wanted to do something about VTE prevention, and when we got our AHRQ grant, I was interested in doing the same,” Dr. Maynard says. “We published our implementation guides on the AHRQ and SHM websites, along with a lot of valuable supporting materials.”

Dr. Maynard later took on leadership roles with SHM’s quality initiatives on glycemic control and care transitions, which made him the logical choice to become senior vice president of SHM’s Center for Hospital Innovation and Improvement.

He says the RIV honor lifted his profile not only within SHM, but also throughout the field, and it was instrumental in obtaining continued funding to advance the VTE initiative. “We did this tremendous work—with great results,” he says. “But I don’t think our local administrators appreciated it quite as much until we started to get external, national recognition.”

Dr. Maynard earned his master’s degree in biostatistics and clinical research design from the University of Michigan—skills he later brought to the academic setting at UCSD.

“It was a nice way for a hospitalist, who’s really a medical generalist, to become an expert in something,” he says. “I could never be more of an expert in cardiology than a cardiologist, or more of an expert in DVT than a hematologist or critical-care specialist. But I could help both of them do what they couldn’t do as effectively, which was to implement protocols reliably using a QI framework.”

Eduard E. Vasilevskis, MD

Title: Assistant professor of general internal medicine, hospital medicine, and public health

Institution: Vanderbilt University, Nashville, Tenn.

Year: 2009

RIV: “Predictors of Early Post-Discharge Mortality in Critically Ill Patients: Lessons for Quality Performance and Quality Assessment” (research)

Citation: Vasilevskis EE, Kuzniewicz MW, Cason BA, et al. Predictors of early post-discharge mortality in critically ill patients: a retrospective cohort study from the California Intensive Care Outcomes project. J Crit Care. 2011;26(1):65-75.

Dr. Vasilevskis has submitted abstracts to the RIV competition almost every year since 2007, when he was completing a fellowship at the University of California at San Francisco’s Institute for Health Policy Studies. He was honored in 2009 for a project based on the California Intensive Care Outcomes Project, which drew data from 35 hospitals to demonstrate that shortening ICU length of stay was predictive of early post-discharge mortality in the most severely ill patients.

He has continued to research quality and safety in the ICU, and he has published dozens of journal articles.

“My initial focus was on traditional mortality and length-of-stay outcomes,” he says. “I am now pursuing additional outcomes, most notably delirium in the ICU patient. I work with an amazing group of researchers that are trying to better measure, define, and treat delirium in the ICU—an outcome associated with a number of poor patient outcomes.”

Dr. Vasilevskis also is researching the causes of hospital readmissions and the development of novel ways to improve care transitions for elderly patients. He is pursuing a master’s of public health at Vanderbilt, and is co-principal investigator of an investigation of the Hospital Medicine Reengineering Network to improve transitions of care, supported by the Association of American Medical Colleges.

In addition to his 2009 win, he captured the HM10 and HM12 research categories. His HM12 poster, “Veterans Administration Acute Care 30-Day Mortality Model: Development, Validation and Performance Variation,” was singled out by the judging committee for its impressive sample size (1,114,327 patients in a retrospective cohort study of 131 VA hospitals), as well as for how it combined administrative and clinical risk models.

Dr. Vasilevskis says the opportunity to present his research at SHM and the recognition he received encouraged him to continue as a hospitalist engaged in medical research. He has been a member of SHM’s Research Committee since 2009, an RIV judge at HM11, and chaired the HM13 RIV competition subcommittee.

Vineet Chopra, MD, MS, FACP, FHM

Title: Assistant professor of medicine

Institution: University of Michigan Health System, Ann Arbor

Year: 2009

RIV: “MComm: Redefining Medical Communications in the 21st Century” (innovations)

Early in his career, Dr. Chopra was curious about how to improve the way patient care is delivered in the hospital setting. He was particularly interested in the inordinate amount of time hospitalists spend every day on communication.

“I saw one-way paging systems as a problem for communication between members of the medical team,” he says. “Doctors get paged and break off from what they’re doing to return the page—to someone who often isn’t there to take the call back. Sometimes the system gives us the wrong number or a cryptic message that makes no sense.”

A technological solution to this problem, which he and hospitalist Prasanth Gogineni, MD, conceived, designed, and created, then tested at the University of Michigan, is called MComm. Dr. Chopra describes it as a novel, uniform way of messaging for the entire medical team using wireless servers, PUSH technology, and iPhones. MComm was built around existing hospital workflow and patient-specific task lists, assigning priority to each message and documenting that it was delivered. The junior faculty members submitted an abstract about their innovative application, not really expecting it to get accepted. But when it won the poster competition and was selected for a plenary presentation, things got busy in a hurry. Specifically, the university hospital’s Office of Technology Transfer took a keen interest.

“We met with a number of people who had business experience in the health-care-technology space and found a CEO for the company we formed to develop MComm,” Dr. Chopra says. “I found myself getting pulled into it very quickly, with a lot of conversations about commercialization, revenue-sharing models, intellectual property, and the like.”

But running a company was not something Dr. Chopra wanted to do. Two years ago, that company, Synaptin, went one way and he went another—he stayed at Michigan as a medical researcher. He remains deeply interested in how care is delivered to hospitalized patients, but with a focus on such patient-safety questions as how to prevent negative outcomes from indwelling venous catheters.

“Winning the poster competition opened doors for me—there’s no doubt in my mind,” he says. “We demonstrated the ability to deliver a project of significance, from concept to prototype, without formal training in this area. If we didn’t have that recognition, I’m not sure I would have been ready to step into a research career as quickly. It helped me realize that medical research was what I wanted to do.”

Vineet Arora, MD, MPP, FHM

Title: Associate program director, internal-medicine residency; assistant dean of scholarship and discovery

Institution: Pritzker School of Medicine, University of Chicago

Year: 2006

RIV: “Measuring Quality of Hospital Care for Vulnerable Elders: Use of ACOVE Quality Indicators” (research)

Citation: Arora VM, Fish M, Basu A, et al. Relationship between quality of care of hospitalized vulnerable elders and postdischarge mortality. J Am Geriatrics. 2010;58:1642-1648.

David O. Meltzer, MD, PhD

Title: Associate professor, department of medicine; associate faculty member, Harris School and the Department of Economics

Institution: University of Chicago

Year: 2005

RIV: “Effects of Hospitalists on Outcomes and Costs in a Multicenter Trial of Academic Hospitalists” (research)

Dr. Meltzer was the lead author, with 11 other prominent hospitalists, of an abstract based on a multisite study of the cost and outcome implications of the hospitalist model—still a relatively new concept in 2001, when the research began. Although the study did not uncover large cost savings realized from the hospitalist model of care, as some advocates had hoped, important findings and implications for the emerging field were teased out of the data.

At the time, only a few randomly controlled, multisite studies of costs and outcomes for the hospitalist model had been performed. The study, Dr. Meltzer says, required a complicated analysis to discover that hospitalists, in fact, saved their facilities money, with their most important impact realized post-hospitalization, such as on nursing-home costs. It was important to control for spillover effect and the fact that hospitalists do a better job of teaching house staff, while a physician’s years of experience was another important variable, he says.

Dr. Meltzer was a medical researcher interested in medical specialization when the term “hospitalist” was first coined in 1996. “I thought, here was a chance to study a medical specialty in its formative stages,” he says.

He still works as a hospitalist, although with limited clinical time. In addition to his administrative work as division chief, he directs the Center for Health and the Social Sciences at the University of Chicago. His research interests include cost-effectiveness, technology assessment, and information research.

In 2010, his poster “Effects of Hospitalists on 1-Year Post-Discharge Resource Utilization by Medicare Beneficiaries” took the top prize in the HM10 research competition. In 2011, he was appointed to the methodology committee of the federal Patient-Centered Outcomes Research Institute (PCORI), which was created by the Affordable Care Act to advise the government on clinical-effectiveness research. He also sits on the Advisory Council to the National Institute of General Medical Sciences at the Institute of Medicine, and on the Congressional Budget Office’s panel of health advisors.

In a career full of recognition, Dr. Meltzer says it’s hard to pinpoint the impact of winning the poster contest. But he has continued to submit abstracts to SHM every year and appreciates the opportunities for interaction with peers at the poster exhibits.

Paul J. Grant, MD, FACP, SFHM

Title: Director of perioperative and consultative medicine

Institution: University of Michigan, Ann Arbor

Year: 2006

RIV: “Disseminated Histoplasmosis Presenting As Painful Oral Ulcers” (clinical vignettes)

Dr. Grant’s winning vignette presented a patient with a complex medical history, including heart disease and four months of painful oral ulcers, for which prior evaluations had been inconclusive, despite conducting biopsies. Following administration of high-dose corticosteroids, the patient’s condition worsened on multiple fronts. The vignette showed how the medical team was able to diagnose an unusual presentation of a fungal infection called histoplasmosis, which is prevalent in parts of the Midwest surrounding the Ohio and Mississippi river valleys.

“We see a lot of cases in the hospital where there are different angles you could take to turn it into a clinical vignette or a nice poster with good teaching points,” Dr. Grant says. “In this case, just digging deeper into the actual diagnosis was important because the empiric use of steroids can be fatal for some patients. Steroids are given for a lot of good reasons, but in this patient they caused immune suppression, allowing a smoldering infection to become very active.”

Dr. Grant did not submit the vignette for publication. “That was probably a mistake on my part,” he says, acknowledging the common complaint of too little time and too many competing priorities. But his interest in research has continued.

“I became involved at a national level with issues of perioperative medicine and last August published a textbook on the subject,” he reports.¹ “VTE is another area of interest I have developed since my hospital medicine fellowship.”

He serves as the VTE resource expert on the Michigan Hospital Medicine Safety Consortium, a quality collaborative of more than 40 hospitals with Blue Cross/Blue Shield of Michigan. “It’s exciting to be able to look at the risk factors, what kinds of patients get VTEs, and whether they were appropriately prophylaxed in the hospital,” he says.

VTE is a national quality priority, and Dr. Grant expects abstracts to emerge from the consortium’s work.

He says he appreciates the opportunities that arise from participating in poster sessions at SHM, where medical students, residents, and working hospitalists talk to the presenters of interesting cases.

“It gives you a real back-and-forth, which is good for the person asking the question and for the presenter,” he says, noting hospitalists from other parts of the country were not as familiar with histoplasmosis.

He says winning the HM06 poster contest helped him “get his feet wet” and feel more prepared for a career in academic hospital medicine. “I’m sure the award solidified my employers’ satisfaction in hiring me—and in giving me more desirable academic roles and responsibilities,” he adds.

Leonard Feldman, MD, FACP, FAAP, SFHM

Title: Assistant professor of medicine pediatrics; director of the general internal-medicine comprehensive consultation service

Institution: Johns Hopkins Hospital, Baltimore

Year: 2009

RIV: “An Internet-Based Consult Curriculum for Hospitalists” (innovations)

Dr. Feldman’s poster described an online CME curriculum for hospitalists acting as medical consultants. The concept grew out of a perceived deficiency in his own medical education when, in 2004, he was asked to lead the consultation service at Johns Hopkins—just six months after finishing his residency.

“I had no idea what I was doing as a general-internal-medicine consultant,” he says. “I maybe received two weeks of experience as a consultant during my residency. I was willing to take it on, learning on the job and asking for help. But it occurred to me that I’m probably not alone in feeling unprepared.”

In his quest for self-education, Dr. Feldman wondered whether he should write a textbook on the subject. “But the information changes so quickly, I thought I’d have a better chance to reach people online,” he notes.

After talking to publishers and CME companies, he came up with the concept of learning modules on perioperative and consultative medicine topics, which could be taken online while earning CME credits. Johns Hopkins served as the CME certifier, and medical-education company Advanced Studies in Medicine joined as a partner. Once the project got off the ground, a medical advisory committee was convened.

“Winning the SHM poster competition is a great honor to have on a CV. It really helps to legitimize your name in the world of hospital medicine,” Dr. Feldman says. “It also provided confirmation that we were on the right track with the curriculum project. People valued what we were doing.”

Dr. Feldman and SHM have since become affiliated, and the “Consultative and Perioperative Medicine Essentials for Hospitalists” modules are available on SHM’s website (www.shmconsults.com). The site has 12,000 registered members completing 500 CME modules every month.

“I do a lot of the editing still,” Dr. Feldman says. “We update the modules every two years and are still creating new ones.”

Dr. Feldman also pursues a number of clinical-research interests, including resident education and costs of care.

Kristin Wise, MD, FHM

Title: Assistant professor of medicine

Institution: Medical University of South Carolina, Charleston

Year: 2009

RIV: “Intensivists versus Hospitalists in the ICU: A Prospective Cohort Study Comparing Mortality and Length of Stay Between Two Staffing Models” (research) Citation: Wise KR, Akopov VA, Williams BR, Ido MS, Leeper KV, Dressler DD. Hospitalists and intensivists in the medical ICU: a prospective and observational study comparing mortality and length of stay between two staffing models. J Hosp Med. 2012;7(3):183-189.

Dr. Wise was recognized for research that began while she worked at Emory University in Atlanta, comparing hospitalists and intensivists in such outcomes as length of stay and mortality rates for patients in the ICU. The study was one of the first statistically rigorous examinations of this critical quality question. With an eye toward improving patient safety, national quality advocates such as the Leapfrog Group have called for hospitals to employ intensivists (critical-care specialists) to manage the care of ICU patients. In reality, Dr. Wise says, there aren’t enough intensivists to meet the need.

“Hospitalists are in the ICU anyway,” she says. “We just don’t have enough data to answer how well they do [in comparison to intensivists].”

Through a prospective cohort study of more than 1,000 patients, Dr. Wise’s group found that there was essentially no statistical difference in mortality rates between patients treated by intensivist teams or hospitalist ICU teams.

“We were also able to look at some of the intermediate-acuity patients—fairly complicated but not requiring ventilators,” she explains. “Our study wasn’t sufficiently powered for this subgroup, but it was an interesting piece of data to raise the question: Where should we deploy this scarce resource of intensivists? Which pockets of patients?”

Presenting her abstract at SHM’s annual meeting was a “good experience.”

“I’d done public speaking before, but never with an audience of about 500 people,” she says. “To go out there and field their questions was a real professional growing experience. Several people interested in the topic sought me out at the conference, introduced themselves, and we have subsequently stayed in touch.”

The manuscript published in JHM has been cited four times, including in a position paper from SHM and the Society of Critical Care Medicine.³ Another outgrowth of the research was being asked to contribute a chapter on hospitalists’ role in the ICU to a textbook on hospital medicine. Based on her still-fresh HM presentation, Dr. Wise was one of the few publicly identified experts on the subject. The chapter, co-authored by fellow Emory hospitalist Michael Heisler, MD, MPH, “The Role of the Hospitalist in Critical Care” was included in Principles and Practices of Hospital Medicine.⁴

Shetal Shah, MD, FAAP

Title: Neonatal intensivist

Institution: Stony Brook University Hospital, Great Neck, N.Y.

Year: 2006

RIV: “Administration of Inactivated Trivalent Influenza Vaccine (TIV) to Parents of Infants in the Neonatal Intensive Care Unit (NICU): A Novel Strategy to Increase Vaccination Rates” (innovations)

Citation: Shah SI, Caprio M, Hendricks-Munoz K. Administration of inactivated trivalent influenza vaccine to parents of high-risk infants in the neonatal intensive care unit. Pediatrics. 2007;120;e617-e621.

Dr. Shah was in his final year of a fellowship in neonatology at New York University when he took on the challenge of improving immunization access to protect premature, highly vulnerable patients in the NICU from influenza infections. Because these children are too young to be vaccinated directly, the concept of cocooning them from infection involves extending protection to everyone around them.

“We came up with the idea of offering flu vaccinations 24/7 in the NICU to the children’s parents,” he says. “It worked well for us as a way to define an indicated therapy for a defined population, even if it was a little outside the box. By the end of the flu season, 95% of the parents were vaccinated.”

SHM recognized the project as the top RIV innovations poster at HM06, but that was just the beginning.

“When I moved to SUNY Stony Brook, I continued to study and advocate for these vaccinations,” Dr. Shah says. “We were giving 500 to 700 vaccinations a year. Then I wrote a national resolution for the American Academy of Pediatrics, which was significant because it meant AAP was behind the project.”

Dr. Shah later became chair of AAP’s Long Island Chapter Legislative Committee and joined a statewide pediatric advocacy group. In 2009, the New York legislature enacted the Neonatal Influenza Protection Act, which required hospitals in the state to offer parents the vaccine, with Dr. Shah’s research and advocacy providing an essential basis for its passage. He’s even been recognized for his research in congressional citations.

Based on that success with influenza vaccinations, Dr. Shah and his colleagues looked at other diseases, starting with pertussis, and then tetanus, diphtheria, and whooping cough.⁵ All the while, they continued tracking immunization rates. A second state law, passed in 2011, added pertussis to the vaccinations. Next on his advocacy agenda is a project to promote smoking-cessation interventions in the NICU.⁶

“These parents come to see us every day,” he says. “What can we do, through the parents, to promote the health and well-being of their high-risk newborns?”

Jason Morrow, MD, PhD

Title: Assistant professor of medicine; medical director of inpatient palliative-care consultation

Institution: University of Texas Health Sciences Center, San Antonio

Year: 2009

RIV: “When to Depend on the Kinins of Strangers: An Unusual Case of Abdominal Pain” (clinical vignettes)

Publication: An article on the ethics of determining code status for patients with advanced cancer and a book chapter on the “last hours of life” for a forthcoming book on palliative care and hospital medicine.

As a medical resident, Dr. Morrow met a 27-year-old woman who had chronic abdominal pain and had made multiple visits to the ED for this complaint. The patient had a history of substance abuse and requested dilaudid for her pain—making it easy for staff to consign her to the stereotype of the difficult patient.

“I met her after an interesting finding,” he says. “It turns out that on the previous emergency room visit, she received a CAT scan, which showed duodenal and small-bowel thickening consistent with hereditary angioedema, although with an unusual presentation. As it happened, we had onsite a world expert in angioedema.”

The expert was able to confirm the diagnosis, Dr. Morrow says.

“By giving her this ‘legitimate,’ organic diagnosis, it just changed the whole dynamic of her relationship with her doctors,” he says. “She knew that they knew something was really wrong. The residents were empowered to have something to hang their hats on. And we were able to get better control of her pain.”

Dr. Morrow says he came on the scene late in the discovery process, but he helped to solve the puzzle, and then put together the abstract and poster that told the story of making the diagnosis.

“In my previous job, I was hired as a hospitalist but helped to build the palliative-care program within the hospital-medicine service,” he says. “In my current job, I was brought in to build the inpatient palliative-care-consultation service, although I still moonlight as a hospitalist to stay sharp.”

Dr. Morrow says he enjoys sharing stories of difficult cases and submitting case studies about them to medical conferences, often with clever titles incorporating puns (e.g. the 2009 SHM poster citing kinins, polypeptides in the blood that cause inflammation). Another example is “The Angina Monologues,” a story of an 82-year-old patient with chronic angina pectoris and complex pain syndromes that were difficult to bring under control. Palliative care also emphasizes patients’ stories, he says, in order to understand the person behind the diagnosis.

Larry Beresford is a freelance writer in San Francisco. References available at www.the-hospitalist.org.

References

click for large version

A shift in governmental regulations regarding reimbursement for hospital-acquired infections (HAIs) is forcing hospitals to take a closer look at how to reduce them. A recent study in Infection Control and Hospital Epidemiology shows that copper-alloy surfaces may be one such solution.³ According to the study, although only 9% of the touch surfaces in each ICU were replaced with copper components, there were 58% fewer HAI cases.¹

“Before these regulations, hospitals didn’t necessarily want technology to decrease HAI rates, because the more infections and complications, the longer the length of patient stay, the greater the reimbursement, and the better the bottom line,” says Archelle Georgiou, MD, president of Georgiou Consulting LLC in Minneapolis and an advisor to the Copper Development Association.

Three regulations that have resulted in reimbursements to hospitals getting cut include:

1. The Deficit Reduction Act of 2005, which was implemented on Oct. 1, 2008, which states that Medicare will not reimburse for certain types of HAIs;
2. Section 3025 of the Affordable Care Act (signed into law in 2010), which incentivizes hospitals to decrease their readmission rates, which frequently are caused by HAIs. Beginning this fall, hospitals are getting reduced reimbursement when their readmission rates exceed a certain threshold. The maximum penalty in 2013 is 1% and will increase to 3% by 2015; and
3. Section 1886 of the Affordable Care Act, which describes value-based purchasing and makes hospitals eligible to receive incentive payments for achieving better care on certain quality metrics. Funding for the program comes from withholding payment from poor-performing hospitals. The financial impact to hospitals started this year. In 2014, urinary tract infections and vascular-catheter-associated infections will be among the targeted conditions measured by CMS to calculate incentives and penalties.

“Hospitals are now feeling a direct impact from all of this,” Dr. Georgiou says. “Back in 2008, hospitals were noticing, but it was hard to get their attention since only one program was impacting their bottom line. But, pretty soon, hospitals risk losing upwards of 5% of their Medicare reimbursement for decreased quality.

“Reducing HAIs is clearly on the priority list of chief operating officers. They are very aware of the impact to their bottom line. They are looking to their vendors and suppliers to develop strategies to work with their hospitals to improve performance around these metrics.”

Karen Appold is a freelance writer in Pennsylvania.

click for large version

A shift in governmental regulations regarding reimbursement for hospital-acquired infections (HAIs) is forcing hospitals to take a closer look at how to reduce them. A recent study in Infection Control and Hospital Epidemiology shows that copper-alloy surfaces may be one such solution.³ According to the study, although only 9% of the touch surfaces in each ICU were replaced with copper components, there were 58% fewer HAI cases.¹

“Before these regulations, hospitals didn’t necessarily want technology to decrease HAI rates, because the more infections and complications, the longer the length of patient stay, the greater the reimbursement, and the better the bottom line,” says Archelle Georgiou, MD, president of Georgiou Consulting LLC in Minneapolis and an advisor to the Copper Development Association.

Three regulations that have resulted in reimbursements to hospitals getting cut include:

1. The Deficit Reduction Act of 2005, which was implemented on Oct. 1, 2008, which states that Medicare will not reimburse for certain types of HAIs;
2. Section 3025 of the Affordable Care Act (signed into law in 2010), which incentivizes hospitals to decrease their readmission rates, which frequently are caused by HAIs. Beginning this fall, hospitals are getting reduced reimbursement when their readmission rates exceed a certain threshold. The maximum penalty in 2013 is 1% and will increase to 3% by 2015; and
3. Section 1886 of the Affordable Care Act, which describes value-based purchasing and makes hospitals eligible to receive incentive payments for achieving better care on certain quality metrics. Funding for the program comes from withholding payment from poor-performing hospitals. The financial impact to hospitals started this year. In 2014, urinary tract infections and vascular-catheter-associated infections will be among the targeted conditions measured by CMS to calculate incentives and penalties.

“Hospitals are now feeling a direct impact from all of this,” Dr. Georgiou says. “Back in 2008, hospitals were noticing, but it was hard to get their attention since only one program was impacting their bottom line. But, pretty soon, hospitals risk losing upwards of 5% of their Medicare reimbursement for decreased quality.

“Reducing HAIs is clearly on the priority list of chief operating officers. They are very aware of the impact to their bottom line. They are looking to their vendors and suppliers to develop strategies to work with their hospitals to improve performance around these metrics.”

Karen Appold is a freelance writer in Pennsylvania.

click for large version

A shift in governmental regulations regarding reimbursement for hospital-acquired infections (HAIs) is forcing hospitals to take a closer look at how to reduce them. A recent study in Infection Control and Hospital Epidemiology shows that copper-alloy surfaces may be one such solution.³ According to the study, although only 9% of the touch surfaces in each ICU were replaced with copper components, there were 58% fewer HAI cases.¹

“Before these regulations, hospitals didn’t necessarily want technology to decrease HAI rates, because the more infections and complications, the longer the length of patient stay, the greater the reimbursement, and the better the bottom line,” says Archelle Georgiou, MD, president of Georgiou Consulting LLC in Minneapolis and an advisor to the Copper Development Association.

Three regulations that have resulted in reimbursements to hospitals getting cut include:

1. The Deficit Reduction Act of 2005, which was implemented on Oct. 1, 2008, which states that Medicare will not reimburse for certain types of HAIs;
2. Section 3025 of the Affordable Care Act (signed into law in 2010), which incentivizes hospitals to decrease their readmission rates, which frequently are caused by HAIs. Beginning this fall, hospitals are getting reduced reimbursement when their readmission rates exceed a certain threshold. The maximum penalty in 2013 is 1% and will increase to 3% by 2015; and
3. Section 1886 of the Affordable Care Act, which describes value-based purchasing and makes hospitals eligible to receive incentive payments for achieving better care on certain quality metrics. Funding for the program comes from withholding payment from poor-performing hospitals. The financial impact to hospitals started this year. In 2014, urinary tract infections and vascular-catheter-associated infections will be among the targeted conditions measured by CMS to calculate incentives and penalties.

“Hospitals are now feeling a direct impact from all of this,” Dr. Georgiou says. “Back in 2008, hospitals were noticing, but it was hard to get their attention since only one program was impacting their bottom line. But, pretty soon, hospitals risk losing upwards of 5% of their Medicare reimbursement for decreased quality.

“Reducing HAIs is clearly on the priority list of chief operating officers. They are very aware of the impact to their bottom line. They are looking to their vendors and suppliers to develop strategies to work with their hospitals to improve performance around these metrics.”

Karen Appold is a freelance writer in Pennsylvania.

Dr. Georgiou

It would be premature for a hospital to install copper based on this study if future studies confirm earlier results, then hospitals should seriously consider copper installations.

—James Pile, MD, FACP, SFHM, vice chair, department of hospital medicine, Cleveland Clinic

Hospital-acquired infections (HAIs) are on the rise despite efforts to decrease them. HAIs cause an estimated 100,000 deaths annually and account for up to $45 billion in health-care costs. Adding fuel to the fire, bacteria increasingly are becoming resistant to last-resort drugs. Despite this gloomy outlook, a recent study in Infection Control and Hospital Epidemiology shows that a material known for its antimicrobial properties for more than 4,000 years—copper—might be a light at the end of this darkening tunnel.¹

Ancient Indians stored water in copper pots to prevent illness, says lead study author Cassandra D. Salgado, MD, associate professor of medicine, hospital epidemiologist, and medical director for infection prevention at the Medical University of South Carolina (MUSC) in Charleston. But copper rarely is used in that manner today because molded plastics and stainless steel are less expensive and easier to mass-produce.

Dr. Salgado explains that the antimicrobial effect of copper-alloy surfaces is a result of the metal stealing electrons from the bacteria when they come into contact with each other. “Once the bacteria donate the electrons to the copper metal, this places the organism into a state of electrical-charge deficit,” she says. “As a consequence, free radicals are generated inside the cell, which ultimately leads to the cell’s death.”

Copper-alloy surfaces kill 99.9% of bacteria in less than two hours, says Harold T. Michels, PhD, PE, senior vice president of technology and technical services for Copper Development Association Inc. in New York, who was a study author. On other surfaces, bacteria may live for multiple days or even months.

Unlike current methods used to decrease HAIs (i.e. hand-washing and sanitizing surfaces), copper components don’t require human intervention or compliance to be effective.

“It supplements what these other things can do; it’s in the background and it’s always working,” Michels says.

A study needs to be done on the cost-effectiveness of copper surfaces. Health economists estimate that if copper surfaces were incorporated into ICUs, after three to six months, those surfaces would pay for themselves. That is not a long time period. Hospitals need to understand that there will be upfront costs but that they will realize benefits downstream.

—Cassandra D. Salgado, MD, associate professor of medicine, hospital epidemiologist, medical director for infection prevention, Medical University of South Carolina, Charleston

Study Specifics

To conduct the study, copper prototypes of items touched most frequently by patients, health-care providers, and visitors were made and placed in patient rooms located within ICUs. “We placed the copper around the patient [much like a defensive perimeter] to reduce the likelihood that the health-care worker or visitor would introduce the infectious agent to the patient,” says the study’s lead investigator, Michael Schmidt, PhD, a professor and vice chair of MUSC’s department of microbiology and immunology.

Then, bacterial loads were measured on each object. For every study room, there was a control room without copper objects. Researchers were most interested in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). For a period of time, bacterial burdens were measured in both copper rooms and control rooms.

Results exceeded the researchers’ expectations. Although only 7% of the touch surfaces in each ICU were replaced with copper components, there were 58% fewer HAI cases. The rate of HAI and/or MRSA or VRE colonization in ICU rooms with copper-alloy surfaces was significantly lower than that in standard ICU rooms (0.071 versus 0.123). For HAIs only, the rate was reduced to 0.034 from 0.081.³

“We were pleasantly surprised with the reductions,” Dr. Salgado says. “We consistently saw a more than 50% reduction in HAIs in all study sites.”

Archelle Georgiou, MD, president of Georgiou Consulting LLC in Minneapolis and an advisor to the Copper Development Association, is an advocate for making the health-care system simpler and safer for consumers. She says copper is a “game-changer.”

“It’s a brand-new way of thinking about decreasing the number of HAIs,” she says.

Green Light?

In light of the study’s encouraging findings, hospitalist and infectious-disease specialist James Pile, MD, FACP, SFHM, vice chair of the Department of Hospital Medicine at Cleveland Clinic, says that although study results appear valid, “it didn’t provide any final answers.”

Dr. Georgiou

“It would be premature for a hospital to install copper based on this study,” he says, adding he didn’t find the study results surprising, because copper is known to have antimicrobial properties.

But, Dr. Pile says, the study did provide proof of concept and opens the door for larger, more definitive studies that will show if installing copper in hospital rooms is worthwhile.

“If future studies confirm earlier results, then hospitals should seriously consider copper installations,” he says.

Dr. Georgiou

Barriers to Implementation

Despite the promising outlook for copper in dramatically reducing HAIs, implantation of copper components is off to a slow start.

Negotiations with the Environmental Protection Agency, the federal agency with jurisdiction over public-health claims for antimicrobial surfaces, started in 2004. Testing started in 2005. Although federal registration was completed in February 2008, it wasn’t until late 2011 that all regulatory issues were resolved for manufacturers.

“The regulatory process created delays in educating hospitals and the public about copper’s effectiveness in killing certain bacteria,” Dr. Georgiou explains. “As a result, American manufacturers with the ability to make copper components weren’t developing products because they couldn’t sell them.”

Now that the regulatory issues have been resolved, U.S. manufacturers are beginning to make copper components. The first wave of commercial products came on the market in late 2011. Meanwhile, European countries have not been delayed and are well ahead of U.S. hospitals in implementing copper components.

Presently, nine U.S. hospitals have installed some form of copper components, including door hardware, cabinet pulls, sinks, stretchers, and IV poles, Michels reports.

Despite these advances, hospitals may be slow to incorporate copper components due to a variety of reasons:

Cost. Dr. Pile believes that cost will be the major barrier. “Installing copper surfaces won’t be cheap,” he says. “But, then again, HAIs are very costly. I think it will be more difficult to justify their existence if they can be prevented. If copper is effective in preventing HAIs, it would prove to be cost-effective over time.”

Dr. Salgado concurs. “A study needs to be done on the cost-effectiveness of copper surfaces,” she says. “Health economists estimate that if copper surfaces were incorporated into ICUs, after three to six months, those surfaces would pay for themselves. That is not a long time period. Hospitals need to understand that there will be upfront costs but that they will realize benefits downstream.”

The Center for Medicare & Medicaid Services (CMS) has reported that one infection adds $43,000 in patient costs.⁴ A typical U.S. hospital room contains $100,000 worth of goods and equipment.

“When you do the math using the amount of copper in our study, the cost would be between $1 and $10 per patient,” Dr. Schmidt says. “It’s also important to note that an infection adds 19 days to a patient’s hospital stay.”

Aesthetics. For some, appearance may be a concern. “Copper is actually an appealing material that is offered in an array of colors and surface finishes,” Dr. Michels says. Because a copper-and-brass combination is more prone to tarnishing, a copper-nickel alloy may be more desirable.

Availability. Copper components are not produced and marketed to U.S. hospitals; however, they are available. “We are hoping with our study and future studies that some medical-device companies, as well as hospital-furniture manufacturers, will jump on board to look at ways to mass-produce items,” Dr. Salgado says.

Acceptance. The study published in Infection Control and Hospital Epidemiology validated the effectiveness of copper in decreasing HAIs. This pilot study, however, was not blinded.³

“It was pretty apparent to providers where copper surfaces were located, which tends to result in some bias. Future studies will, hopefully, try to answer questions regarding healthcare providers’ behaviors with different surfaces,” says Dr. Salgado, noting researchers in California and Chile also are studying the effects of copper surfaces in hospitals.

Possible loss of efficacy. Even if a surface is effective initially, Dr. Pile points out that it’s possible for that to change. “I have a theoretical concern that, over time, bacterial pathogens may develop a tolerance to copper,” he says. “Bacterial adversaries have been able to overcome any type of treatment that we have devised for them thus far. But this remains to be seen.”

This has been an issue with other surfaces; once microbes establish a foothold, it is hard to eliminate them. But Dr. Schmidt says because bacteria are killed so quickly on copper surfaces and cleaning is only required once daily, the ability to establish a foothold is greatly reduced, if not completely eliminated.

Copper supplements what these other things can do; it’s in the background and it’s always working..

—Harold T. Michels, PhD, PE, senior vice president of technology and technical services, Copper Development Association Inc.

Champion Proven Strategies

Dr. Pile sees antimicrobial stewardship as a great opportunity for hospitalists as a specialty. In fact, the Centers for Disease Control and Prevention is partnering with HM groups on piloting multiple antimicrobial stewardship initiatives at several sites.

Dr. Pile suggests that leaders spearhead formal quality-improvement efforts, be involved with patient-safety efforts, and serve as physician champions.

“No one is better positioned to do this than hospitalists, because we own the hospital environment,” he says. “We have an incredible stake in making sure that our inpatient environment provides safe and high-value care.”

As a result of the published study, Dr. Salgado says discussions are underway with hospital leaders at MUSC to determine if copper surfaces will be used in its ICUs and, if so, how changes will be implemented.

Karen Appold is a freelance writer in Pennsylvania.

References

1. Klevens RM, Edwards JR, Richards CL, et al. Estimating healthcare-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep. 2007;122:160-166.
2. Scott RD. The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of Prevention. Atlanta: Centers for Disease Control and Prevention, 2009.
3. Salgado CD, Sepkowitz KA, John JF, et al. Copper Surfaces Reduce the Rate of Healthcare-Acquired Infections in the Intensive Care Unit. Infect Control Hosp Epidemiol. 2013;34(5):479-486.
4. Healthcare Cost and Utilization Project. Statistical Brief No. 94. Agency for Healthcare Research and Quality. Aug. 2010. Available at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb94.pdf. Accessed Aug. 6, 2013.

Dr. Georgiou

It would be premature for a hospital to install copper based on this study if future studies confirm earlier results, then hospitals should seriously consider copper installations.

—James Pile, MD, FACP, SFHM, vice chair, department of hospital medicine, Cleveland Clinic

Hospital-acquired infections (HAIs) are on the rise despite efforts to decrease them. HAIs cause an estimated 100,000 deaths annually and account for up to $45 billion in health-care costs. Adding fuel to the fire, bacteria increasingly are becoming resistant to last-resort drugs. Despite this gloomy outlook, a recent study in Infection Control and Hospital Epidemiology shows that a material known for its antimicrobial properties for more than 4,000 years—copper—might be a light at the end of this darkening tunnel.¹

Ancient Indians stored water in copper pots to prevent illness, says lead study author Cassandra D. Salgado, MD, associate professor of medicine, hospital epidemiologist, and medical director for infection prevention at the Medical University of South Carolina (MUSC) in Charleston. But copper rarely is used in that manner today because molded plastics and stainless steel are less expensive and easier to mass-produce.

Dr. Salgado explains that the antimicrobial effect of copper-alloy surfaces is a result of the metal stealing electrons from the bacteria when they come into contact with each other. “Once the bacteria donate the electrons to the copper metal, this places the organism into a state of electrical-charge deficit,” she says. “As a consequence, free radicals are generated inside the cell, which ultimately leads to the cell’s death.”

Copper-alloy surfaces kill 99.9% of bacteria in less than two hours, says Harold T. Michels, PhD, PE, senior vice president of technology and technical services for Copper Development Association Inc. in New York, who was a study author. On other surfaces, bacteria may live for multiple days or even months.

Unlike current methods used to decrease HAIs (i.e. hand-washing and sanitizing surfaces), copper components don’t require human intervention or compliance to be effective.

“It supplements what these other things can do; it’s in the background and it’s always working,” Michels says.

A study needs to be done on the cost-effectiveness of copper surfaces. Health economists estimate that if copper surfaces were incorporated into ICUs, after three to six months, those surfaces would pay for themselves. That is not a long time period. Hospitals need to understand that there will be upfront costs but that they will realize benefits downstream.

—Cassandra D. Salgado, MD, associate professor of medicine, hospital epidemiologist, medical director for infection prevention, Medical University of South Carolina, Charleston

Study Specifics

To conduct the study, copper prototypes of items touched most frequently by patients, health-care providers, and visitors were made and placed in patient rooms located within ICUs. “We placed the copper around the patient [much like a defensive perimeter] to reduce the likelihood that the health-care worker or visitor would introduce the infectious agent to the patient,” says the study’s lead investigator, Michael Schmidt, PhD, a professor and vice chair of MUSC’s department of microbiology and immunology.

Then, bacterial loads were measured on each object. For every study room, there was a control room without copper objects. Researchers were most interested in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). For a period of time, bacterial burdens were measured in both copper rooms and control rooms.

Results exceeded the researchers’ expectations. Although only 7% of the touch surfaces in each ICU were replaced with copper components, there were 58% fewer HAI cases. The rate of HAI and/or MRSA or VRE colonization in ICU rooms with copper-alloy surfaces was significantly lower than that in standard ICU rooms (0.071 versus 0.123). For HAIs only, the rate was reduced to 0.034 from 0.081.³

“We were pleasantly surprised with the reductions,” Dr. Salgado says. “We consistently saw a more than 50% reduction in HAIs in all study sites.”

Archelle Georgiou, MD, president of Georgiou Consulting LLC in Minneapolis and an advisor to the Copper Development Association, is an advocate for making the health-care system simpler and safer for consumers. She says copper is a “game-changer.”

“It’s a brand-new way of thinking about decreasing the number of HAIs,” she says.

Green Light?

In light of the study’s encouraging findings, hospitalist and infectious-disease specialist James Pile, MD, FACP, SFHM, vice chair of the Department of Hospital Medicine at Cleveland Clinic, says that although study results appear valid, “it didn’t provide any final answers.”

Dr. Georgiou

“It would be premature for a hospital to install copper based on this study,” he says, adding he didn’t find the study results surprising, because copper is known to have antimicrobial properties.

But, Dr. Pile says, the study did provide proof of concept and opens the door for larger, more definitive studies that will show if installing copper in hospital rooms is worthwhile.

“If future studies confirm earlier results, then hospitals should seriously consider copper installations,” he says.

Dr. Georgiou

Barriers to Implementation

Despite the promising outlook for copper in dramatically reducing HAIs, implantation of copper components is off to a slow start.

Negotiations with the Environmental Protection Agency, the federal agency with jurisdiction over public-health claims for antimicrobial surfaces, started in 2004. Testing started in 2005. Although federal registration was completed in February 2008, it wasn’t until late 2011 that all regulatory issues were resolved for manufacturers.

“The regulatory process created delays in educating hospitals and the public about copper’s effectiveness in killing certain bacteria,” Dr. Georgiou explains. “As a result, American manufacturers with the ability to make copper components weren’t developing products because they couldn’t sell them.”

Now that the regulatory issues have been resolved, U.S. manufacturers are beginning to make copper components. The first wave of commercial products came on the market in late 2011. Meanwhile, European countries have not been delayed and are well ahead of U.S. hospitals in implementing copper components.

Presently, nine U.S. hospitals have installed some form of copper components, including door hardware, cabinet pulls, sinks, stretchers, and IV poles, Michels reports.

Despite these advances, hospitals may be slow to incorporate copper components due to a variety of reasons:

Cost. Dr. Pile believes that cost will be the major barrier. “Installing copper surfaces won’t be cheap,” he says. “But, then again, HAIs are very costly. I think it will be more difficult to justify their existence if they can be prevented. If copper is effective in preventing HAIs, it would prove to be cost-effective over time.”

Dr. Salgado concurs. “A study needs to be done on the cost-effectiveness of copper surfaces,” she says. “Health economists estimate that if copper surfaces were incorporated into ICUs, after three to six months, those surfaces would pay for themselves. That is not a long time period. Hospitals need to understand that there will be upfront costs but that they will realize benefits downstream.”

The Center for Medicare & Medicaid Services (CMS) has reported that one infection adds $43,000 in patient costs.⁴ A typical U.S. hospital room contains $100,000 worth of goods and equipment.

“When you do the math using the amount of copper in our study, the cost would be between $1 and $10 per patient,” Dr. Schmidt says. “It’s also important to note that an infection adds 19 days to a patient’s hospital stay.”

Aesthetics. For some, appearance may be a concern. “Copper is actually an appealing material that is offered in an array of colors and surface finishes,” Dr. Michels says. Because a copper-and-brass combination is more prone to tarnishing, a copper-nickel alloy may be more desirable.

Availability. Copper components are not produced and marketed to U.S. hospitals; however, they are available. “We are hoping with our study and future studies that some medical-device companies, as well as hospital-furniture manufacturers, will jump on board to look at ways to mass-produce items,” Dr. Salgado says.

Acceptance. The study published in Infection Control and Hospital Epidemiology validated the effectiveness of copper in decreasing HAIs. This pilot study, however, was not blinded.³

“It was pretty apparent to providers where copper surfaces were located, which tends to result in some bias. Future studies will, hopefully, try to answer questions regarding healthcare providers’ behaviors with different surfaces,” says Dr. Salgado, noting researchers in California and Chile also are studying the effects of copper surfaces in hospitals.

Possible loss of efficacy. Even if a surface is effective initially, Dr. Pile points out that it’s possible for that to change. “I have a theoretical concern that, over time, bacterial pathogens may develop a tolerance to copper,” he says. “Bacterial adversaries have been able to overcome any type of treatment that we have devised for them thus far. But this remains to be seen.”

This has been an issue with other surfaces; once microbes establish a foothold, it is hard to eliminate them. But Dr. Schmidt says because bacteria are killed so quickly on copper surfaces and cleaning is only required once daily, the ability to establish a foothold is greatly reduced, if not completely eliminated.

Copper supplements what these other things can do; it’s in the background and it’s always working..

—Harold T. Michels, PhD, PE, senior vice president of technology and technical services, Copper Development Association Inc.

Champion Proven Strategies

Dr. Pile sees antimicrobial stewardship as a great opportunity for hospitalists as a specialty. In fact, the Centers for Disease Control and Prevention is partnering with HM groups on piloting multiple antimicrobial stewardship initiatives at several sites.

Dr. Pile suggests that leaders spearhead formal quality-improvement efforts, be involved with patient-safety efforts, and serve as physician champions.

“No one is better positioned to do this than hospitalists, because we own the hospital environment,” he says. “We have an incredible stake in making sure that our inpatient environment provides safe and high-value care.”

As a result of the published study, Dr. Salgado says discussions are underway with hospital leaders at MUSC to determine if copper surfaces will be used in its ICUs and, if so, how changes will be implemented.

Karen Appold is a freelance writer in Pennsylvania.

References

1. Klevens RM, Edwards JR, Richards CL, et al. Estimating healthcare-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep. 2007;122:160-166.
2. Scott RD. The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of Prevention. Atlanta: Centers for Disease Control and Prevention, 2009.
3. Salgado CD, Sepkowitz KA, John JF, et al. Copper Surfaces Reduce the Rate of Healthcare-Acquired Infections in the Intensive Care Unit. Infect Control Hosp Epidemiol. 2013;34(5):479-486.
4. Healthcare Cost and Utilization Project. Statistical Brief No. 94. Agency for Healthcare Research and Quality. Aug. 2010. Available at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb94.pdf. Accessed Aug. 6, 2013.

Dr. Georgiou

It would be premature for a hospital to install copper based on this study if future studies confirm earlier results, then hospitals should seriously consider copper installations.

—James Pile, MD, FACP, SFHM, vice chair, department of hospital medicine, Cleveland Clinic

Hospital-acquired infections (HAIs) are on the rise despite efforts to decrease them. HAIs cause an estimated 100,000 deaths annually and account for up to $45 billion in health-care costs. Adding fuel to the fire, bacteria increasingly are becoming resistant to last-resort drugs. Despite this gloomy outlook, a recent study in Infection Control and Hospital Epidemiology shows that a material known for its antimicrobial properties for more than 4,000 years—copper—might be a light at the end of this darkening tunnel.¹

Ancient Indians stored water in copper pots to prevent illness, says lead study author Cassandra D. Salgado, MD, associate professor of medicine, hospital epidemiologist, and medical director for infection prevention at the Medical University of South Carolina (MUSC) in Charleston. But copper rarely is used in that manner today because molded plastics and stainless steel are less expensive and easier to mass-produce.

Dr. Salgado explains that the antimicrobial effect of copper-alloy surfaces is a result of the metal stealing electrons from the bacteria when they come into contact with each other. “Once the bacteria donate the electrons to the copper metal, this places the organism into a state of electrical-charge deficit,” she says. “As a consequence, free radicals are generated inside the cell, which ultimately leads to the cell’s death.”

Copper-alloy surfaces kill 99.9% of bacteria in less than two hours, says Harold T. Michels, PhD, PE, senior vice president of technology and technical services for Copper Development Association Inc. in New York, who was a study author. On other surfaces, bacteria may live for multiple days or even months.

Unlike current methods used to decrease HAIs (i.e. hand-washing and sanitizing surfaces), copper components don’t require human intervention or compliance to be effective.

“It supplements what these other things can do; it’s in the background and it’s always working,” Michels says.

A study needs to be done on the cost-effectiveness of copper surfaces. Health economists estimate that if copper surfaces were incorporated into ICUs, after three to six months, those surfaces would pay for themselves. That is not a long time period. Hospitals need to understand that there will be upfront costs but that they will realize benefits downstream.

—Cassandra D. Salgado, MD, associate professor of medicine, hospital epidemiologist, medical director for infection prevention, Medical University of South Carolina, Charleston

Study Specifics

To conduct the study, copper prototypes of items touched most frequently by patients, health-care providers, and visitors were made and placed in patient rooms located within ICUs. “We placed the copper around the patient [much like a defensive perimeter] to reduce the likelihood that the health-care worker or visitor would introduce the infectious agent to the patient,” says the study’s lead investigator, Michael Schmidt, PhD, a professor and vice chair of MUSC’s department of microbiology and immunology.

Then, bacterial loads were measured on each object. For every study room, there was a control room without copper objects. Researchers were most interested in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). For a period of time, bacterial burdens were measured in both copper rooms and control rooms.

Results exceeded the researchers’ expectations. Although only 7% of the touch surfaces in each ICU were replaced with copper components, there were 58% fewer HAI cases. The rate of HAI and/or MRSA or VRE colonization in ICU rooms with copper-alloy surfaces was significantly lower than that in standard ICU rooms (0.071 versus 0.123). For HAIs only, the rate was reduced to 0.034 from 0.081.³

“We were pleasantly surprised with the reductions,” Dr. Salgado says. “We consistently saw a more than 50% reduction in HAIs in all study sites.”

Archelle Georgiou, MD, president of Georgiou Consulting LLC in Minneapolis and an advisor to the Copper Development Association, is an advocate for making the health-care system simpler and safer for consumers. She says copper is a “game-changer.”

“It’s a brand-new way of thinking about decreasing the number of HAIs,” she says.

Green Light?

In light of the study’s encouraging findings, hospitalist and infectious-disease specialist James Pile, MD, FACP, SFHM, vice chair of the Department of Hospital Medicine at Cleveland Clinic, says that although study results appear valid, “it didn’t provide any final answers.”

Dr. Georgiou

“It would be premature for a hospital to install copper based on this study,” he says, adding he didn’t find the study results surprising, because copper is known to have antimicrobial properties.

But, Dr. Pile says, the study did provide proof of concept and opens the door for larger, more definitive studies that will show if installing copper in hospital rooms is worthwhile.

“If future studies confirm earlier results, then hospitals should seriously consider copper installations,” he says.

Dr. Georgiou

Barriers to Implementation

Despite the promising outlook for copper in dramatically reducing HAIs, implantation of copper components is off to a slow start.

Negotiations with the Environmental Protection Agency, the federal agency with jurisdiction over public-health claims for antimicrobial surfaces, started in 2004. Testing started in 2005. Although federal registration was completed in February 2008, it wasn’t until late 2011 that all regulatory issues were resolved for manufacturers.

“The regulatory process created delays in educating hospitals and the public about copper’s effectiveness in killing certain bacteria,” Dr. Georgiou explains. “As a result, American manufacturers with the ability to make copper components weren’t developing products because they couldn’t sell them.”

Now that the regulatory issues have been resolved, U.S. manufacturers are beginning to make copper components. The first wave of commercial products came on the market in late 2011. Meanwhile, European countries have not been delayed and are well ahead of U.S. hospitals in implementing copper components.

Presently, nine U.S. hospitals have installed some form of copper components, including door hardware, cabinet pulls, sinks, stretchers, and IV poles, Michels reports.

Despite these advances, hospitals may be slow to incorporate copper components due to a variety of reasons:

Cost. Dr. Pile believes that cost will be the major barrier. “Installing copper surfaces won’t be cheap,” he says. “But, then again, HAIs are very costly. I think it will be more difficult to justify their existence if they can be prevented. If copper is effective in preventing HAIs, it would prove to be cost-effective over time.”

Dr. Salgado concurs. “A study needs to be done on the cost-effectiveness of copper surfaces,” she says. “Health economists estimate that if copper surfaces were incorporated into ICUs, after three to six months, those surfaces would pay for themselves. That is not a long time period. Hospitals need to understand that there will be upfront costs but that they will realize benefits downstream.”

The Center for Medicare & Medicaid Services (CMS) has reported that one infection adds $43,000 in patient costs.⁴ A typical U.S. hospital room contains $100,000 worth of goods and equipment.

“When you do the math using the amount of copper in our study, the cost would be between $1 and $10 per patient,” Dr. Schmidt says. “It’s also important to note that an infection adds 19 days to a patient’s hospital stay.”

Aesthetics. For some, appearance may be a concern. “Copper is actually an appealing material that is offered in an array of colors and surface finishes,” Dr. Michels says. Because a copper-and-brass combination is more prone to tarnishing, a copper-nickel alloy may be more desirable.

Availability. Copper components are not produced and marketed to U.S. hospitals; however, they are available. “We are hoping with our study and future studies that some medical-device companies, as well as hospital-furniture manufacturers, will jump on board to look at ways to mass-produce items,” Dr. Salgado says.

Acceptance. The study published in Infection Control and Hospital Epidemiology validated the effectiveness of copper in decreasing HAIs. This pilot study, however, was not blinded.³

“It was pretty apparent to providers where copper surfaces were located, which tends to result in some bias. Future studies will, hopefully, try to answer questions regarding healthcare providers’ behaviors with different surfaces,” says Dr. Salgado, noting researchers in California and Chile also are studying the effects of copper surfaces in hospitals.

Possible loss of efficacy. Even if a surface is effective initially, Dr. Pile points out that it’s possible for that to change. “I have a theoretical concern that, over time, bacterial pathogens may develop a tolerance to copper,” he says. “Bacterial adversaries have been able to overcome any type of treatment that we have devised for them thus far. But this remains to be seen.”

This has been an issue with other surfaces; once microbes establish a foothold, it is hard to eliminate them. But Dr. Schmidt says because bacteria are killed so quickly on copper surfaces and cleaning is only required once daily, the ability to establish a foothold is greatly reduced, if not completely eliminated.

Copper supplements what these other things can do; it’s in the background and it’s always working..

—Harold T. Michels, PhD, PE, senior vice president of technology and technical services, Copper Development Association Inc.

Champion Proven Strategies

Dr. Pile sees antimicrobial stewardship as a great opportunity for hospitalists as a specialty. In fact, the Centers for Disease Control and Prevention is partnering with HM groups on piloting multiple antimicrobial stewardship initiatives at several sites.

Dr. Pile suggests that leaders spearhead formal quality-improvement efforts, be involved with patient-safety efforts, and serve as physician champions.

“No one is better positioned to do this than hospitalists, because we own the hospital environment,” he says. “We have an incredible stake in making sure that our inpatient environment provides safe and high-value care.”

As a result of the published study, Dr. Salgado says discussions are underway with hospital leaders at MUSC to determine if copper surfaces will be used in its ICUs and, if so, how changes will be implemented.

Karen Appold is a freelance writer in Pennsylvania.

References

1. Klevens RM, Edwards JR, Richards CL, et al. Estimating healthcare-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep. 2007;122:160-166.
2. Scott RD. The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of Prevention. Atlanta: Centers for Disease Control and Prevention, 2009.
3. Salgado CD, Sepkowitz KA, John JF, et al. Copper Surfaces Reduce the Rate of Healthcare-Acquired Infections in the Intensive Care Unit. Infect Control Hosp Epidemiol. 2013;34(5):479-486.
4. Healthcare Cost and Utilization Project. Statistical Brief No. 94. Agency for Healthcare Research and Quality. Aug. 2010. Available at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb94.pdf. Accessed Aug. 6, 2013.

The term amyloidosis refers to a fascinating group of disorders that share a common pathogenesis of extracellular deposition of amyloid material. Fundamentally, it is a disorder of the secondary structure of select proteins whereby the amyloidogenic proteins are misfolded into a β-pleated sheet configuration, resulting in the formation of insoluble extracellular amyloid fibrils. The amyloid fibrils appear as amorphous eosinophilic material when hematoxylin and eosin–stained tissue is examined under light microscope. Electron microscopy reveals remarkable similarity between the amyloid fibrils derived from different precursor proteins in that they range from 7.5 to 10 nm in diameter. This ultrastructural similarity is the underlying basis for the characteristic red-green birefringence with Congo red staining observed under polarized microscopy, the pathological hallmark of the disease.

To read the full article in PDF:

Click here

The term amyloidosis refers to a fascinating group of disorders that share a common pathogenesis of extracellular deposition of amyloid material. Fundamentally, it is a disorder of the secondary structure of select proteins whereby the amyloidogenic proteins are misfolded into a β-pleated sheet configuration, resulting in the formation of insoluble extracellular amyloid fibrils. The amyloid fibrils appear as amorphous eosinophilic material when hematoxylin and eosin–stained tissue is examined under light microscope. Electron microscopy reveals remarkable similarity between the amyloid fibrils derived from different precursor proteins in that they range from 7.5 to 10 nm in diameter. This ultrastructural similarity is the underlying basis for the characteristic red-green birefringence with Congo red staining observed under polarized microscopy, the pathological hallmark of the disease.

To read the full article in PDF:

Click here

The term amyloidosis refers to a fascinating group of disorders that share a common pathogenesis of extracellular deposition of amyloid material. Fundamentally, it is a disorder of the secondary structure of select proteins whereby the amyloidogenic proteins are misfolded into a β-pleated sheet configuration, resulting in the formation of insoluble extracellular amyloid fibrils. The amyloid fibrils appear as amorphous eosinophilic material when hematoxylin and eosin–stained tissue is examined under light microscope. Electron microscopy reveals remarkable similarity between the amyloid fibrils derived from different precursor proteins in that they range from 7.5 to 10 nm in diameter. This ultrastructural similarity is the underlying basis for the characteristic red-green birefringence with Congo red staining observed under polarized microscopy, the pathological hallmark of the disease.

To read the full article in PDF:

Click here

Each year in the United States, more than 8 million people come to the emergency department with chest pain, but only a minority are eventually diagnosed with a heart attack.¹

Confronted with signs and symptoms that could represent an acute coronary syndrome, clinicians need to know whether the patient has a benign condition and can safely be sent home or is in urgent need of hospitalization—and they need to do so in a safe, timely, and cost-effective manner.^2,3

Testing for biomarkers of cardiac injury, especially troponins I and T, is an accepted part of the assessment of chest pain. However, the interpretation of these cardiac biomarkers is complicated by the fact they can be elevated from noncoronary causes of chest pain such as pulmonary embolism or renal impairment, and thus should be considered only as part of the patient’s total clinical picture. This uncertainty can result in longer hospital stays and increased testing.

Thus, researchers are searching for new biomarkers that could allow for more rapid and accurate diagnosis and estimation of prognosis.

In this article we will examine the advantages and limitations of measuring cardiac biomarkers. We then discuss the emerging data on new biomarkers, including the very promising high-sensitivity troponin assays, cystatin C, and other markers, and the potential for biomarkers to be used instead of or in combination with stress testing in the evaluation of patients who have no initial evidence of ischemia.

SCENARIO 1: ELEVATED TROPONIN AND ST-SEGMENT ELEVATION

A 46-year-old woman presents to the emergency department with chest pain that started 2 hours earlier. Electrocardiography (ECG) initially shows sinus tachycardia with ST-segment depression and negative T waves in lead aVL. Her cardiac biomarker values (troponin I and creatine kinase MB) are normal. Repeated troponin I measurements show elevations of 250 ng/L, whereas her creatine kinase MB level is within the optimal range. Coronary angiography is unremarkable. Echocardiography shows right ventricular pressure overload in the pulmonary artery and the right ventricle. How should this patient be further evaluated?

SCENARIO 2: ELEVATED TROPONIN AND LEFT VENTRICULAR HYPERTROPHY

A 47-year-old man is admitted with worsening dyspnea and chest pain that worsens with coughing and inspiration. He has a history of end-stage renal disease secondary to poorly controlled hypertension and is being treated with hemodialysis, which he missed for the past 4 weeks while failing to take his hypertension medication. His blood pressure is 270/130 mm Hg. Chest auscultation reveals signs of pulmonary edema—ie, crackles at the end of inspiration. His troponin T level is 394 ng/L. ECG indicates left ventricular hypertrophy. How should this patient be further evaluated?

TROPONIN IS SPECIFIC FOR INJURY, BUT NOT FOR INFARCTION

American College of Cardiology and American Heart Association (ACC/AHA) guidelines⁴ recommend that clinicians ask themselves two questions: what is the likelihood that the patient is truly having an acute coronary syndrome secondary to coronary artery disease, and what is the likelihood of an adverse clinical outcome? Clues come from the initial measurements of biomarkers of cardiac injury, history, physical examination, and ECG (Table 1),⁵ and subsequent care is based on the estimated degree of risk.

Troponin revolutionized the diagnosis and risk stratification of chest pain. The ACC/AHA guidelines call for measuring biomarkers—preferably troponin—in all patients who present with chest discomfort consistent with an acute coronary syndrome.^4,6

Cardiac troponins I and T have been the biomarkers of choice for detecting myocardial injury,^4,6 since elevated concentrations are highly sensitive and tissue-specific.⁷ Moreover, they identify patients at short-term and long-term risk of cardiac events.^4,8

The introduction of troponin testing led to a substantial increase in the rate of diagnosis of myocardial infarction (MI), with an increase in cardiac care unit admissions of more than 20%.^9,10 This was partly because troponin is released into the blood with even minute myocardial damage, so that some patients who previously would have been diagnosed with unstable angina are now found to have non-ST-segment-elevation MI.¹⁰ However, the increase in admissions may also represent an increase in misdiagnoses, with many clinicians equating an elevated troponin level with acute MI.¹¹

Although an elevated troponin level is 100% specific for myocardial injury, it is not synonymous with MI.¹² Myocardial injury can be caused by a cardiac condition such as tachyarrhythmia, cardiac trauma, congestive heart failure, ventricular hypertrophy, myocarditis, or pericarditis, or by a noncardiac condition such as sepsis, respiratory failure, pulmonary embolism, pulmonary hypertension, cancer chemotherapy, or renal insufficiency.^4,13 Therefore, to avoid a misdiagnosis of MI, the troponin level must be considered in the clinical context.

In fact, Alcalai et al¹¹ noted that almost half of patients with elevated troponin did not really have an acute coronary syndrome. More importantly, in-hospital and long-term survival rates were significantly better for patients with an acute coronary syndrome than for those without, illustrating the importance of identifying and treating the true disease instead of mislabeling the problem as MI.

Bayesian theory predicts that patients with chest pain who have elevated troponin are less likely to truly have an acute coronary syndrome if the rest of their clinical presentation indicates a low probability for heart disease.¹⁴ Indeed, when McDonald et al¹⁵ used a risk-scoring index based on sex, a history of heart failure or coronary artery disease, the ECG, and use of aspirin, the positive predictive value of an abnormal troponin level was 83% at a risk score of 4 or greater, 63% at a score of 3, 52% at a score of 2, 32% at a score of 1, and 29% at a score of 0.

Thus, cardiac biomarkers are not a substitute for traditional clinical assessment, but rather should be used “in conjunction with the clinical history, physical examination, and interpretation of the ECG.”⁶ Consequently, diagnostic protocols that incorporate pretest clinical features to identify low-risk patients have a higher negative predictive value.

This was illustrated in a study by Than et al¹⁶ that aimed to prospectively validate the safety of an accelerated diagnostic protocol to assess chest pain suggestive of an acute coronary syndrome. The protocol included a structured pretest probability scoring method (ie, the Thrombolysis in Myocardial Infarction [TIMI] score), ECG, and a point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The protocol had a negative predictive value of 99.1%, whereas the use of biomarkers alone had a value of 96.1%.

HISTORY AND PHYSICAL EXAMINATION PROVIDE KEY INFORMATION

In a review, Heidenreich et al⁸ noted certain demographic characteristics associated with worse outcomes—ie, older age and male sex; a history of medical conditions such as diabetes, MI, and hypertension; and heart failure on presentation.

A careful assessment of chest pain and associated symptoms helps narrow the differential diagnosis. Features that increase the likelihood of a cardiac origin of chest pain are:

• Chest pain at the time of presentation (likelihood ratio [LR] = 2.0)
• Radiation of the pain to the right shoulder (LR = 2.9), the left arm (LR = 2.3), or both arms (LR = 7.1)
• Nausea or vomiting (LR = 1.9)
• Diaphoresis (LR = 2.0).¹⁷

The physical examination can detect highrisk features such as new murmurs, hypotension, diaphoresis, pulmonary edema, and rales. It is more specific than sensitive and is useful in identifying low-risk patients by targeting potential noncardiac causes of the patient’s symptoms.¹⁸

The efficacy of clinical assessment was studied in 2,271 patients with chest pain presenting to the emergency department.¹⁹ In this cohort, a low-risk group with a 30-day major cardiovascular event rate (death, MI, stroke, or revascularization) of 2.5% could be identified through the use of the US Agency for Health Care Policy and Research criteria.

Electrocardiography

ECG provides important diagnostic and prognostic information and independently predicts death or MI, even after adjustment for cardiac biomarker measurements,^20,21 making it pivotal in the evaluation.⁴ The key features on ECG that increase the probability of MI are:

• New ST-segment elevation (LR 5.7–53.9)
• New Q waves (LR 5.3–24.8).¹⁷

One study²⁰ found that while the troponin T level was a powerful independent marker in patients presenting with MI, its value for risk stratification was enhanced when it was combined with a standard measure such as ECG.²⁰ While more than 90% of patients with STsegment elevation had an adverse outcome, only 31.7% of those patients had an elevated troponin T level.

No component is sufficient by itself

Thus, in spite of the proliferation of cardiac diagnostic tests, the initial bedside assessment of chest pain remains paramount. In fact, in patients presenting to the emergency department with chest pain, low risk (ie, those with a < 5% probability of MI) may be identified by presenting symptoms, medical history, and ECG alone.¹⁹

Furthermore, although clinical assessment, ECG, and cardiac biomarker testing each provide incremental benefit in assessing chest pain, no component is sufficient by itself. Sanchis et al²² found that even in patients with a normal troponin I level, the risk remained high in the case of ST-segment depression, and that even without signs of ischemia, the probability of cardiac events was 16% when the chest pain score was 11 points or higher.²² Consequently, a normal troponin level, ECG, or any other predictor alone would not ensure a good prognosis.

BIOMARKERS INSTEAD OF STRESS TESTING?

The ACC/AHA guidelines for the diagnosis of patients with unstable angina and non-STsegment elevation MI say that stable patients at low risk with no evidence of ischemia on initial assessment can be admitted to a chest pain unit for observation with serial cardiac biomarkers and ECG.⁴ At the end of the observation period, those who have reassuring results on ECG and normal cardiac biomarker measurements undergo functional cardiac testing or stress testing, or both.⁴

Exercise treadmill testing is a cornerstone of confirmatory testing in an accelerated diagnostic protocol because it is readily available, safe, and easy to do.¹⁸ A low-risk result was shown to have a high negative predictive value,^23,24 so that the likelihood of an acute coronary syndrome is low enough for safe discharge.

However, the overall process is not ideal since it is time-consuming, generates additional costs, and can have false-positive results in patients who are otherwise deemed not to be at high risk. While some studies provided an optimistic view about discharging low-risk patients with negative biomarkers without stress testing,^7,25 others have discouraged omitting exercise treadmill testing from protocols.^22,26

Others have proposed combining a biomarker with an imaging study such as coronary computed tomographic (CT) angiography.²⁷ Normal findings on this study have been shown to have a negative predictive value of up to 100% for ruling out an acute coronary syndrome and the occurrence of major adverse cardiovascular events in the long term.^28,29 Furthermore, it allows more-inclusive assessments of chest pain and can exclude other life-threatening causes such as pulmonary embolism and aortic dissection (referred to as the “triple rule-out”).³⁰

However, 25% to 50% of patients presenting to the emergency department with chest pain may not be candidates for CT angiography because of obesity, contrast allergy, intolerance to beta-blockade, arrhythmia, renal insufficiency, or a history of coronary artery disease.¹⁸ Moreover, it may be more efficient and less costly to discharge some patients without coronary CT angiography³¹ with the help of novel biomarkers without routine additional testing. This may spare patients the additional radiation exposure from CT angiography or nuclear imaging.^27,32

New biomarkers may, it is hoped, better distinguish patients at low risk from those at high risk without resorting to stress testing. Several of these markers are moving toward mainstream clinical use. For a biomarker to be prognostically equivalent to stress testing, it must be able to tell us if the likelihood of an acute coronary syndrome is low enough for safe discharge—ie, it must have a significantly high negative predictive value. Also, it must be an independent predictor of adverse outcomes, particularly in patients deemed at low risk by initial low troponin measurements. Biomarkers that have shown promise in this regard include high-sensitivity troponin, brain-type natriuretic peptide (BNP), cystatin C, and ischemia-modified albumin.

HIGH-SENSITIVITY CARDIAC TROPONIN ASSAYS

Although we speak of “high-sensitivity troponin,” these new assays detect the same molecule as do traditional troponin assays. The difference is that high-sensitivity assays can detect and measure troponin at concentrations much lower than the traditional assays can. In fact, high-sensitivity troponin assays can detect and measure troponin at very low levels in almost all healthy people.

Studies have shown that the high-sensitivity assays have better analytical accuracy and sensitivity than older assays.¹²

Aldous et al³³ reported that, in patients who presented to the emergency department within 4 hours of the onset of chest pain, an elevation in troponin T on a high-sensitivity assay had a positive predictive value of 53.8% and a negative predictive value of 98.3%.

Weber et al³⁴ found the diagnostic value of the high-sensitivity troponin T assay to be superior to that of a contemporary troponin T assay (area under the receiver-operating-characteristics curve [AUC] of 0.949 vs 0.929). Even when the contemporary troponin T assay was negative, the high-sensitivity assay provided strong diagnostic information (AUC 0.81). Furthermore, the high-sensitivity assay provided superior independent prognostic power for death within 6 months.

Hochholzer et al³⁵ reported a prognostic accuracy for death significantly higher (AUC 0.79) than that of contemporary troponin T (AUC 0.69). A concentration of high-sensitivity troponin T above 14 ng/L improved the prediction of death (hazard ratio 2.60) but not of subsequent acute MI in patients with acute chest pain. Therefore, a negative high-sensitivity troponin T assay identifies patients with a good prognosis and who may be discharged without further testing if their clinical presentation and ECG are also reassuring.

Keller et al³⁶ compared the diagnostic performance of the high-sensitivity cardiac troponin I assay against 11 other biomarkers, including a contemporary cardiac troponin I assay. The contemporary troponin I and the high-sensitivity troponin I assays performed best. The high-sensitivity troponin I assay at admission had a sensitivity of 82.3% and a negative predictive value of 94.7% for ruling out acute MI, whereas the contemporary troponin I assay had a sensitivity of 79.4% and a negative predictive value of 94.0%.

Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both troponin I assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value for ruling in acute MI for high-sensitivity cardiac troponin I increased from 75.1% at admission to 95.8% after 3 hours; for the contemporary assay, it increased from 80.9% at admission to 96.1%.³⁶

The authors concluded that performing either of the cardiac troponin I assays 3 hours after admission may help in ruling out MI early on, with a negative predictive value greater than 99%. Moreover, the relative change in concentration within the 3 hours after admission, combined with the 99th percentile diagnostic cutoff value on admission, improves specificity, allowing acute MI to be accurately ruled in.³⁶

Of note, though studies have confirmed that a measurement at 3 hours identifies most cases of MI early, they have not used the recommended maximal sensitivity interval for troponin measurements (6 hours or more).⁶

A proposed algorithm for diagnosing acute MI with a high-sensitivity assay

While high-sensitivity troponin T assays can improve the early diagnosis of acute MI, how best to use them is yet to be defined. They still lack specificity for acute coronary syndromes, with positive predictive values as low as 50%.³⁷

Reichlin et al³⁸ developed and validated an algorithm for rapidly ruling out or ruling in acute MI using a high-sensitivity cardiac troponin T assay, incorporating baseline values and absolute changes within the first hour. Using a baseline threshold of 12 ng/L or less and an absolute change of 3 ng/L or less, they found a sensitivity and negative predictive value of 100%, making these good criteria for ruling out acute MI.

Using a baseline threshold of 60 ng/L or greater and a change from baseline to 1 hour of at least 15 ng/L, the specificity was 97% and the positive predictive value was 84%, making these good criteria for ruling in acute MI.

Patients whose values were in between were classified as being in an “observationalzone group,” in which the prevalence of acute MI was 8%. The cumulative 30-day survival rate was 99.8% in patients in whom the test ruled out MI, 98.6% in the observational-zone patients, and 95.3% in patients in whom the test ruled in MI.³⁸ Using this simple algorithm allowed a safe rule-out as well as an accurate rule-in of acute MI within 1 hour in 77% of unselected patients with acute chest pain; thus, it may obviate the need for prolonged monitoring and serial measurements in three out of four patients.”

Newby³⁹ stated that such an algorithmic approach must be validated in a prospective study that assesses not only sensitivity, negative predictive value, specificity, and positive predictive value, but also the implications for clinical outcomes and the cost of widespread implementation.

In the meantime, clinicians must keep in mind that patient populations in clinical practice are less selected, the prevalence of MI may broadly vary, and confounding comorbidities such as heart failure and renal insufficiency are more common. Studies are also needed to verify whether other factors such as age, sex, and time from symptom onset should be considered.

BRAIN-TYPE NATRIURETIC PEPTIDE

BNP is a 32-amino-acid natriuretic peptide that is released from myocytes. The amount released depends on wall stress brought on by heart failure, ischemic heart disease, or other conditions.

In a study of the diagnostic utility of BNP in the workup of acute chest pain, Haaf et al⁴⁰ found that BNP levels at presentation were significantly higher in patients with acute MI than in patients with other diagnoses. However, the diagnostic accuracy of BNP was lower than that of cardiac troponin T at presentation, though its independent predictive value for all-cause mortality was more accurate than that of troponin T.

Elevation of the BNP ⁴¹ or the N-terminal pro-BNP ^42,43 level was shown to also provide unique prognostic information in patients with suspected and confirmed acute coronary syndrome and was associated with higher rates of short-term and long-term mortality. Therefore, BNP appears useful for the prognosis but not the diagnosis of acute coronary syndromes.

CYSTATIN C

The protein cystatin C, widely used as a biomarker for kidney disease, has more recently been touted as a prognostic marker in acute coronary syndromes.

Jernberg et al⁴⁴ reported that, in patients with a suspected or confirmed acute coronary syndrome, a single measurement of cystatin C significantly improved the early stratification of risk.⁴⁴ Specifically, the cystatin C level was independently associated with mortality risk but not with the risk of subsequent MI.

In another study,⁴⁵ the cystatin C concentration independently predicted the risk of cardiovascular death or MI in non-ST-segment elevation acute coronary syndrome. However, the additive predictive value of cystatin C in these patients was found to be small when clinical risk factors and biomarkers of MI were used in the prediction model. Therefore, cystatin C may predict global risk but does not appear to be useful in diagnosing MI.

ISCHEMIA-MODIFIED ALBUMIN

A major limitation of troponin is that it cannot detect reversible myocardial ischemia in the absence of cardiac necrosis, making stress testing necessary to unmask potential reversible ischemia.

Ischemia-modified albumin has been proposed as a means of detecting cardiac ischemia even if necrosis is absent. It is a product of the N-terminus alteration of albumin caused by myocardial ischemia, which reduces the ability of cobalt to bind to albumin and can be detected with the albumin cobalt binding test. This marker might have a high negative predictive value, ruling out acute coronary syndromes in conditions of low pretest probability with negative necrosis markers and ECG.^13,46

Although ischemia-modified albumin does show promise, doubt remains as to its validity as a biomarker, as its mechanism of generation is not known. Some have suggested that it is in fact a marker of oxidative stress.⁴⁷

PANELS OF MARKERS

The individual biomarkers we have discussed here have advantages and limitations in the emergency workup of chest pain. The concept of using a multimarker panel has been raised as a way of amplifying the positive attributes of individual biomarkers and compensating for their shortcomings.

Sabatine et al⁴⁸ tested this approach in patients with acute coronary syndromes who were at high risk of an adverse outcome. When patients were categorized at presentation on the basis of the number of elevated biomarkers such as cardiac troponin I, C-reactive protein, and BNP, the risk of death nearly doubled with each additional biomarker that was elevated.

The relationship was similar for the end points of MI, heart failure, and the composite at 30 days and 10 months. In a cohort of 1,635 patients, the number of elevated biomarkers remained a predictor of the composite end point after adjustment for known clinical predictors. The risk of death, MI, or heart failure by 6 months was 2.1 times higher in patients with one elevated biomarker, 3.1 times higher in those with two, and 3.7 times higher in those with three.

The authors concluded that a multimarker strategy that categorizes patients on the basis of the number of elevated biomarkers at presentation allows risk-stratification of short- and long-term cardiac events.

Tello-Montoliu et al⁴⁹ tested this idea in patients with non-ST-segment elevation acute coronary syndromes using a panel consisting of cardiac troponin T, C-reactive protein, N-terminal pro-BNP, and fibrin D-dimer. The risk of a major event (death, new acute coronary syndrome, revascularization, or heart failure) at 6 months was associated with abnormal biomarker levels, especially with the presence of three positive biomarkers, even after adjustment for clinical characteristics and ECG findings.

van der Zee et al⁴³ showed that a positive biomarker panel consisting of C-reactive protein and N-terminal pro-BNP identified patients with chest pain and a normal or nondiagnostic ECG who have a high long-term risk of cardiovascular death.

Glaser et al⁵⁰ evaluated the combination of cardiac troponin I, BNP, homocysteine, C-reactive protein, placental growth factor, myeloperoxidase, choline, soluble CD40 ligand, ischemia-modified albumin, and lipoprotein-associated phospholipase A2 in patients with a suspected acute coronary syndrome. The combination of BNP, placental growth factor, and estimated glomerular filtration rate was the most accurate predictor of major adverse cardiovascular events compared with any other biomarker or clinical factor. With appropriate cutoff values, the negative predictive value for a major adverse cardiovascular event at 1 year was as high as 99.1%.

This study highlighted the importance of combining biomarkers, showing that with a negative predictive value of 97% for 30-day events, the combination of placental growth factor, BNP, and cardiac troponin I may help surmount the delay from symptom onset to cardiac troponin increase, thus permitting a more timely diagnosis and safe discharge within 12 hours.

Comment. These studies raise the promise that panels of biomarkers can be used in patients deemed to be at low risk after clinical assessment and troponin evaluation to enable them to be safely discharged early and to obviate the need for stress testing.

If we assume that unstable cardiac disease requiring hospitalization accounts for 35% of patients with chest pain, a hypothetical panel of biomarkers with a sensitivity and specificity of 95% for adverse cardiac outcomes would have a positive predictive value of 91% and a negative predictive value of 97%. The negative likelihood ratio of this hypothetical biomarker panel would be 0.05, while the positive likelihood ratio would be 19. This performance level means that in patients with a pretest probability less than 50%, the posttest probability can be reduced to below 10%, so that such patients can be safely discharged without further hospital evaluation.

Conversely, a positive test result in patients with pretest probability of 30% or greater raises the posttest probability to nearly 90%, meaning that such patients should be considered for aggressive intervention without the need for stress testing.

RETURN TO OUR SCENARIOS

Chest pain remains a nonspecific complaint, and the interpretation of biomarkers to find the cause presents clinicians with challenges, as illustrated by the cases introduced at the beginning of this article.

The cardiac troponin I elevation in scenario 1 led to an initial diagnosis of unstable angina. However, coronary angiography showed lesion-free coronary arteries, thus excluding ischemic heart disease. When other diseases that could cause elevated cardiac troponin I were considered and investigated with further diagnostic tests such as D-dimer, pulmonary embolism became the new working diagnosis, and this was confirmed by CT angiography.

Similarly, given the laboratory values for the patient in scenario 2, the condition could have been mistaken for an acute coronary syndrome. However, the absence of evidence on ECG to support this diagnosis would indicate an erroneously elevated biomarker secondary to his background of chronic renal insufficiency.

Each year in the United States, more than 8 million people come to the emergency department with chest pain, but only a minority are eventually diagnosed with a heart attack.¹

Confronted with signs and symptoms that could represent an acute coronary syndrome, clinicians need to know whether the patient has a benign condition and can safely be sent home or is in urgent need of hospitalization—and they need to do so in a safe, timely, and cost-effective manner.^2,3

Testing for biomarkers of cardiac injury, especially troponins I and T, is an accepted part of the assessment of chest pain. However, the interpretation of these cardiac biomarkers is complicated by the fact they can be elevated from noncoronary causes of chest pain such as pulmonary embolism or renal impairment, and thus should be considered only as part of the patient’s total clinical picture. This uncertainty can result in longer hospital stays and increased testing.

Thus, researchers are searching for new biomarkers that could allow for more rapid and accurate diagnosis and estimation of prognosis.

In this article we will examine the advantages and limitations of measuring cardiac biomarkers. We then discuss the emerging data on new biomarkers, including the very promising high-sensitivity troponin assays, cystatin C, and other markers, and the potential for biomarkers to be used instead of or in combination with stress testing in the evaluation of patients who have no initial evidence of ischemia.

SCENARIO 1: ELEVATED TROPONIN AND ST-SEGMENT ELEVATION

A 46-year-old woman presents to the emergency department with chest pain that started 2 hours earlier. Electrocardiography (ECG) initially shows sinus tachycardia with ST-segment depression and negative T waves in lead aVL. Her cardiac biomarker values (troponin I and creatine kinase MB) are normal. Repeated troponin I measurements show elevations of 250 ng/L, whereas her creatine kinase MB level is within the optimal range. Coronary angiography is unremarkable. Echocardiography shows right ventricular pressure overload in the pulmonary artery and the right ventricle. How should this patient be further evaluated?

SCENARIO 2: ELEVATED TROPONIN AND LEFT VENTRICULAR HYPERTROPHY

A 47-year-old man is admitted with worsening dyspnea and chest pain that worsens with coughing and inspiration. He has a history of end-stage renal disease secondary to poorly controlled hypertension and is being treated with hemodialysis, which he missed for the past 4 weeks while failing to take his hypertension medication. His blood pressure is 270/130 mm Hg. Chest auscultation reveals signs of pulmonary edema—ie, crackles at the end of inspiration. His troponin T level is 394 ng/L. ECG indicates left ventricular hypertrophy. How should this patient be further evaluated?

TROPONIN IS SPECIFIC FOR INJURY, BUT NOT FOR INFARCTION

American College of Cardiology and American Heart Association (ACC/AHA) guidelines⁴ recommend that clinicians ask themselves two questions: what is the likelihood that the patient is truly having an acute coronary syndrome secondary to coronary artery disease, and what is the likelihood of an adverse clinical outcome? Clues come from the initial measurements of biomarkers of cardiac injury, history, physical examination, and ECG (Table 1),⁵ and subsequent care is based on the estimated degree of risk.

Troponin revolutionized the diagnosis and risk stratification of chest pain. The ACC/AHA guidelines call for measuring biomarkers—preferably troponin—in all patients who present with chest discomfort consistent with an acute coronary syndrome.^4,6

Cardiac troponins I and T have been the biomarkers of choice for detecting myocardial injury,^4,6 since elevated concentrations are highly sensitive and tissue-specific.⁷ Moreover, they identify patients at short-term and long-term risk of cardiac events.^4,8

The introduction of troponin testing led to a substantial increase in the rate of diagnosis of myocardial infarction (MI), with an increase in cardiac care unit admissions of more than 20%.^9,10 This was partly because troponin is released into the blood with even minute myocardial damage, so that some patients who previously would have been diagnosed with unstable angina are now found to have non-ST-segment-elevation MI.¹⁰ However, the increase in admissions may also represent an increase in misdiagnoses, with many clinicians equating an elevated troponin level with acute MI.¹¹

Although an elevated troponin level is 100% specific for myocardial injury, it is not synonymous with MI.¹² Myocardial injury can be caused by a cardiac condition such as tachyarrhythmia, cardiac trauma, congestive heart failure, ventricular hypertrophy, myocarditis, or pericarditis, or by a noncardiac condition such as sepsis, respiratory failure, pulmonary embolism, pulmonary hypertension, cancer chemotherapy, or renal insufficiency.^4,13 Therefore, to avoid a misdiagnosis of MI, the troponin level must be considered in the clinical context.

In fact, Alcalai et al¹¹ noted that almost half of patients with elevated troponin did not really have an acute coronary syndrome. More importantly, in-hospital and long-term survival rates were significantly better for patients with an acute coronary syndrome than for those without, illustrating the importance of identifying and treating the true disease instead of mislabeling the problem as MI.

Bayesian theory predicts that patients with chest pain who have elevated troponin are less likely to truly have an acute coronary syndrome if the rest of their clinical presentation indicates a low probability for heart disease.¹⁴ Indeed, when McDonald et al¹⁵ used a risk-scoring index based on sex, a history of heart failure or coronary artery disease, the ECG, and use of aspirin, the positive predictive value of an abnormal troponin level was 83% at a risk score of 4 or greater, 63% at a score of 3, 52% at a score of 2, 32% at a score of 1, and 29% at a score of 0.

Thus, cardiac biomarkers are not a substitute for traditional clinical assessment, but rather should be used “in conjunction with the clinical history, physical examination, and interpretation of the ECG.”⁶ Consequently, diagnostic protocols that incorporate pretest clinical features to identify low-risk patients have a higher negative predictive value.

This was illustrated in a study by Than et al¹⁶ that aimed to prospectively validate the safety of an accelerated diagnostic protocol to assess chest pain suggestive of an acute coronary syndrome. The protocol included a structured pretest probability scoring method (ie, the Thrombolysis in Myocardial Infarction [TIMI] score), ECG, and a point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The protocol had a negative predictive value of 99.1%, whereas the use of biomarkers alone had a value of 96.1%.

HISTORY AND PHYSICAL EXAMINATION PROVIDE KEY INFORMATION

In a review, Heidenreich et al⁸ noted certain demographic characteristics associated with worse outcomes—ie, older age and male sex; a history of medical conditions such as diabetes, MI, and hypertension; and heart failure on presentation.

A careful assessment of chest pain and associated symptoms helps narrow the differential diagnosis. Features that increase the likelihood of a cardiac origin of chest pain are:

• Chest pain at the time of presentation (likelihood ratio [LR] = 2.0)
• Radiation of the pain to the right shoulder (LR = 2.9), the left arm (LR = 2.3), or both arms (LR = 7.1)
• Nausea or vomiting (LR = 1.9)
• Diaphoresis (LR = 2.0).¹⁷

The physical examination can detect highrisk features such as new murmurs, hypotension, diaphoresis, pulmonary edema, and rales. It is more specific than sensitive and is useful in identifying low-risk patients by targeting potential noncardiac causes of the patient’s symptoms.¹⁸

The efficacy of clinical assessment was studied in 2,271 patients with chest pain presenting to the emergency department.¹⁹ In this cohort, a low-risk group with a 30-day major cardiovascular event rate (death, MI, stroke, or revascularization) of 2.5% could be identified through the use of the US Agency for Health Care Policy and Research criteria.

Electrocardiography

ECG provides important diagnostic and prognostic information and independently predicts death or MI, even after adjustment for cardiac biomarker measurements,^20,21 making it pivotal in the evaluation.⁴ The key features on ECG that increase the probability of MI are:

• New ST-segment elevation (LR 5.7–53.9)
• New Q waves (LR 5.3–24.8).¹⁷

One study²⁰ found that while the troponin T level was a powerful independent marker in patients presenting with MI, its value for risk stratification was enhanced when it was combined with a standard measure such as ECG.²⁰ While more than 90% of patients with STsegment elevation had an adverse outcome, only 31.7% of those patients had an elevated troponin T level.

No component is sufficient by itself

Thus, in spite of the proliferation of cardiac diagnostic tests, the initial bedside assessment of chest pain remains paramount. In fact, in patients presenting to the emergency department with chest pain, low risk (ie, those with a < 5% probability of MI) may be identified by presenting symptoms, medical history, and ECG alone.¹⁹

Furthermore, although clinical assessment, ECG, and cardiac biomarker testing each provide incremental benefit in assessing chest pain, no component is sufficient by itself. Sanchis et al²² found that even in patients with a normal troponin I level, the risk remained high in the case of ST-segment depression, and that even without signs of ischemia, the probability of cardiac events was 16% when the chest pain score was 11 points or higher.²² Consequently, a normal troponin level, ECG, or any other predictor alone would not ensure a good prognosis.

BIOMARKERS INSTEAD OF STRESS TESTING?

The ACC/AHA guidelines for the diagnosis of patients with unstable angina and non-STsegment elevation MI say that stable patients at low risk with no evidence of ischemia on initial assessment can be admitted to a chest pain unit for observation with serial cardiac biomarkers and ECG.⁴ At the end of the observation period, those who have reassuring results on ECG and normal cardiac biomarker measurements undergo functional cardiac testing or stress testing, or both.⁴

Exercise treadmill testing is a cornerstone of confirmatory testing in an accelerated diagnostic protocol because it is readily available, safe, and easy to do.¹⁸ A low-risk result was shown to have a high negative predictive value,^23,24 so that the likelihood of an acute coronary syndrome is low enough for safe discharge.

However, the overall process is not ideal since it is time-consuming, generates additional costs, and can have false-positive results in patients who are otherwise deemed not to be at high risk. While some studies provided an optimistic view about discharging low-risk patients with negative biomarkers without stress testing,^7,25 others have discouraged omitting exercise treadmill testing from protocols.^22,26

Others have proposed combining a biomarker with an imaging study such as coronary computed tomographic (CT) angiography.²⁷ Normal findings on this study have been shown to have a negative predictive value of up to 100% for ruling out an acute coronary syndrome and the occurrence of major adverse cardiovascular events in the long term.^28,29 Furthermore, it allows more-inclusive assessments of chest pain and can exclude other life-threatening causes such as pulmonary embolism and aortic dissection (referred to as the “triple rule-out”).³⁰

However, 25% to 50% of patients presenting to the emergency department with chest pain may not be candidates for CT angiography because of obesity, contrast allergy, intolerance to beta-blockade, arrhythmia, renal insufficiency, or a history of coronary artery disease.¹⁸ Moreover, it may be more efficient and less costly to discharge some patients without coronary CT angiography³¹ with the help of novel biomarkers without routine additional testing. This may spare patients the additional radiation exposure from CT angiography or nuclear imaging.^27,32

New biomarkers may, it is hoped, better distinguish patients at low risk from those at high risk without resorting to stress testing. Several of these markers are moving toward mainstream clinical use. For a biomarker to be prognostically equivalent to stress testing, it must be able to tell us if the likelihood of an acute coronary syndrome is low enough for safe discharge—ie, it must have a significantly high negative predictive value. Also, it must be an independent predictor of adverse outcomes, particularly in patients deemed at low risk by initial low troponin measurements. Biomarkers that have shown promise in this regard include high-sensitivity troponin, brain-type natriuretic peptide (BNP), cystatin C, and ischemia-modified albumin.

HIGH-SENSITIVITY CARDIAC TROPONIN ASSAYS

Although we speak of “high-sensitivity troponin,” these new assays detect the same molecule as do traditional troponin assays. The difference is that high-sensitivity assays can detect and measure troponin at concentrations much lower than the traditional assays can. In fact, high-sensitivity troponin assays can detect and measure troponin at very low levels in almost all healthy people.

Studies have shown that the high-sensitivity assays have better analytical accuracy and sensitivity than older assays.¹²

Aldous et al³³ reported that, in patients who presented to the emergency department within 4 hours of the onset of chest pain, an elevation in troponin T on a high-sensitivity assay had a positive predictive value of 53.8% and a negative predictive value of 98.3%.

Weber et al³⁴ found the diagnostic value of the high-sensitivity troponin T assay to be superior to that of a contemporary troponin T assay (area under the receiver-operating-characteristics curve [AUC] of 0.949 vs 0.929). Even when the contemporary troponin T assay was negative, the high-sensitivity assay provided strong diagnostic information (AUC 0.81). Furthermore, the high-sensitivity assay provided superior independent prognostic power for death within 6 months.

Hochholzer et al³⁵ reported a prognostic accuracy for death significantly higher (AUC 0.79) than that of contemporary troponin T (AUC 0.69). A concentration of high-sensitivity troponin T above 14 ng/L improved the prediction of death (hazard ratio 2.60) but not of subsequent acute MI in patients with acute chest pain. Therefore, a negative high-sensitivity troponin T assay identifies patients with a good prognosis and who may be discharged without further testing if their clinical presentation and ECG are also reassuring.

Keller et al³⁶ compared the diagnostic performance of the high-sensitivity cardiac troponin I assay against 11 other biomarkers, including a contemporary cardiac troponin I assay. The contemporary troponin I and the high-sensitivity troponin I assays performed best. The high-sensitivity troponin I assay at admission had a sensitivity of 82.3% and a negative predictive value of 94.7% for ruling out acute MI, whereas the contemporary troponin I assay had a sensitivity of 79.4% and a negative predictive value of 94.0%.

Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both troponin I assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value for ruling in acute MI for high-sensitivity cardiac troponin I increased from 75.1% at admission to 95.8% after 3 hours; for the contemporary assay, it increased from 80.9% at admission to 96.1%.³⁶

The authors concluded that performing either of the cardiac troponin I assays 3 hours after admission may help in ruling out MI early on, with a negative predictive value greater than 99%. Moreover, the relative change in concentration within the 3 hours after admission, combined with the 99th percentile diagnostic cutoff value on admission, improves specificity, allowing acute MI to be accurately ruled in.³⁶

Of note, though studies have confirmed that a measurement at 3 hours identifies most cases of MI early, they have not used the recommended maximal sensitivity interval for troponin measurements (6 hours or more).⁶

A proposed algorithm for diagnosing acute MI with a high-sensitivity assay

While high-sensitivity troponin T assays can improve the early diagnosis of acute MI, how best to use them is yet to be defined. They still lack specificity for acute coronary syndromes, with positive predictive values as low as 50%.³⁷

Reichlin et al³⁸ developed and validated an algorithm for rapidly ruling out or ruling in acute MI using a high-sensitivity cardiac troponin T assay, incorporating baseline values and absolute changes within the first hour. Using a baseline threshold of 12 ng/L or less and an absolute change of 3 ng/L or less, they found a sensitivity and negative predictive value of 100%, making these good criteria for ruling out acute MI.

Using a baseline threshold of 60 ng/L or greater and a change from baseline to 1 hour of at least 15 ng/L, the specificity was 97% and the positive predictive value was 84%, making these good criteria for ruling in acute MI.

Patients whose values were in between were classified as being in an “observationalzone group,” in which the prevalence of acute MI was 8%. The cumulative 30-day survival rate was 99.8% in patients in whom the test ruled out MI, 98.6% in the observational-zone patients, and 95.3% in patients in whom the test ruled in MI.³⁸ Using this simple algorithm allowed a safe rule-out as well as an accurate rule-in of acute MI within 1 hour in 77% of unselected patients with acute chest pain; thus, it may obviate the need for prolonged monitoring and serial measurements in three out of four patients.”

Newby³⁹ stated that such an algorithmic approach must be validated in a prospective study that assesses not only sensitivity, negative predictive value, specificity, and positive predictive value, but also the implications for clinical outcomes and the cost of widespread implementation.

In the meantime, clinicians must keep in mind that patient populations in clinical practice are less selected, the prevalence of MI may broadly vary, and confounding comorbidities such as heart failure and renal insufficiency are more common. Studies are also needed to verify whether other factors such as age, sex, and time from symptom onset should be considered.

BRAIN-TYPE NATRIURETIC PEPTIDE

BNP is a 32-amino-acid natriuretic peptide that is released from myocytes. The amount released depends on wall stress brought on by heart failure, ischemic heart disease, or other conditions.

In a study of the diagnostic utility of BNP in the workup of acute chest pain, Haaf et al⁴⁰ found that BNP levels at presentation were significantly higher in patients with acute MI than in patients with other diagnoses. However, the diagnostic accuracy of BNP was lower than that of cardiac troponin T at presentation, though its independent predictive value for all-cause mortality was more accurate than that of troponin T.

Elevation of the BNP ⁴¹ or the N-terminal pro-BNP ^42,43 level was shown to also provide unique prognostic information in patients with suspected and confirmed acute coronary syndrome and was associated with higher rates of short-term and long-term mortality. Therefore, BNP appears useful for the prognosis but not the diagnosis of acute coronary syndromes.

CYSTATIN C

The protein cystatin C, widely used as a biomarker for kidney disease, has more recently been touted as a prognostic marker in acute coronary syndromes.

Jernberg et al⁴⁴ reported that, in patients with a suspected or confirmed acute coronary syndrome, a single measurement of cystatin C significantly improved the early stratification of risk.⁴⁴ Specifically, the cystatin C level was independently associated with mortality risk but not with the risk of subsequent MI.

In another study,⁴⁵ the cystatin C concentration independently predicted the risk of cardiovascular death or MI in non-ST-segment elevation acute coronary syndrome. However, the additive predictive value of cystatin C in these patients was found to be small when clinical risk factors and biomarkers of MI were used in the prediction model. Therefore, cystatin C may predict global risk but does not appear to be useful in diagnosing MI.

ISCHEMIA-MODIFIED ALBUMIN

A major limitation of troponin is that it cannot detect reversible myocardial ischemia in the absence of cardiac necrosis, making stress testing necessary to unmask potential reversible ischemia.

Ischemia-modified albumin has been proposed as a means of detecting cardiac ischemia even if necrosis is absent. It is a product of the N-terminus alteration of albumin caused by myocardial ischemia, which reduces the ability of cobalt to bind to albumin and can be detected with the albumin cobalt binding test. This marker might have a high negative predictive value, ruling out acute coronary syndromes in conditions of low pretest probability with negative necrosis markers and ECG.^13,46

Although ischemia-modified albumin does show promise, doubt remains as to its validity as a biomarker, as its mechanism of generation is not known. Some have suggested that it is in fact a marker of oxidative stress.⁴⁷

PANELS OF MARKERS

The individual biomarkers we have discussed here have advantages and limitations in the emergency workup of chest pain. The concept of using a multimarker panel has been raised as a way of amplifying the positive attributes of individual biomarkers and compensating for their shortcomings.

Sabatine et al⁴⁸ tested this approach in patients with acute coronary syndromes who were at high risk of an adverse outcome. When patients were categorized at presentation on the basis of the number of elevated biomarkers such as cardiac troponin I, C-reactive protein, and BNP, the risk of death nearly doubled with each additional biomarker that was elevated.

The relationship was similar for the end points of MI, heart failure, and the composite at 30 days and 10 months. In a cohort of 1,635 patients, the number of elevated biomarkers remained a predictor of the composite end point after adjustment for known clinical predictors. The risk of death, MI, or heart failure by 6 months was 2.1 times higher in patients with one elevated biomarker, 3.1 times higher in those with two, and 3.7 times higher in those with three.

The authors concluded that a multimarker strategy that categorizes patients on the basis of the number of elevated biomarkers at presentation allows risk-stratification of short- and long-term cardiac events.

Tello-Montoliu et al⁴⁹ tested this idea in patients with non-ST-segment elevation acute coronary syndromes using a panel consisting of cardiac troponin T, C-reactive protein, N-terminal pro-BNP, and fibrin D-dimer. The risk of a major event (death, new acute coronary syndrome, revascularization, or heart failure) at 6 months was associated with abnormal biomarker levels, especially with the presence of three positive biomarkers, even after adjustment for clinical characteristics and ECG findings.

van der Zee et al⁴³ showed that a positive biomarker panel consisting of C-reactive protein and N-terminal pro-BNP identified patients with chest pain and a normal or nondiagnostic ECG who have a high long-term risk of cardiovascular death.

Glaser et al⁵⁰ evaluated the combination of cardiac troponin I, BNP, homocysteine, C-reactive protein, placental growth factor, myeloperoxidase, choline, soluble CD40 ligand, ischemia-modified albumin, and lipoprotein-associated phospholipase A2 in patients with a suspected acute coronary syndrome. The combination of BNP, placental growth factor, and estimated glomerular filtration rate was the most accurate predictor of major adverse cardiovascular events compared with any other biomarker or clinical factor. With appropriate cutoff values, the negative predictive value for a major adverse cardiovascular event at 1 year was as high as 99.1%.

This study highlighted the importance of combining biomarkers, showing that with a negative predictive value of 97% for 30-day events, the combination of placental growth factor, BNP, and cardiac troponin I may help surmount the delay from symptom onset to cardiac troponin increase, thus permitting a more timely diagnosis and safe discharge within 12 hours.

Comment. These studies raise the promise that panels of biomarkers can be used in patients deemed to be at low risk after clinical assessment and troponin evaluation to enable them to be safely discharged early and to obviate the need for stress testing.

If we assume that unstable cardiac disease requiring hospitalization accounts for 35% of patients with chest pain, a hypothetical panel of biomarkers with a sensitivity and specificity of 95% for adverse cardiac outcomes would have a positive predictive value of 91% and a negative predictive value of 97%. The negative likelihood ratio of this hypothetical biomarker panel would be 0.05, while the positive likelihood ratio would be 19. This performance level means that in patients with a pretest probability less than 50%, the posttest probability can be reduced to below 10%, so that such patients can be safely discharged without further hospital evaluation.

Conversely, a positive test result in patients with pretest probability of 30% or greater raises the posttest probability to nearly 90%, meaning that such patients should be considered for aggressive intervention without the need for stress testing.

RETURN TO OUR SCENARIOS

Chest pain remains a nonspecific complaint, and the interpretation of biomarkers to find the cause presents clinicians with challenges, as illustrated by the cases introduced at the beginning of this article.

The cardiac troponin I elevation in scenario 1 led to an initial diagnosis of unstable angina. However, coronary angiography showed lesion-free coronary arteries, thus excluding ischemic heart disease. When other diseases that could cause elevated cardiac troponin I were considered and investigated with further diagnostic tests such as D-dimer, pulmonary embolism became the new working diagnosis, and this was confirmed by CT angiography.

Similarly, given the laboratory values for the patient in scenario 2, the condition could have been mistaken for an acute coronary syndrome. However, the absence of evidence on ECG to support this diagnosis would indicate an erroneously elevated biomarker secondary to his background of chronic renal insufficiency.

Each year in the United States, more than 8 million people come to the emergency department with chest pain, but only a minority are eventually diagnosed with a heart attack.¹

Confronted with signs and symptoms that could represent an acute coronary syndrome, clinicians need to know whether the patient has a benign condition and can safely be sent home or is in urgent need of hospitalization—and they need to do so in a safe, timely, and cost-effective manner.^2,3

Testing for biomarkers of cardiac injury, especially troponins I and T, is an accepted part of the assessment of chest pain. However, the interpretation of these cardiac biomarkers is complicated by the fact they can be elevated from noncoronary causes of chest pain such as pulmonary embolism or renal impairment, and thus should be considered only as part of the patient’s total clinical picture. This uncertainty can result in longer hospital stays and increased testing.

Thus, researchers are searching for new biomarkers that could allow for more rapid and accurate diagnosis and estimation of prognosis.

In this article we will examine the advantages and limitations of measuring cardiac biomarkers. We then discuss the emerging data on new biomarkers, including the very promising high-sensitivity troponin assays, cystatin C, and other markers, and the potential for biomarkers to be used instead of or in combination with stress testing in the evaluation of patients who have no initial evidence of ischemia.

SCENARIO 1: ELEVATED TROPONIN AND ST-SEGMENT ELEVATION

A 46-year-old woman presents to the emergency department with chest pain that started 2 hours earlier. Electrocardiography (ECG) initially shows sinus tachycardia with ST-segment depression and negative T waves in lead aVL. Her cardiac biomarker values (troponin I and creatine kinase MB) are normal. Repeated troponin I measurements show elevations of 250 ng/L, whereas her creatine kinase MB level is within the optimal range. Coronary angiography is unremarkable. Echocardiography shows right ventricular pressure overload in the pulmonary artery and the right ventricle. How should this patient be further evaluated?

SCENARIO 2: ELEVATED TROPONIN AND LEFT VENTRICULAR HYPERTROPHY

A 47-year-old man is admitted with worsening dyspnea and chest pain that worsens with coughing and inspiration. He has a history of end-stage renal disease secondary to poorly controlled hypertension and is being treated with hemodialysis, which he missed for the past 4 weeks while failing to take his hypertension medication. His blood pressure is 270/130 mm Hg. Chest auscultation reveals signs of pulmonary edema—ie, crackles at the end of inspiration. His troponin T level is 394 ng/L. ECG indicates left ventricular hypertrophy. How should this patient be further evaluated?

TROPONIN IS SPECIFIC FOR INJURY, BUT NOT FOR INFARCTION

American College of Cardiology and American Heart Association (ACC/AHA) guidelines⁴ recommend that clinicians ask themselves two questions: what is the likelihood that the patient is truly having an acute coronary syndrome secondary to coronary artery disease, and what is the likelihood of an adverse clinical outcome? Clues come from the initial measurements of biomarkers of cardiac injury, history, physical examination, and ECG (Table 1),⁵ and subsequent care is based on the estimated degree of risk.

Troponin revolutionized the diagnosis and risk stratification of chest pain. The ACC/AHA guidelines call for measuring biomarkers—preferably troponin—in all patients who present with chest discomfort consistent with an acute coronary syndrome.^4,6

Cardiac troponins I and T have been the biomarkers of choice for detecting myocardial injury,^4,6 since elevated concentrations are highly sensitive and tissue-specific.⁷ Moreover, they identify patients at short-term and long-term risk of cardiac events.^4,8

The introduction of troponin testing led to a substantial increase in the rate of diagnosis of myocardial infarction (MI), with an increase in cardiac care unit admissions of more than 20%.^9,10 This was partly because troponin is released into the blood with even minute myocardial damage, so that some patients who previously would have been diagnosed with unstable angina are now found to have non-ST-segment-elevation MI.¹⁰ However, the increase in admissions may also represent an increase in misdiagnoses, with many clinicians equating an elevated troponin level with acute MI.¹¹

Although an elevated troponin level is 100% specific for myocardial injury, it is not synonymous with MI.¹² Myocardial injury can be caused by a cardiac condition such as tachyarrhythmia, cardiac trauma, congestive heart failure, ventricular hypertrophy, myocarditis, or pericarditis, or by a noncardiac condition such as sepsis, respiratory failure, pulmonary embolism, pulmonary hypertension, cancer chemotherapy, or renal insufficiency.^4,13 Therefore, to avoid a misdiagnosis of MI, the troponin level must be considered in the clinical context.

In fact, Alcalai et al¹¹ noted that almost half of patients with elevated troponin did not really have an acute coronary syndrome. More importantly, in-hospital and long-term survival rates were significantly better for patients with an acute coronary syndrome than for those without, illustrating the importance of identifying and treating the true disease instead of mislabeling the problem as MI.

Bayesian theory predicts that patients with chest pain who have elevated troponin are less likely to truly have an acute coronary syndrome if the rest of their clinical presentation indicates a low probability for heart disease.¹⁴ Indeed, when McDonald et al¹⁵ used a risk-scoring index based on sex, a history of heart failure or coronary artery disease, the ECG, and use of aspirin, the positive predictive value of an abnormal troponin level was 83% at a risk score of 4 or greater, 63% at a score of 3, 52% at a score of 2, 32% at a score of 1, and 29% at a score of 0.

Thus, cardiac biomarkers are not a substitute for traditional clinical assessment, but rather should be used “in conjunction with the clinical history, physical examination, and interpretation of the ECG.”⁶ Consequently, diagnostic protocols that incorporate pretest clinical features to identify low-risk patients have a higher negative predictive value.

This was illustrated in a study by Than et al¹⁶ that aimed to prospectively validate the safety of an accelerated diagnostic protocol to assess chest pain suggestive of an acute coronary syndrome. The protocol included a structured pretest probability scoring method (ie, the Thrombolysis in Myocardial Infarction [TIMI] score), ECG, and a point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The protocol had a negative predictive value of 99.1%, whereas the use of biomarkers alone had a value of 96.1%.

HISTORY AND PHYSICAL EXAMINATION PROVIDE KEY INFORMATION

In a review, Heidenreich et al⁸ noted certain demographic characteristics associated with worse outcomes—ie, older age and male sex; a history of medical conditions such as diabetes, MI, and hypertension; and heart failure on presentation.

A careful assessment of chest pain and associated symptoms helps narrow the differential diagnosis. Features that increase the likelihood of a cardiac origin of chest pain are:

• Chest pain at the time of presentation (likelihood ratio [LR] = 2.0)
• Radiation of the pain to the right shoulder (LR = 2.9), the left arm (LR = 2.3), or both arms (LR = 7.1)
• Nausea or vomiting (LR = 1.9)
• Diaphoresis (LR = 2.0).¹⁷

The physical examination can detect highrisk features such as new murmurs, hypotension, diaphoresis, pulmonary edema, and rales. It is more specific than sensitive and is useful in identifying low-risk patients by targeting potential noncardiac causes of the patient’s symptoms.¹⁸

The efficacy of clinical assessment was studied in 2,271 patients with chest pain presenting to the emergency department.¹⁹ In this cohort, a low-risk group with a 30-day major cardiovascular event rate (death, MI, stroke, or revascularization) of 2.5% could be identified through the use of the US Agency for Health Care Policy and Research criteria.

Electrocardiography

ECG provides important diagnostic and prognostic information and independently predicts death or MI, even after adjustment for cardiac biomarker measurements,^20,21 making it pivotal in the evaluation.⁴ The key features on ECG that increase the probability of MI are:

• New ST-segment elevation (LR 5.7–53.9)
• New Q waves (LR 5.3–24.8).¹⁷

One study²⁰ found that while the troponin T level was a powerful independent marker in patients presenting with MI, its value for risk stratification was enhanced when it was combined with a standard measure such as ECG.²⁰ While more than 90% of patients with STsegment elevation had an adverse outcome, only 31.7% of those patients had an elevated troponin T level.

No component is sufficient by itself

Thus, in spite of the proliferation of cardiac diagnostic tests, the initial bedside assessment of chest pain remains paramount. In fact, in patients presenting to the emergency department with chest pain, low risk (ie, those with a < 5% probability of MI) may be identified by presenting symptoms, medical history, and ECG alone.¹⁹

Furthermore, although clinical assessment, ECG, and cardiac biomarker testing each provide incremental benefit in assessing chest pain, no component is sufficient by itself. Sanchis et al²² found that even in patients with a normal troponin I level, the risk remained high in the case of ST-segment depression, and that even without signs of ischemia, the probability of cardiac events was 16% when the chest pain score was 11 points or higher.²² Consequently, a normal troponin level, ECG, or any other predictor alone would not ensure a good prognosis.

BIOMARKERS INSTEAD OF STRESS TESTING?

The ACC/AHA guidelines for the diagnosis of patients with unstable angina and non-STsegment elevation MI say that stable patients at low risk with no evidence of ischemia on initial assessment can be admitted to a chest pain unit for observation with serial cardiac biomarkers and ECG.⁴ At the end of the observation period, those who have reassuring results on ECG and normal cardiac biomarker measurements undergo functional cardiac testing or stress testing, or both.⁴

Exercise treadmill testing is a cornerstone of confirmatory testing in an accelerated diagnostic protocol because it is readily available, safe, and easy to do.¹⁸ A low-risk result was shown to have a high negative predictive value,^23,24 so that the likelihood of an acute coronary syndrome is low enough for safe discharge.

However, the overall process is not ideal since it is time-consuming, generates additional costs, and can have false-positive results in patients who are otherwise deemed not to be at high risk. While some studies provided an optimistic view about discharging low-risk patients with negative biomarkers without stress testing,^7,25 others have discouraged omitting exercise treadmill testing from protocols.^22,26

Others have proposed combining a biomarker with an imaging study such as coronary computed tomographic (CT) angiography.²⁷ Normal findings on this study have been shown to have a negative predictive value of up to 100% for ruling out an acute coronary syndrome and the occurrence of major adverse cardiovascular events in the long term.^28,29 Furthermore, it allows more-inclusive assessments of chest pain and can exclude other life-threatening causes such as pulmonary embolism and aortic dissection (referred to as the “triple rule-out”).³⁰

However, 25% to 50% of patients presenting to the emergency department with chest pain may not be candidates for CT angiography because of obesity, contrast allergy, intolerance to beta-blockade, arrhythmia, renal insufficiency, or a history of coronary artery disease.¹⁸ Moreover, it may be more efficient and less costly to discharge some patients without coronary CT angiography³¹ with the help of novel biomarkers without routine additional testing. This may spare patients the additional radiation exposure from CT angiography or nuclear imaging.^27,32

New biomarkers may, it is hoped, better distinguish patients at low risk from those at high risk without resorting to stress testing. Several of these markers are moving toward mainstream clinical use. For a biomarker to be prognostically equivalent to stress testing, it must be able to tell us if the likelihood of an acute coronary syndrome is low enough for safe discharge—ie, it must have a significantly high negative predictive value. Also, it must be an independent predictor of adverse outcomes, particularly in patients deemed at low risk by initial low troponin measurements. Biomarkers that have shown promise in this regard include high-sensitivity troponin, brain-type natriuretic peptide (BNP), cystatin C, and ischemia-modified albumin.

HIGH-SENSITIVITY CARDIAC TROPONIN ASSAYS

Although we speak of “high-sensitivity troponin,” these new assays detect the same molecule as do traditional troponin assays. The difference is that high-sensitivity assays can detect and measure troponin at concentrations much lower than the traditional assays can. In fact, high-sensitivity troponin assays can detect and measure troponin at very low levels in almost all healthy people.

Studies have shown that the high-sensitivity assays have better analytical accuracy and sensitivity than older assays.¹²

Aldous et al³³ reported that, in patients who presented to the emergency department within 4 hours of the onset of chest pain, an elevation in troponin T on a high-sensitivity assay had a positive predictive value of 53.8% and a negative predictive value of 98.3%.

Weber et al³⁴ found the diagnostic value of the high-sensitivity troponin T assay to be superior to that of a contemporary troponin T assay (area under the receiver-operating-characteristics curve [AUC] of 0.949 vs 0.929). Even when the contemporary troponin T assay was negative, the high-sensitivity assay provided strong diagnostic information (AUC 0.81). Furthermore, the high-sensitivity assay provided superior independent prognostic power for death within 6 months.

Hochholzer et al³⁵ reported a prognostic accuracy for death significantly higher (AUC 0.79) than that of contemporary troponin T (AUC 0.69). A concentration of high-sensitivity troponin T above 14 ng/L improved the prediction of death (hazard ratio 2.60) but not of subsequent acute MI in patients with acute chest pain. Therefore, a negative high-sensitivity troponin T assay identifies patients with a good prognosis and who may be discharged without further testing if their clinical presentation and ECG are also reassuring.

Keller et al³⁶ compared the diagnostic performance of the high-sensitivity cardiac troponin I assay against 11 other biomarkers, including a contemporary cardiac troponin I assay. The contemporary troponin I and the high-sensitivity troponin I assays performed best. The high-sensitivity troponin I assay at admission had a sensitivity of 82.3% and a negative predictive value of 94.7% for ruling out acute MI, whereas the contemporary troponin I assay had a sensitivity of 79.4% and a negative predictive value of 94.0%.

Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both troponin I assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value for ruling in acute MI for high-sensitivity cardiac troponin I increased from 75.1% at admission to 95.8% after 3 hours; for the contemporary assay, it increased from 80.9% at admission to 96.1%.³⁶

The authors concluded that performing either of the cardiac troponin I assays 3 hours after admission may help in ruling out MI early on, with a negative predictive value greater than 99%. Moreover, the relative change in concentration within the 3 hours after admission, combined with the 99th percentile diagnostic cutoff value on admission, improves specificity, allowing acute MI to be accurately ruled in.³⁶

Of note, though studies have confirmed that a measurement at 3 hours identifies most cases of MI early, they have not used the recommended maximal sensitivity interval for troponin measurements (6 hours or more).⁶

A proposed algorithm for diagnosing acute MI with a high-sensitivity assay

While high-sensitivity troponin T assays can improve the early diagnosis of acute MI, how best to use them is yet to be defined. They still lack specificity for acute coronary syndromes, with positive predictive values as low as 50%.³⁷

Reichlin et al³⁸ developed and validated an algorithm for rapidly ruling out or ruling in acute MI using a high-sensitivity cardiac troponin T assay, incorporating baseline values and absolute changes within the first hour. Using a baseline threshold of 12 ng/L or less and an absolute change of 3 ng/L or less, they found a sensitivity and negative predictive value of 100%, making these good criteria for ruling out acute MI.

Using a baseline threshold of 60 ng/L or greater and a change from baseline to 1 hour of at least 15 ng/L, the specificity was 97% and the positive predictive value was 84%, making these good criteria for ruling in acute MI.

Patients whose values were in between were classified as being in an “observationalzone group,” in which the prevalence of acute MI was 8%. The cumulative 30-day survival rate was 99.8% in patients in whom the test ruled out MI, 98.6% in the observational-zone patients, and 95.3% in patients in whom the test ruled in MI.³⁸ Using this simple algorithm allowed a safe rule-out as well as an accurate rule-in of acute MI within 1 hour in 77% of unselected patients with acute chest pain; thus, it may obviate the need for prolonged monitoring and serial measurements in three out of four patients.”

Newby³⁹ stated that such an algorithmic approach must be validated in a prospective study that assesses not only sensitivity, negative predictive value, specificity, and positive predictive value, but also the implications for clinical outcomes and the cost of widespread implementation.

In the meantime, clinicians must keep in mind that patient populations in clinical practice are less selected, the prevalence of MI may broadly vary, and confounding comorbidities such as heart failure and renal insufficiency are more common. Studies are also needed to verify whether other factors such as age, sex, and time from symptom onset should be considered.

BRAIN-TYPE NATRIURETIC PEPTIDE

BNP is a 32-amino-acid natriuretic peptide that is released from myocytes. The amount released depends on wall stress brought on by heart failure, ischemic heart disease, or other conditions.

In a study of the diagnostic utility of BNP in the workup of acute chest pain, Haaf et al⁴⁰ found that BNP levels at presentation were significantly higher in patients with acute MI than in patients with other diagnoses. However, the diagnostic accuracy of BNP was lower than that of cardiac troponin T at presentation, though its independent predictive value for all-cause mortality was more accurate than that of troponin T.

Elevation of the BNP ⁴¹ or the N-terminal pro-BNP ^42,43 level was shown to also provide unique prognostic information in patients with suspected and confirmed acute coronary syndrome and was associated with higher rates of short-term and long-term mortality. Therefore, BNP appears useful for the prognosis but not the diagnosis of acute coronary syndromes.

CYSTATIN C

The protein cystatin C, widely used as a biomarker for kidney disease, has more recently been touted as a prognostic marker in acute coronary syndromes.

Jernberg et al⁴⁴ reported that, in patients with a suspected or confirmed acute coronary syndrome, a single measurement of cystatin C significantly improved the early stratification of risk.⁴⁴ Specifically, the cystatin C level was independently associated with mortality risk but not with the risk of subsequent MI.

In another study,⁴⁵ the cystatin C concentration independently predicted the risk of cardiovascular death or MI in non-ST-segment elevation acute coronary syndrome. However, the additive predictive value of cystatin C in these patients was found to be small when clinical risk factors and biomarkers of MI were used in the prediction model. Therefore, cystatin C may predict global risk but does not appear to be useful in diagnosing MI.

ISCHEMIA-MODIFIED ALBUMIN

A major limitation of troponin is that it cannot detect reversible myocardial ischemia in the absence of cardiac necrosis, making stress testing necessary to unmask potential reversible ischemia.

Ischemia-modified albumin has been proposed as a means of detecting cardiac ischemia even if necrosis is absent. It is a product of the N-terminus alteration of albumin caused by myocardial ischemia, which reduces the ability of cobalt to bind to albumin and can be detected with the albumin cobalt binding test. This marker might have a high negative predictive value, ruling out acute coronary syndromes in conditions of low pretest probability with negative necrosis markers and ECG.^13,46

Although ischemia-modified albumin does show promise, doubt remains as to its validity as a biomarker, as its mechanism of generation is not known. Some have suggested that it is in fact a marker of oxidative stress.⁴⁷

PANELS OF MARKERS

The individual biomarkers we have discussed here have advantages and limitations in the emergency workup of chest pain. The concept of using a multimarker panel has been raised as a way of amplifying the positive attributes of individual biomarkers and compensating for their shortcomings.

Sabatine et al⁴⁸ tested this approach in patients with acute coronary syndromes who were at high risk of an adverse outcome. When patients were categorized at presentation on the basis of the number of elevated biomarkers such as cardiac troponin I, C-reactive protein, and BNP, the risk of death nearly doubled with each additional biomarker that was elevated.

The relationship was similar for the end points of MI, heart failure, and the composite at 30 days and 10 months. In a cohort of 1,635 patients, the number of elevated biomarkers remained a predictor of the composite end point after adjustment for known clinical predictors. The risk of death, MI, or heart failure by 6 months was 2.1 times higher in patients with one elevated biomarker, 3.1 times higher in those with two, and 3.7 times higher in those with three.

The authors concluded that a multimarker strategy that categorizes patients on the basis of the number of elevated biomarkers at presentation allows risk-stratification of short- and long-term cardiac events.

Tello-Montoliu et al⁴⁹ tested this idea in patients with non-ST-segment elevation acute coronary syndromes using a panel consisting of cardiac troponin T, C-reactive protein, N-terminal pro-BNP, and fibrin D-dimer. The risk of a major event (death, new acute coronary syndrome, revascularization, or heart failure) at 6 months was associated with abnormal biomarker levels, especially with the presence of three positive biomarkers, even after adjustment for clinical characteristics and ECG findings.

van der Zee et al⁴³ showed that a positive biomarker panel consisting of C-reactive protein and N-terminal pro-BNP identified patients with chest pain and a normal or nondiagnostic ECG who have a high long-term risk of cardiovascular death.

Glaser et al⁵⁰ evaluated the combination of cardiac troponin I, BNP, homocysteine, C-reactive protein, placental growth factor, myeloperoxidase, choline, soluble CD40 ligand, ischemia-modified albumin, and lipoprotein-associated phospholipase A2 in patients with a suspected acute coronary syndrome. The combination of BNP, placental growth factor, and estimated glomerular filtration rate was the most accurate predictor of major adverse cardiovascular events compared with any other biomarker or clinical factor. With appropriate cutoff values, the negative predictive value for a major adverse cardiovascular event at 1 year was as high as 99.1%.

This study highlighted the importance of combining biomarkers, showing that with a negative predictive value of 97% for 30-day events, the combination of placental growth factor, BNP, and cardiac troponin I may help surmount the delay from symptom onset to cardiac troponin increase, thus permitting a more timely diagnosis and safe discharge within 12 hours.

Comment. These studies raise the promise that panels of biomarkers can be used in patients deemed to be at low risk after clinical assessment and troponin evaluation to enable them to be safely discharged early and to obviate the need for stress testing.

If we assume that unstable cardiac disease requiring hospitalization accounts for 35% of patients with chest pain, a hypothetical panel of biomarkers with a sensitivity and specificity of 95% for adverse cardiac outcomes would have a positive predictive value of 91% and a negative predictive value of 97%. The negative likelihood ratio of this hypothetical biomarker panel would be 0.05, while the positive likelihood ratio would be 19. This performance level means that in patients with a pretest probability less than 50%, the posttest probability can be reduced to below 10%, so that such patients can be safely discharged without further hospital evaluation.

Conversely, a positive test result in patients with pretest probability of 30% or greater raises the posttest probability to nearly 90%, meaning that such patients should be considered for aggressive intervention without the need for stress testing.

RETURN TO OUR SCENARIOS

Chest pain remains a nonspecific complaint, and the interpretation of biomarkers to find the cause presents clinicians with challenges, as illustrated by the cases introduced at the beginning of this article.

The cardiac troponin I elevation in scenario 1 led to an initial diagnosis of unstable angina. However, coronary angiography showed lesion-free coronary arteries, thus excluding ischemic heart disease. When other diseases that could cause elevated cardiac troponin I were considered and investigated with further diagnostic tests such as D-dimer, pulmonary embolism became the new working diagnosis, and this was confirmed by CT angiography.

Similarly, given the laboratory values for the patient in scenario 2, the condition could have been mistaken for an acute coronary syndrome. However, the absence of evidence on ECG to support this diagnosis would indicate an erroneously elevated biomarker secondary to his background of chronic renal insufficiency.

Although long considered a disease of elderly men, cardiovascular disease is increasingly recognized for its impact on women. In fact, it is now the leading cause of death in women worldwide, and in the United States more women than men die of it.¹

Given this epidemic of cardiovascular disease in women, more research is now being dedicated to identifying sex-specific aspects of cardiovascular disease, the better to prevent and treat it.

This review will focus on the most recent information about how prevention, symptoms, and underlying cardiovascular conditions differ in women.

PRIMARY PREVENTION: ONGOING DEBATE

Women who diet, exercise, and abstain from smoking have an 80% lower rate of cardiovascular events than the female population overall.² However, beyond lifestyle modification and blood pressure control, there is ongoing debate as to the efficacy of our available therapies for preventing cardiovascular disease in women.

Aspirin for primary prevention in women: No benefit?

The use of aspirin to prevent cardiovascular disease in women has long been controversial. Several trials showed a lower rate of myocardial infarction in people using aspirin for primary prevention, but most of the patients in the initial trials were men (Table 1).³

The Women’s Health Study⁴ assigned 39,876 women age 45 and older to receive either aspirin (100 mg on alternate days) or placebo, and monitored them for more than 10 years for major cardiovascular events (non-fatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes).

The results, published in 2005, showed that the rates of myocardial infarction and cardiovascular death were not significantly lower in the aspirin group, although the rate of ischemic stroke was 24% lower. There were more hemorrhagic strokes in the aspirin group (not statistically significant), and there was significantly more gastrointestinal bleeding. The study showed the relative risk (RR) and 95% confidence interval (CI) for several outcomes in aspirin users were:

• Myocardial infarction—RR 1.02, 95% CI 0.84–1.25, P = .83
• Cardiovascular death—RR 0.95, 95% CI 0.74–1.22, P = .68
• Ischemic stroke—RR 0.76, 95% CI 0.63–0.93, P = .009
• Hemorrhagic stroke—RR 1.24, 95% CI 0.82–1.87, P = .31
• Gastrointestinal bleeding—RR 1.4, 95% CI 1.07–1.83, P = .02.

A later analysis indicated that noncompliance had no effect on these results.⁵

However, a subgroup analysis of women over age 65 found a significant reduction in the rate of myocardial infarction and in the composite end point of myocardial infarction, stroke, and cardiovascular death, although there was a trend toward a higher rate of gastrointestinal bleeding. The numbers in aspirin users in the subgroup over age 65 were as follows:

• Myocardial infarction—RR 0.66, 95% CI 0.44–0.97, P = .04
• Composite end point—RR 0.74, 95% CI 0.59–0.92, P = .008.

Aspirin was taken every other day and at a higher dose than the 81 mg recommended in the United States, although it is unclear how these differences may have affected the results.

United States Preventive Services Task Force (USPSTF) recommendations. Although the USPSTF currently recommends aspirin for men age 45 to 79 to prevent myocardial infarction, it offers no such recommendation for women, largely because of the results of the Women’s Health Initiative study. However, it does recommend aspirin to prevent ischemic stroke in women age 55 to 79.³ Additionally, aspirin can be considered for prevention of myocardial infarction in women who are over age 65 or at high risk.⁶

This is based on Women’s Health Study data for women over age 65 showing a number needed to treat of 47 to prevent 1 cardiovascular event, whereas the number needed to harm, defined by a major hemorrhagic event, was 128. In contrast, in women younger than age 65, the number needed to treat was 2,001 and the number needed to harm was 196.⁴

High-risk features, as defined by the guidelines, are a history of coronary artery disease, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes, or chronic kidney disease, or a 10-year predicted risk of cardiovascular disease of more than 10%.

Jardine et al⁷ reported that aspirin was beneficial in patients with chronic kidney disease. The rates of cardiovascular death, death from any cause, and stroke were significantly lower in patients with a glomerular filtration rate (GFR) less than 45 mL/min if they received aspirin. The rates were also lower in aspirin recipients with a GFR between 46 and 60 mL/min, but the difference was not statistically significant.

Comments. Given the risk of significant gastrointestinal bleeding and a trend toward hemorrhagic stroke with aspirin use,⁴ it is important to weigh the risks and benefits of aspirin for primary prevention in women.

Our understanding of the reasons for sex differences in the clinical benefits of aspirin for primary prevention is limited at this point. Studies have shown a higher prevalence of platelet reactivity and aspirin resistance in women than in men, suggesting that hormonal differences may play a role.⁸ There has been mention of using higher doses of aspirin in women to achieve the same level of platelet inhibition as in men. However, studies have shown essentially equal platelet inhibition in both men and women after aspirin administration.⁹ Therefore, more work needs to be done to better understand the observed sex differences in response to aspirin.

Given suggestions that statins may not be effective in women¹⁰ and the fact that women were underrepresented in earlier statin trials, a number of studies have examined this issue in the last several years.

The JUPITER trial (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin)¹⁰ enrolled patients who had no history of coronary artery disease and who had a C-reactive protein level equal to or greater than 2 mg/L and a low-density lipoprotein cholesterol level of less than 130 mg/dL. (Of note, these patients would not have met the criteria for receiving a statin for primary prevention according to the current Adult Treatment Panel guidelines.)

The women in the trial who received rosuvastatin had a 46% lower incidence of myocardial infarction, stroke, revascularization, hospitalization for unstable angina, or death from cardiovascular causes. In addition, a meta-analysis performed by the authors showed a one-third reduction of cardiovascular disease end points in women. However, there was no reduction in the mortality rate.

Reprinted from Kostis WJ, et al. Meta-analysis of statin effects in women versus men. J Am Coll Cardiol 2012; 59:572–582, with permission from Elsevier.

Other statin trials. A later meta-analysis of randomized primary prevention trials found that men and women derived similar benefit from statins in terms of cardiovascular disease end points and all-cause mortality (Figure 1),¹¹ although five of the trials included a small number of secondary prevention patients. In contrast, a meta-analysis of only primary prevention patients showed no benefit of statin therapy in all-cause mortality, although the authors acknowledged that there were insufficient data to look specifically at women in this sample.¹²

A Cochrane review conducted before the JUPITER data were available concluded that there was insufficient evidence to prescribe statins for primary prevention in patients at low cardiovascular risk.13 However, an updated version that included results of the JUPITER trial concluded that there was a reduction in the rate of all-cause mortality and cardiovascular events in both men and women receiving a statin for primary prevention.14

Given these conflicting results, debate continues as to the benefit of statins for primary prevention, not only in women but in the population as a whole.^15,16 The definition of high risk, in terms of comorbidities and lipid profile, also continues to evolve and will likely be an important factor in identifying women who will benefit from statin therapy for primary prevention.

Statin adverse effects. Much of the debate about statins for primary prevention stems from concern about the adverse effects of these drugs. In addition to myopathy, there have been reports of increased risks of new diabetes and cognitive impairment.¹⁶ In a post hoc analysis of the Women’s Health Initiative, the adjusted risk of diabetes was 48% higher in women taking a statin for primary prevention than in similar women not taking a statin.¹⁷ (This finding should be viewed with caution, since the data are observational.)

There has also been a question of whether women experience more side effects from statin therapy than men do. Although thin or frail women over age 80 are more susceptible to statin side effects, this finding has not been observed in younger women.¹⁸

Comment. In view of the data, it appears reasonable to consider statin therapy for primary prevention in women deemed to be at high risk based on the current guidelines. However, as always, one must consider whether the benefits outweigh the risks for the individual patient. More study is needed to better evaluate the utility of statin therapy in primary prevention.

Hormone therapy

Hormone therapy has received enormous attention in both the medical community and the public media. (Hormone therapy is either combined estrogen and progestin or estrogen alone, used to treat symptoms of menopause and to prevent osteoporosis in postmenopausal women. Here, we will discuss hormone therapy and not hormone replacement therapy, which is used specifically to treat premature menopause.)

The safety of estrogen-progestin combination therapy has been the subject of great debate since a Women’s Health Initiative study showed a trend toward a greater risk of cardiovascular disease in estrogen-progestin users.¹⁹

Women who received estrogen by itself showed no difference in cardiovascular risk compared with those who received placebo. Unopposed estrogen is rarely prescribed, since it increases the risk of endometrial cancer in women who have not undergone hysterectomy.²⁰

Both unopposed estrogen and combination therapy have also been found to increase the risk of stroke,²⁰ deep vein thrombosis, gallbladder disease, and certain forms of urinary incontinence.

Guidelines on hormone therapy. The USPSTF does not recommend hormone therapy to prevent chronic conditions, basing its decision on the findings from the Women’s Health Initiative.²¹ The American College of Cardiology and American Heart Association (ACC/AHA) 2007 guidelines advise against continuing hormone therapy in patients who present with acute coronary syndrome, although recommendations need to address a broader scope of primary and secondary prevention patients.

Does timing matter? There is a hypothesis that when hormone therapy is started may affect the cardiovascular risk. A secondary analysis of the Women’s Health Initiative study²² showed a trend towards less cardiovascular disease in women who started hormone therapy within 9 years of menopause, whereas those starting it later had a statistically significantly higher rate of cardiovascular mortality. However, all women had a higher risk of stroke while on hormone therapy, regardless of timing.²²

A study of 1,006 healthy women age 45 to 58 whose last menstrual period was 3 to 24 months before enrollment found a statistically significant reduction in the composite end point of death, hospital admission for myocardial infarction, or heart failure with hormone therapy.²³ There was no significant increase in breast cancer, deep vein thrombosis, or stroke after 10 years of randomized treatment.

A retrospective analysis of 71,237 postmenopausal women in the California Teachers Study also found a significant reduction in the rate of cardiovascular disease-related deaths with hormone therapy in younger women (ie, younger than age 65), but not in older women.²⁴ The authors concluded that it may not just be the years after menopause but also the baseline age of the woman that may influence outcomes.

In view of these studies, there is increasing recognition that hormone therapy may, in fact, still be beneficial in terms of cardiovascular and all-cause mortality in carefully selected patients. The cardiovascular risk in women, specifically older women who have had a longer duration of menopause, should also be weighed against the potential benefits of therapy in terms of quality of life and symptom relief.

Trials under way include the Kronos Early Estrogen Prevention (KEEP) and Danish Osteoporosis Prevention (DOPS) studies. KEEP is a 4-year, double-blind, randomized controlled trial of hormone therapy in women within 3 years of menopause. DOPS is an open-label trial that includes more than 1,000 women with early menopause. The results of these trials will likely affect future recommendations.

WOMEN’S SYMPTOMS: TYPICAL OR ATYPICAL?

Whether the presenting symptoms of acute coronary syndromes differ between men and women has been much debated.

More women than men seem to present with atypical symptoms.^25–27 (The term “atypical” refers to symptoms that do not include the three classic components of angina: substernal chest pain or discomfort, provoked by exertion or emotional stress, and relieved by rest or nitroglycerin, or both.²⁸)

However, most women still present with chest pain. In a study by Dey et al,²⁶ 92% of the 7,638 women with presumed acute coronary syndrome presented with chest pain. In women who had atypical symptoms, dyspnea, nausea, vomiting, and diaphoresis were the most common symptoms. Women were significantly more likely than men to present with nausea and vomiting (32% vs 23%, P = .001).

Women in the study were also more likely to have angiographically normal coronary arteries (12% vs 6%, P < .001).²⁶ This difference may be largely due to noncardiac chest pain, but it may also represent conditions such as vasospasm, microvascular disease, or stress cardiomyopathy, all of which disproportionately affect women.

An earlier review of 10 major studies found a higher percentage of women presenting with atypical symptoms (37.5% of women vs 27.4% of men).²⁵ However, symptoms were not a focus of these studies, and the findings may therefore be skewed by inaccurate documentation.

Atypical warning signs. Although most women with acute coronary syndrome present acutely with chest pain, women may have different warning signs than men. Only about one-third of women experience angina before presentation.²⁹ Compared with men, women are more likely to complain of shortness of breath, fatigue, and weakness leading up to a diagnosis of a myocardial infarction.²⁹ Therefore, the prodromal symptoms of cardiovascular disease may in fact be significantly more atypical in women than in men, suggesting the need for heightened vigilance in the cardiovascular evaluation of women who have nonanginal symptoms.

THE ROLE OF STRESS TESTING IN WOMEN

Stress testing in various forms continues to be widely used in the diagnosis of heart disease in women, although data are scarce regarding its utility in women.

The ACC/AHA guidelines continue to recommend exercise stress electrocardiography (ECG) for women who have symptoms, are at intermediate risk, and have a normal result on resting ECG.³⁰

Exercise ECG has a higher false-positive rate in women than in men,³¹ and there appears to be no relationship between exercise-induced ST-segment depression and the rate of cardiovascular mortality or all-cause mortality in women.^32,33 On the other hand, exercise ECG yields valuable additional information such as exercise capacity, chronotropic response, heart-rate recovery, and blood pressure response, all of which have important diagnostic and prognostic implications in women.³⁴

For those who have an abnormal resting ECG, the addition of an imaging test, ie, echocardiography or single-photon emission computed tomography (SPECT), is indicated. Both have limitations: SPECT can give false-positive results because of breast attenuation, and echocardiography varies in accuracy depending on the quality of acoustic windows obtained. Both exercise stress SPECT and exercise stress ECG have higher sensitivity and specificity than electrocardiographic exercise stress testing alone,³⁴ and there is evidence that the two imaging tests are comparable in women.³⁵

In those women who have baseline left bundle branch block or who cannot exercise, a pharmacologic stress test should be performed. Of course, this is a less desirable testing method, given the loss of valuable information obtained from exercising the patient.

UNDERLYING CONDITIONS THAT DISPROPORTIONATELY AFFECT WOMEN

Microvascular angina

Perimenopausal and postmenopausal women account for 70% of patients presenting with chest pain and elevated cardiac enzymes but no significant angiographic evidence of coronary artery disease.³⁶ This condition, commonly called syndrome X, is often characterized by lingering, dull chest pain after exertion and is seen more frequently in women younger than those presenting with classic cardiovascular disease.

Because at least some of these patients show evidence of ST-segment depression and reversible perfusion defects on imaging, the condition is thought to be caused by ischemia of the microvascular bed leading to microvascular angina.³⁷

Although this is still an area of research, microvascular dysfunction has recently been proposed as an explanation for these findings. Abnormal vasoconstriction and impaired vasodilation of the microvascular bed, insulin resistance, increased systemic inflammation, and abnormal pain response have all been cited as potentially contributing to microvascular dysfunction.³⁶

Estrogen deficiency is thought to play a central role in the significantly increased burden of microvascular dysfunction seen in women, with some studies suggesting that hormone therapy can relieve symptoms. However, given the concerns about adverse cardiovascular outcomes in women on hormone therapy, there has been little investigation of this treatment for this disorder.

Studies have shown worse cardiovascular outcomes and higher rates of angina-related hospitalization and repeat heart catheterizations in women with microvascular dysfunction.³⁸

Diagnosing microvascular angina must be done indirectly, as there is no safe and minimally invasive technique by which to directly observe the microvasculature. Current coronary angiographic techniques cannot image vessels smaller than 0.5 mm in diameter, and endomyocardial biopsy cannot access the larger periarterioles thought to play a major role in regulating coronary blood flow.³⁹

Image courtesy of Dr. Deborah Kwon

Because the coronary microvasculature controls total coronary resistance and therefore regulates myocardial blood flow, measuring myocardial blood flow at maximum vasodilation, termed coronary flow reserve, can indirectly evaluate the degree of microvascular dysfunction.⁴⁰ In the absence of obstructive epicardial coronary disease, noninvasive imaging techniques or provocative testing in the coronary catheterization lab can be used for this purpose. In terms of noninvasive imaging, perfusion magnetic resonance imaging (Figure 2) or positron emission tomography is often performed.⁴⁰

Coronary flow reserve can also be measured by invasive means in the catheterization laboratory after maximum hyperemia is induced by adenosine or other such vasodilatory agents.⁴¹ However, measurements obtained in this invasive manner are greatly affected by hemodynamic changes and can have poor reproducibility.⁴⁰

Proposed therapy for microvascular angina. Once a diagnosis has been made, lifestyle modification, antianginal agents, angiotensin-converting enzyme inhibitors, and statins have been suggested for therapy.³⁹ Pain management techniques are also used, given the increased pain sensitivity observed in women with this condition. However, no therapy to date has proven overwhelmingly effective in these patients, and a disproportionate number of women suffer from chronic symptoms despite these treatments. Currently, researchers are looking for new agents to treat microvascular disease.

Stress cardiomyopathy

Images courtesy of Dr. Michael Faulx and Dr. Shikhar Agarwal

Stress cardiomyopathy, also called takotsubo cardiomyopathy or “broken heart syndrome,” is another condition that disproportionately affects postmenopausal women. It is often associated with sudden emotional or physical stress. Patients present with signs and symptoms of myocardial infarction without demonstrable epicardial coronary artery disease. The hallmark of stress cardiomyopathy is left ventricular dysfunction, often severe, with classic apical ballooning that resembles a Japanese fishing pot (takotsubo) used to trap octopuses, hence the name (Figure 3).

According to a review by Akashi et al⁴² based on previously reported Mayo Clinic criteria, the diagnosis of stress cardiomyopathy includes each of the following:

• Transient hypokinesis, akinesis, or dyskinesis in the left ventricular midsegments with or without apical involvement; regional wall-motion abnormalities that extend beyond a single epicardial vascular distribution; and frequently, but not always, a stressful trigger
• Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture
• New abnormality on ECG (eg, ST-segment elevation, T-wave inversion) or modest elevation in cardiac troponin
• Absence of pheochromocytoma or myocarditis.

From 80% to 100% of reported cases are in women, with an average age range of 61 to 76.⁴² It is unclear why there is such an overwhelming postmenopausal female preponderance of the disease. Studies have implicated estrogen deficiency, as it appears to attenuate the levels of cardioprotective substances in the body that in part regulate catecholamine surges and may also increase the level of oxidative stress.⁴²

Several mechanisms for this condition have been proposed. The condition may be caused by multivessel epicardial coronary spasm or spontaneously resolved plaque rupture, resulting in stunned myocardium. However, the regional distribution of wall-motion abnormality is often out of proportion to the level of cardiac enzyme elevation, and in the case of plaque rupture, is frequently not consistent with a single coronary vessel.⁴² A catecholamine surge causing myocardial and neurogenic stunning has also been proposed, although many of these patients have normal catecholamine levels.⁴² Finally, microvascular dysfunction has been found in a number of patients with this condition. However, it is difficult to establish a causal relationship, since apical ballooning could result in microvascular dysfunction.⁴²

Treatment of stress cardiomyopathy has not been standardized, in part because the left ventricular dysfunction often resolves spontaneously within several weeks.^43,44 Given the proposed catecholaminergic mechanism, some experts believe that beta-blockers are contraindicated because of the resulting unopposed activation of alpha-adrenoreceptors. However, this continues to be a matter of debate. There is also no clear indication for other standard therapies for acute coronary syndrome such as aspirin and heparin, and their use appears to vary in clinical practice.

Although most patients improve with time and recurrence is exceedingly rare, it should be emphasized that they may present acutely with severe hemodynamic instability and cardiogenic shock. Therefore, advanced means of support, such as an intra-aortic balloon pump, may be indicated until the patient recovers from the acute phase of the disease.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome resulting from dissection of the coronary intimal or medial layer and associated hematoma formation, leading to coronary occlusion.^45,46 In a case series of 87 patients, 49% presented with an ST-segment elevation myocardial infarction, and 23% were found to have multivessel SCAD.⁴⁶

SCAD occurs predominantly in young, healthy women (mean age 30–45 years). Approximately 70% of cases are in women, 30% of whom are in the peripartum period.⁴⁵ The reasons for the increased risk during pregnancy have not yet been elucidated, but changing sex hormones, increased cardiac output and shear stress, and an increased inflammatory response have been implicated.⁴⁵

Diagnosing SCAD. Coronary angiography should be performed with extreme caution in patients suspected of having SCAD, given the risk of further dissection of the artery with forceful injections. In certain cases, it may be difficult to detect SCAD on routine angiography if there is no communication between the true and false lumen.

If the suspicion for SCAD is high, intravascular ultrasonography or optical coherence tomography can be used to better evaluate the vessel.⁴⁵ Although optical coherence tomography has greater spatial resolution, it is more costly and is not as widely used as intravascular ultrasonography in the clinical setting

Managing SCAD. Although conservative management and coronary artery bypass grafting have been shown to cause minimal in-hospital morbidity, percutaneous coronary intervention has been complicated by technical failure in up to 35% of patients in one series.⁴⁶

While there is no standardized way to manage these patients, experts currently recommend conservative management with standard therapies for acute coronary syndrome (Figure 4). Although antithrombotic agents can decrease thrombus burden, they must be used with caution, because they also increase the risk of bleeding into the false lumen.

If patients experience recurrent or ongoing ischemia despite conservative management, then revascularization should be considered. Optical coherence tomography or intravascular ultrasonography is recommended to ensure proper stent alignment and positioning.

Coronary artery bypass grafting could be considered in preference to percutaneous coronary intervention, given that the former appears to be safer,⁴⁶ although this requires further investigation. Some studies have cautioned against using fibrinolytic therapy, based on anecdotal evidence that it may further propagate the dissection,⁴⁵ although this therapy has been used in other case studies.⁴⁶

While mortality rates are relatively low (95% survival at 2 years),⁴⁵ the estimated risk of recurrent SCAD at 10 years is approximately 30%.⁴⁶

Image courtesy of Dr. Heather Gornik

Associated with fibromuscular dysplasia. Of note, a sizeable number of patients with SCAD have been found to have fibromuscular dysplasia. This is a nonatherosclerotic, noninflammatory vascular condition that can affect any vascular bed in the body, although there is a predilection for the renal and carotid arteries (Figure 5).⁴⁷ Fibromuscular dysplasia also disproportionately affects women and appears to be a concomitant condition in the majority of patients with SCAD.⁴⁷ Imaging of the carotid and renal arteries of patients with SCAD has revealed a number of cases of fibromuscular dysplasia.^46,48 This noted association will likely allow for ongoing research to better understand the pathophysiology of these two conditions.

Although long considered a disease of elderly men, cardiovascular disease is increasingly recognized for its impact on women. In fact, it is now the leading cause of death in women worldwide, and in the United States more women than men die of it.¹

Given this epidemic of cardiovascular disease in women, more research is now being dedicated to identifying sex-specific aspects of cardiovascular disease, the better to prevent and treat it.

This review will focus on the most recent information about how prevention, symptoms, and underlying cardiovascular conditions differ in women.

PRIMARY PREVENTION: ONGOING DEBATE

Women who diet, exercise, and abstain from smoking have an 80% lower rate of cardiovascular events than the female population overall.² However, beyond lifestyle modification and blood pressure control, there is ongoing debate as to the efficacy of our available therapies for preventing cardiovascular disease in women.

Aspirin for primary prevention in women: No benefit?

The use of aspirin to prevent cardiovascular disease in women has long been controversial. Several trials showed a lower rate of myocardial infarction in people using aspirin for primary prevention, but most of the patients in the initial trials were men (Table 1).³

The Women’s Health Study⁴ assigned 39,876 women age 45 and older to receive either aspirin (100 mg on alternate days) or placebo, and monitored them for more than 10 years for major cardiovascular events (non-fatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes).

The results, published in 2005, showed that the rates of myocardial infarction and cardiovascular death were not significantly lower in the aspirin group, although the rate of ischemic stroke was 24% lower. There were more hemorrhagic strokes in the aspirin group (not statistically significant), and there was significantly more gastrointestinal bleeding. The study showed the relative risk (RR) and 95% confidence interval (CI) for several outcomes in aspirin users were:

• Myocardial infarction—RR 1.02, 95% CI 0.84–1.25, P = .83
• Cardiovascular death—RR 0.95, 95% CI 0.74–1.22, P = .68
• Ischemic stroke—RR 0.76, 95% CI 0.63–0.93, P = .009
• Hemorrhagic stroke—RR 1.24, 95% CI 0.82–1.87, P = .31
• Gastrointestinal bleeding—RR 1.4, 95% CI 1.07–1.83, P = .02.

A later analysis indicated that noncompliance had no effect on these results.⁵

However, a subgroup analysis of women over age 65 found a significant reduction in the rate of myocardial infarction and in the composite end point of myocardial infarction, stroke, and cardiovascular death, although there was a trend toward a higher rate of gastrointestinal bleeding. The numbers in aspirin users in the subgroup over age 65 were as follows:

• Myocardial infarction—RR 0.66, 95% CI 0.44–0.97, P = .04
• Composite end point—RR 0.74, 95% CI 0.59–0.92, P = .008.

Aspirin was taken every other day and at a higher dose than the 81 mg recommended in the United States, although it is unclear how these differences may have affected the results.

United States Preventive Services Task Force (USPSTF) recommendations. Although the USPSTF currently recommends aspirin for men age 45 to 79 to prevent myocardial infarction, it offers no such recommendation for women, largely because of the results of the Women’s Health Initiative study. However, it does recommend aspirin to prevent ischemic stroke in women age 55 to 79.³ Additionally, aspirin can be considered for prevention of myocardial infarction in women who are over age 65 or at high risk.⁶

This is based on Women’s Health Study data for women over age 65 showing a number needed to treat of 47 to prevent 1 cardiovascular event, whereas the number needed to harm, defined by a major hemorrhagic event, was 128. In contrast, in women younger than age 65, the number needed to treat was 2,001 and the number needed to harm was 196.⁴

High-risk features, as defined by the guidelines, are a history of coronary artery disease, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes, or chronic kidney disease, or a 10-year predicted risk of cardiovascular disease of more than 10%.

Jardine et al⁷ reported that aspirin was beneficial in patients with chronic kidney disease. The rates of cardiovascular death, death from any cause, and stroke were significantly lower in patients with a glomerular filtration rate (GFR) less than 45 mL/min if they received aspirin. The rates were also lower in aspirin recipients with a GFR between 46 and 60 mL/min, but the difference was not statistically significant.

Comments. Given the risk of significant gastrointestinal bleeding and a trend toward hemorrhagic stroke with aspirin use,⁴ it is important to weigh the risks and benefits of aspirin for primary prevention in women.

Our understanding of the reasons for sex differences in the clinical benefits of aspirin for primary prevention is limited at this point. Studies have shown a higher prevalence of platelet reactivity and aspirin resistance in women than in men, suggesting that hormonal differences may play a role.⁸ There has been mention of using higher doses of aspirin in women to achieve the same level of platelet inhibition as in men. However, studies have shown essentially equal platelet inhibition in both men and women after aspirin administration.⁹ Therefore, more work needs to be done to better understand the observed sex differences in response to aspirin.

Given suggestions that statins may not be effective in women¹⁰ and the fact that women were underrepresented in earlier statin trials, a number of studies have examined this issue in the last several years.

The JUPITER trial (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin)¹⁰ enrolled patients who had no history of coronary artery disease and who had a C-reactive protein level equal to or greater than 2 mg/L and a low-density lipoprotein cholesterol level of less than 130 mg/dL. (Of note, these patients would not have met the criteria for receiving a statin for primary prevention according to the current Adult Treatment Panel guidelines.)

The women in the trial who received rosuvastatin had a 46% lower incidence of myocardial infarction, stroke, revascularization, hospitalization for unstable angina, or death from cardiovascular causes. In addition, a meta-analysis performed by the authors showed a one-third reduction of cardiovascular disease end points in women. However, there was no reduction in the mortality rate.

Reprinted from Kostis WJ, et al. Meta-analysis of statin effects in women versus men. J Am Coll Cardiol 2012; 59:572–582, with permission from Elsevier.

Other statin trials. A later meta-analysis of randomized primary prevention trials found that men and women derived similar benefit from statins in terms of cardiovascular disease end points and all-cause mortality (Figure 1),¹¹ although five of the trials included a small number of secondary prevention patients. In contrast, a meta-analysis of only primary prevention patients showed no benefit of statin therapy in all-cause mortality, although the authors acknowledged that there were insufficient data to look specifically at women in this sample.¹²

A Cochrane review conducted before the JUPITER data were available concluded that there was insufficient evidence to prescribe statins for primary prevention in patients at low cardiovascular risk.13 However, an updated version that included results of the JUPITER trial concluded that there was a reduction in the rate of all-cause mortality and cardiovascular events in both men and women receiving a statin for primary prevention.14

Given these conflicting results, debate continues as to the benefit of statins for primary prevention, not only in women but in the population as a whole.^15,16 The definition of high risk, in terms of comorbidities and lipid profile, also continues to evolve and will likely be an important factor in identifying women who will benefit from statin therapy for primary prevention.

Statin adverse effects. Much of the debate about statins for primary prevention stems from concern about the adverse effects of these drugs. In addition to myopathy, there have been reports of increased risks of new diabetes and cognitive impairment.¹⁶ In a post hoc analysis of the Women’s Health Initiative, the adjusted risk of diabetes was 48% higher in women taking a statin for primary prevention than in similar women not taking a statin.¹⁷ (This finding should be viewed with caution, since the data are observational.)

There has also been a question of whether women experience more side effects from statin therapy than men do. Although thin or frail women over age 80 are more susceptible to statin side effects, this finding has not been observed in younger women.¹⁸

Comment. In view of the data, it appears reasonable to consider statin therapy for primary prevention in women deemed to be at high risk based on the current guidelines. However, as always, one must consider whether the benefits outweigh the risks for the individual patient. More study is needed to better evaluate the utility of statin therapy in primary prevention.

Hormone therapy

Hormone therapy has received enormous attention in both the medical community and the public media. (Hormone therapy is either combined estrogen and progestin or estrogen alone, used to treat symptoms of menopause and to prevent osteoporosis in postmenopausal women. Here, we will discuss hormone therapy and not hormone replacement therapy, which is used specifically to treat premature menopause.)

The safety of estrogen-progestin combination therapy has been the subject of great debate since a Women’s Health Initiative study showed a trend toward a greater risk of cardiovascular disease in estrogen-progestin users.¹⁹

Women who received estrogen by itself showed no difference in cardiovascular risk compared with those who received placebo. Unopposed estrogen is rarely prescribed, since it increases the risk of endometrial cancer in women who have not undergone hysterectomy.²⁰

Both unopposed estrogen and combination therapy have also been found to increase the risk of stroke,²⁰ deep vein thrombosis, gallbladder disease, and certain forms of urinary incontinence.

Guidelines on hormone therapy. The USPSTF does not recommend hormone therapy to prevent chronic conditions, basing its decision on the findings from the Women’s Health Initiative.²¹ The American College of Cardiology and American Heart Association (ACC/AHA) 2007 guidelines advise against continuing hormone therapy in patients who present with acute coronary syndrome, although recommendations need to address a broader scope of primary and secondary prevention patients.

Does timing matter? There is a hypothesis that when hormone therapy is started may affect the cardiovascular risk. A secondary analysis of the Women’s Health Initiative study²² showed a trend towards less cardiovascular disease in women who started hormone therapy within 9 years of menopause, whereas those starting it later had a statistically significantly higher rate of cardiovascular mortality. However, all women had a higher risk of stroke while on hormone therapy, regardless of timing.²²

A study of 1,006 healthy women age 45 to 58 whose last menstrual period was 3 to 24 months before enrollment found a statistically significant reduction in the composite end point of death, hospital admission for myocardial infarction, or heart failure with hormone therapy.²³ There was no significant increase in breast cancer, deep vein thrombosis, or stroke after 10 years of randomized treatment.

A retrospective analysis of 71,237 postmenopausal women in the California Teachers Study also found a significant reduction in the rate of cardiovascular disease-related deaths with hormone therapy in younger women (ie, younger than age 65), but not in older women.²⁴ The authors concluded that it may not just be the years after menopause but also the baseline age of the woman that may influence outcomes.

In view of these studies, there is increasing recognition that hormone therapy may, in fact, still be beneficial in terms of cardiovascular and all-cause mortality in carefully selected patients. The cardiovascular risk in women, specifically older women who have had a longer duration of menopause, should also be weighed against the potential benefits of therapy in terms of quality of life and symptom relief.

Trials under way include the Kronos Early Estrogen Prevention (KEEP) and Danish Osteoporosis Prevention (DOPS) studies. KEEP is a 4-year, double-blind, randomized controlled trial of hormone therapy in women within 3 years of menopause. DOPS is an open-label trial that includes more than 1,000 women with early menopause. The results of these trials will likely affect future recommendations.

WOMEN’S SYMPTOMS: TYPICAL OR ATYPICAL?

Whether the presenting symptoms of acute coronary syndromes differ between men and women has been much debated.

More women than men seem to present with atypical symptoms.^25–27 (The term “atypical” refers to symptoms that do not include the three classic components of angina: substernal chest pain or discomfort, provoked by exertion or emotional stress, and relieved by rest or nitroglycerin, or both.²⁸)

However, most women still present with chest pain. In a study by Dey et al,²⁶ 92% of the 7,638 women with presumed acute coronary syndrome presented with chest pain. In women who had atypical symptoms, dyspnea, nausea, vomiting, and diaphoresis were the most common symptoms. Women were significantly more likely than men to present with nausea and vomiting (32% vs 23%, P = .001).

Women in the study were also more likely to have angiographically normal coronary arteries (12% vs 6%, P < .001).²⁶ This difference may be largely due to noncardiac chest pain, but it may also represent conditions such as vasospasm, microvascular disease, or stress cardiomyopathy, all of which disproportionately affect women.

An earlier review of 10 major studies found a higher percentage of women presenting with atypical symptoms (37.5% of women vs 27.4% of men).²⁵ However, symptoms were not a focus of these studies, and the findings may therefore be skewed by inaccurate documentation.

Atypical warning signs. Although most women with acute coronary syndrome present acutely with chest pain, women may have different warning signs than men. Only about one-third of women experience angina before presentation.²⁹ Compared with men, women are more likely to complain of shortness of breath, fatigue, and weakness leading up to a diagnosis of a myocardial infarction.²⁹ Therefore, the prodromal symptoms of cardiovascular disease may in fact be significantly more atypical in women than in men, suggesting the need for heightened vigilance in the cardiovascular evaluation of women who have nonanginal symptoms.

THE ROLE OF STRESS TESTING IN WOMEN

Stress testing in various forms continues to be widely used in the diagnosis of heart disease in women, although data are scarce regarding its utility in women.

The ACC/AHA guidelines continue to recommend exercise stress electrocardiography (ECG) for women who have symptoms, are at intermediate risk, and have a normal result on resting ECG.³⁰

Exercise ECG has a higher false-positive rate in women than in men,³¹ and there appears to be no relationship between exercise-induced ST-segment depression and the rate of cardiovascular mortality or all-cause mortality in women.^32,33 On the other hand, exercise ECG yields valuable additional information such as exercise capacity, chronotropic response, heart-rate recovery, and blood pressure response, all of which have important diagnostic and prognostic implications in women.³⁴

For those who have an abnormal resting ECG, the addition of an imaging test, ie, echocardiography or single-photon emission computed tomography (SPECT), is indicated. Both have limitations: SPECT can give false-positive results because of breast attenuation, and echocardiography varies in accuracy depending on the quality of acoustic windows obtained. Both exercise stress SPECT and exercise stress ECG have higher sensitivity and specificity than electrocardiographic exercise stress testing alone,³⁴ and there is evidence that the two imaging tests are comparable in women.³⁵

In those women who have baseline left bundle branch block or who cannot exercise, a pharmacologic stress test should be performed. Of course, this is a less desirable testing method, given the loss of valuable information obtained from exercising the patient.

UNDERLYING CONDITIONS THAT DISPROPORTIONATELY AFFECT WOMEN

Microvascular angina

Perimenopausal and postmenopausal women account for 70% of patients presenting with chest pain and elevated cardiac enzymes but no significant angiographic evidence of coronary artery disease.³⁶ This condition, commonly called syndrome X, is often characterized by lingering, dull chest pain after exertion and is seen more frequently in women younger than those presenting with classic cardiovascular disease.

Because at least some of these patients show evidence of ST-segment depression and reversible perfusion defects on imaging, the condition is thought to be caused by ischemia of the microvascular bed leading to microvascular angina.³⁷

Although this is still an area of research, microvascular dysfunction has recently been proposed as an explanation for these findings. Abnormal vasoconstriction and impaired vasodilation of the microvascular bed, insulin resistance, increased systemic inflammation, and abnormal pain response have all been cited as potentially contributing to microvascular dysfunction.³⁶

Estrogen deficiency is thought to play a central role in the significantly increased burden of microvascular dysfunction seen in women, with some studies suggesting that hormone therapy can relieve symptoms. However, given the concerns about adverse cardiovascular outcomes in women on hormone therapy, there has been little investigation of this treatment for this disorder.

Studies have shown worse cardiovascular outcomes and higher rates of angina-related hospitalization and repeat heart catheterizations in women with microvascular dysfunction.³⁸

Diagnosing microvascular angina must be done indirectly, as there is no safe and minimally invasive technique by which to directly observe the microvasculature. Current coronary angiographic techniques cannot image vessels smaller than 0.5 mm in diameter, and endomyocardial biopsy cannot access the larger periarterioles thought to play a major role in regulating coronary blood flow.³⁹

Image courtesy of Dr. Deborah Kwon

Because the coronary microvasculature controls total coronary resistance and therefore regulates myocardial blood flow, measuring myocardial blood flow at maximum vasodilation, termed coronary flow reserve, can indirectly evaluate the degree of microvascular dysfunction.⁴⁰ In the absence of obstructive epicardial coronary disease, noninvasive imaging techniques or provocative testing in the coronary catheterization lab can be used for this purpose. In terms of noninvasive imaging, perfusion magnetic resonance imaging (Figure 2) or positron emission tomography is often performed.⁴⁰

Coronary flow reserve can also be measured by invasive means in the catheterization laboratory after maximum hyperemia is induced by adenosine or other such vasodilatory agents.⁴¹ However, measurements obtained in this invasive manner are greatly affected by hemodynamic changes and can have poor reproducibility.⁴⁰

Proposed therapy for microvascular angina. Once a diagnosis has been made, lifestyle modification, antianginal agents, angiotensin-converting enzyme inhibitors, and statins have been suggested for therapy.³⁹ Pain management techniques are also used, given the increased pain sensitivity observed in women with this condition. However, no therapy to date has proven overwhelmingly effective in these patients, and a disproportionate number of women suffer from chronic symptoms despite these treatments. Currently, researchers are looking for new agents to treat microvascular disease.

Stress cardiomyopathy

Images courtesy of Dr. Michael Faulx and Dr. Shikhar Agarwal

Stress cardiomyopathy, also called takotsubo cardiomyopathy or “broken heart syndrome,” is another condition that disproportionately affects postmenopausal women. It is often associated with sudden emotional or physical stress. Patients present with signs and symptoms of myocardial infarction without demonstrable epicardial coronary artery disease. The hallmark of stress cardiomyopathy is left ventricular dysfunction, often severe, with classic apical ballooning that resembles a Japanese fishing pot (takotsubo) used to trap octopuses, hence the name (Figure 3).

According to a review by Akashi et al⁴² based on previously reported Mayo Clinic criteria, the diagnosis of stress cardiomyopathy includes each of the following:

• Transient hypokinesis, akinesis, or dyskinesis in the left ventricular midsegments with or without apical involvement; regional wall-motion abnormalities that extend beyond a single epicardial vascular distribution; and frequently, but not always, a stressful trigger
• Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture
• New abnormality on ECG (eg, ST-segment elevation, T-wave inversion) or modest elevation in cardiac troponin
• Absence of pheochromocytoma or myocarditis.

From 80% to 100% of reported cases are in women, with an average age range of 61 to 76.⁴² It is unclear why there is such an overwhelming postmenopausal female preponderance of the disease. Studies have implicated estrogen deficiency, as it appears to attenuate the levels of cardioprotective substances in the body that in part regulate catecholamine surges and may also increase the level of oxidative stress.⁴²

Several mechanisms for this condition have been proposed. The condition may be caused by multivessel epicardial coronary spasm or spontaneously resolved plaque rupture, resulting in stunned myocardium. However, the regional distribution of wall-motion abnormality is often out of proportion to the level of cardiac enzyme elevation, and in the case of plaque rupture, is frequently not consistent with a single coronary vessel.⁴² A catecholamine surge causing myocardial and neurogenic stunning has also been proposed, although many of these patients have normal catecholamine levels.⁴² Finally, microvascular dysfunction has been found in a number of patients with this condition. However, it is difficult to establish a causal relationship, since apical ballooning could result in microvascular dysfunction.⁴²

Treatment of stress cardiomyopathy has not been standardized, in part because the left ventricular dysfunction often resolves spontaneously within several weeks.^43,44 Given the proposed catecholaminergic mechanism, some experts believe that beta-blockers are contraindicated because of the resulting unopposed activation of alpha-adrenoreceptors. However, this continues to be a matter of debate. There is also no clear indication for other standard therapies for acute coronary syndrome such as aspirin and heparin, and their use appears to vary in clinical practice.

Although most patients improve with time and recurrence is exceedingly rare, it should be emphasized that they may present acutely with severe hemodynamic instability and cardiogenic shock. Therefore, advanced means of support, such as an intra-aortic balloon pump, may be indicated until the patient recovers from the acute phase of the disease.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome resulting from dissection of the coronary intimal or medial layer and associated hematoma formation, leading to coronary occlusion.^45,46 In a case series of 87 patients, 49% presented with an ST-segment elevation myocardial infarction, and 23% were found to have multivessel SCAD.⁴⁶

SCAD occurs predominantly in young, healthy women (mean age 30–45 years). Approximately 70% of cases are in women, 30% of whom are in the peripartum period.⁴⁵ The reasons for the increased risk during pregnancy have not yet been elucidated, but changing sex hormones, increased cardiac output and shear stress, and an increased inflammatory response have been implicated.⁴⁵

Diagnosing SCAD. Coronary angiography should be performed with extreme caution in patients suspected of having SCAD, given the risk of further dissection of the artery with forceful injections. In certain cases, it may be difficult to detect SCAD on routine angiography if there is no communication between the true and false lumen.

If the suspicion for SCAD is high, intravascular ultrasonography or optical coherence tomography can be used to better evaluate the vessel.⁴⁵ Although optical coherence tomography has greater spatial resolution, it is more costly and is not as widely used as intravascular ultrasonography in the clinical setting

Managing SCAD. Although conservative management and coronary artery bypass grafting have been shown to cause minimal in-hospital morbidity, percutaneous coronary intervention has been complicated by technical failure in up to 35% of patients in one series.⁴⁶

While there is no standardized way to manage these patients, experts currently recommend conservative management with standard therapies for acute coronary syndrome (Figure 4). Although antithrombotic agents can decrease thrombus burden, they must be used with caution, because they also increase the risk of bleeding into the false lumen.

If patients experience recurrent or ongoing ischemia despite conservative management, then revascularization should be considered. Optical coherence tomography or intravascular ultrasonography is recommended to ensure proper stent alignment and positioning.

Coronary artery bypass grafting could be considered in preference to percutaneous coronary intervention, given that the former appears to be safer,⁴⁶ although this requires further investigation. Some studies have cautioned against using fibrinolytic therapy, based on anecdotal evidence that it may further propagate the dissection,⁴⁵ although this therapy has been used in other case studies.⁴⁶

While mortality rates are relatively low (95% survival at 2 years),⁴⁵ the estimated risk of recurrent SCAD at 10 years is approximately 30%.⁴⁶

Image courtesy of Dr. Heather Gornik

Associated with fibromuscular dysplasia. Of note, a sizeable number of patients with SCAD have been found to have fibromuscular dysplasia. This is a nonatherosclerotic, noninflammatory vascular condition that can affect any vascular bed in the body, although there is a predilection for the renal and carotid arteries (Figure 5).⁴⁷ Fibromuscular dysplasia also disproportionately affects women and appears to be a concomitant condition in the majority of patients with SCAD.⁴⁷ Imaging of the carotid and renal arteries of patients with SCAD has revealed a number of cases of fibromuscular dysplasia.^46,48 This noted association will likely allow for ongoing research to better understand the pathophysiology of these two conditions.

Although long considered a disease of elderly men, cardiovascular disease is increasingly recognized for its impact on women. In fact, it is now the leading cause of death in women worldwide, and in the United States more women than men die of it.¹

Given this epidemic of cardiovascular disease in women, more research is now being dedicated to identifying sex-specific aspects of cardiovascular disease, the better to prevent and treat it.

This review will focus on the most recent information about how prevention, symptoms, and underlying cardiovascular conditions differ in women.

PRIMARY PREVENTION: ONGOING DEBATE

Women who diet, exercise, and abstain from smoking have an 80% lower rate of cardiovascular events than the female population overall.² However, beyond lifestyle modification and blood pressure control, there is ongoing debate as to the efficacy of our available therapies for preventing cardiovascular disease in women.

Aspirin for primary prevention in women: No benefit?

The use of aspirin to prevent cardiovascular disease in women has long been controversial. Several trials showed a lower rate of myocardial infarction in people using aspirin for primary prevention, but most of the patients in the initial trials were men (Table 1).³

The Women’s Health Study⁴ assigned 39,876 women age 45 and older to receive either aspirin (100 mg on alternate days) or placebo, and monitored them for more than 10 years for major cardiovascular events (non-fatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes).

The results, published in 2005, showed that the rates of myocardial infarction and cardiovascular death were not significantly lower in the aspirin group, although the rate of ischemic stroke was 24% lower. There were more hemorrhagic strokes in the aspirin group (not statistically significant), and there was significantly more gastrointestinal bleeding. The study showed the relative risk (RR) and 95% confidence interval (CI) for several outcomes in aspirin users were:

• Myocardial infarction—RR 1.02, 95% CI 0.84–1.25, P = .83
• Cardiovascular death—RR 0.95, 95% CI 0.74–1.22, P = .68
• Ischemic stroke—RR 0.76, 95% CI 0.63–0.93, P = .009
• Hemorrhagic stroke—RR 1.24, 95% CI 0.82–1.87, P = .31
• Gastrointestinal bleeding—RR 1.4, 95% CI 1.07–1.83, P = .02.

A later analysis indicated that noncompliance had no effect on these results.⁵

However, a subgroup analysis of women over age 65 found a significant reduction in the rate of myocardial infarction and in the composite end point of myocardial infarction, stroke, and cardiovascular death, although there was a trend toward a higher rate of gastrointestinal bleeding. The numbers in aspirin users in the subgroup over age 65 were as follows:

• Myocardial infarction—RR 0.66, 95% CI 0.44–0.97, P = .04
• Composite end point—RR 0.74, 95% CI 0.59–0.92, P = .008.

Aspirin was taken every other day and at a higher dose than the 81 mg recommended in the United States, although it is unclear how these differences may have affected the results.

United States Preventive Services Task Force (USPSTF) recommendations. Although the USPSTF currently recommends aspirin for men age 45 to 79 to prevent myocardial infarction, it offers no such recommendation for women, largely because of the results of the Women’s Health Initiative study. However, it does recommend aspirin to prevent ischemic stroke in women age 55 to 79.³ Additionally, aspirin can be considered for prevention of myocardial infarction in women who are over age 65 or at high risk.⁶

This is based on Women’s Health Study data for women over age 65 showing a number needed to treat of 47 to prevent 1 cardiovascular event, whereas the number needed to harm, defined by a major hemorrhagic event, was 128. In contrast, in women younger than age 65, the number needed to treat was 2,001 and the number needed to harm was 196.⁴

High-risk features, as defined by the guidelines, are a history of coronary artery disease, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes, or chronic kidney disease, or a 10-year predicted risk of cardiovascular disease of more than 10%.

Jardine et al⁷ reported that aspirin was beneficial in patients with chronic kidney disease. The rates of cardiovascular death, death from any cause, and stroke were significantly lower in patients with a glomerular filtration rate (GFR) less than 45 mL/min if they received aspirin. The rates were also lower in aspirin recipients with a GFR between 46 and 60 mL/min, but the difference was not statistically significant.

Comments. Given the risk of significant gastrointestinal bleeding and a trend toward hemorrhagic stroke with aspirin use,⁴ it is important to weigh the risks and benefits of aspirin for primary prevention in women.

Our understanding of the reasons for sex differences in the clinical benefits of aspirin for primary prevention is limited at this point. Studies have shown a higher prevalence of platelet reactivity and aspirin resistance in women than in men, suggesting that hormonal differences may play a role.⁸ There has been mention of using higher doses of aspirin in women to achieve the same level of platelet inhibition as in men. However, studies have shown essentially equal platelet inhibition in both men and women after aspirin administration.⁹ Therefore, more work needs to be done to better understand the observed sex differences in response to aspirin.

Given suggestions that statins may not be effective in women¹⁰ and the fact that women were underrepresented in earlier statin trials, a number of studies have examined this issue in the last several years.

The JUPITER trial (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin)¹⁰ enrolled patients who had no history of coronary artery disease and who had a C-reactive protein level equal to or greater than 2 mg/L and a low-density lipoprotein cholesterol level of less than 130 mg/dL. (Of note, these patients would not have met the criteria for receiving a statin for primary prevention according to the current Adult Treatment Panel guidelines.)

The women in the trial who received rosuvastatin had a 46% lower incidence of myocardial infarction, stroke, revascularization, hospitalization for unstable angina, or death from cardiovascular causes. In addition, a meta-analysis performed by the authors showed a one-third reduction of cardiovascular disease end points in women. However, there was no reduction in the mortality rate.

Reprinted from Kostis WJ, et al. Meta-analysis of statin effects in women versus men. J Am Coll Cardiol 2012; 59:572–582, with permission from Elsevier.

Other statin trials. A later meta-analysis of randomized primary prevention trials found that men and women derived similar benefit from statins in terms of cardiovascular disease end points and all-cause mortality (Figure 1),¹¹ although five of the trials included a small number of secondary prevention patients. In contrast, a meta-analysis of only primary prevention patients showed no benefit of statin therapy in all-cause mortality, although the authors acknowledged that there were insufficient data to look specifically at women in this sample.¹²

A Cochrane review conducted before the JUPITER data were available concluded that there was insufficient evidence to prescribe statins for primary prevention in patients at low cardiovascular risk.13 However, an updated version that included results of the JUPITER trial concluded that there was a reduction in the rate of all-cause mortality and cardiovascular events in both men and women receiving a statin for primary prevention.14

Given these conflicting results, debate continues as to the benefit of statins for primary prevention, not only in women but in the population as a whole.^15,16 The definition of high risk, in terms of comorbidities and lipid profile, also continues to evolve and will likely be an important factor in identifying women who will benefit from statin therapy for primary prevention.

Statin adverse effects. Much of the debate about statins for primary prevention stems from concern about the adverse effects of these drugs. In addition to myopathy, there have been reports of increased risks of new diabetes and cognitive impairment.¹⁶ In a post hoc analysis of the Women’s Health Initiative, the adjusted risk of diabetes was 48% higher in women taking a statin for primary prevention than in similar women not taking a statin.¹⁷ (This finding should be viewed with caution, since the data are observational.)

There has also been a question of whether women experience more side effects from statin therapy than men do. Although thin or frail women over age 80 are more susceptible to statin side effects, this finding has not been observed in younger women.¹⁸

Comment. In view of the data, it appears reasonable to consider statin therapy for primary prevention in women deemed to be at high risk based on the current guidelines. However, as always, one must consider whether the benefits outweigh the risks for the individual patient. More study is needed to better evaluate the utility of statin therapy in primary prevention.

Hormone therapy

Hormone therapy has received enormous attention in both the medical community and the public media. (Hormone therapy is either combined estrogen and progestin or estrogen alone, used to treat symptoms of menopause and to prevent osteoporosis in postmenopausal women. Here, we will discuss hormone therapy and not hormone replacement therapy, which is used specifically to treat premature menopause.)

The safety of estrogen-progestin combination therapy has been the subject of great debate since a Women’s Health Initiative study showed a trend toward a greater risk of cardiovascular disease in estrogen-progestin users.¹⁹

Women who received estrogen by itself showed no difference in cardiovascular risk compared with those who received placebo. Unopposed estrogen is rarely prescribed, since it increases the risk of endometrial cancer in women who have not undergone hysterectomy.²⁰

Both unopposed estrogen and combination therapy have also been found to increase the risk of stroke,²⁰ deep vein thrombosis, gallbladder disease, and certain forms of urinary incontinence.

Guidelines on hormone therapy. The USPSTF does not recommend hormone therapy to prevent chronic conditions, basing its decision on the findings from the Women’s Health Initiative.²¹ The American College of Cardiology and American Heart Association (ACC/AHA) 2007 guidelines advise against continuing hormone therapy in patients who present with acute coronary syndrome, although recommendations need to address a broader scope of primary and secondary prevention patients.

Does timing matter? There is a hypothesis that when hormone therapy is started may affect the cardiovascular risk. A secondary analysis of the Women’s Health Initiative study²² showed a trend towards less cardiovascular disease in women who started hormone therapy within 9 years of menopause, whereas those starting it later had a statistically significantly higher rate of cardiovascular mortality. However, all women had a higher risk of stroke while on hormone therapy, regardless of timing.²²

A study of 1,006 healthy women age 45 to 58 whose last menstrual period was 3 to 24 months before enrollment found a statistically significant reduction in the composite end point of death, hospital admission for myocardial infarction, or heart failure with hormone therapy.²³ There was no significant increase in breast cancer, deep vein thrombosis, or stroke after 10 years of randomized treatment.

A retrospective analysis of 71,237 postmenopausal women in the California Teachers Study also found a significant reduction in the rate of cardiovascular disease-related deaths with hormone therapy in younger women (ie, younger than age 65), but not in older women.²⁴ The authors concluded that it may not just be the years after menopause but also the baseline age of the woman that may influence outcomes.

In view of these studies, there is increasing recognition that hormone therapy may, in fact, still be beneficial in terms of cardiovascular and all-cause mortality in carefully selected patients. The cardiovascular risk in women, specifically older women who have had a longer duration of menopause, should also be weighed against the potential benefits of therapy in terms of quality of life and symptom relief.

Trials under way include the Kronos Early Estrogen Prevention (KEEP) and Danish Osteoporosis Prevention (DOPS) studies. KEEP is a 4-year, double-blind, randomized controlled trial of hormone therapy in women within 3 years of menopause. DOPS is an open-label trial that includes more than 1,000 women with early menopause. The results of these trials will likely affect future recommendations.

WOMEN’S SYMPTOMS: TYPICAL OR ATYPICAL?

Whether the presenting symptoms of acute coronary syndromes differ between men and women has been much debated.

More women than men seem to present with atypical symptoms.^25–27 (The term “atypical” refers to symptoms that do not include the three classic components of angina: substernal chest pain or discomfort, provoked by exertion or emotional stress, and relieved by rest or nitroglycerin, or both.²⁸)

However, most women still present with chest pain. In a study by Dey et al,²⁶ 92% of the 7,638 women with presumed acute coronary syndrome presented with chest pain. In women who had atypical symptoms, dyspnea, nausea, vomiting, and diaphoresis were the most common symptoms. Women were significantly more likely than men to present with nausea and vomiting (32% vs 23%, P = .001).

Women in the study were also more likely to have angiographically normal coronary arteries (12% vs 6%, P < .001).²⁶ This difference may be largely due to noncardiac chest pain, but it may also represent conditions such as vasospasm, microvascular disease, or stress cardiomyopathy, all of which disproportionately affect women.

An earlier review of 10 major studies found a higher percentage of women presenting with atypical symptoms (37.5% of women vs 27.4% of men).²⁵ However, symptoms were not a focus of these studies, and the findings may therefore be skewed by inaccurate documentation.

Atypical warning signs. Although most women with acute coronary syndrome present acutely with chest pain, women may have different warning signs than men. Only about one-third of women experience angina before presentation.²⁹ Compared with men, women are more likely to complain of shortness of breath, fatigue, and weakness leading up to a diagnosis of a myocardial infarction.²⁹ Therefore, the prodromal symptoms of cardiovascular disease may in fact be significantly more atypical in women than in men, suggesting the need for heightened vigilance in the cardiovascular evaluation of women who have nonanginal symptoms.

THE ROLE OF STRESS TESTING IN WOMEN

Stress testing in various forms continues to be widely used in the diagnosis of heart disease in women, although data are scarce regarding its utility in women.

The ACC/AHA guidelines continue to recommend exercise stress electrocardiography (ECG) for women who have symptoms, are at intermediate risk, and have a normal result on resting ECG.³⁰

Exercise ECG has a higher false-positive rate in women than in men,³¹ and there appears to be no relationship between exercise-induced ST-segment depression and the rate of cardiovascular mortality or all-cause mortality in women.^32,33 On the other hand, exercise ECG yields valuable additional information such as exercise capacity, chronotropic response, heart-rate recovery, and blood pressure response, all of which have important diagnostic and prognostic implications in women.³⁴

For those who have an abnormal resting ECG, the addition of an imaging test, ie, echocardiography or single-photon emission computed tomography (SPECT), is indicated. Both have limitations: SPECT can give false-positive results because of breast attenuation, and echocardiography varies in accuracy depending on the quality of acoustic windows obtained. Both exercise stress SPECT and exercise stress ECG have higher sensitivity and specificity than electrocardiographic exercise stress testing alone,³⁴ and there is evidence that the two imaging tests are comparable in women.³⁵

In those women who have baseline left bundle branch block or who cannot exercise, a pharmacologic stress test should be performed. Of course, this is a less desirable testing method, given the loss of valuable information obtained from exercising the patient.

UNDERLYING CONDITIONS THAT DISPROPORTIONATELY AFFECT WOMEN

Microvascular angina

Perimenopausal and postmenopausal women account for 70% of patients presenting with chest pain and elevated cardiac enzymes but no significant angiographic evidence of coronary artery disease.³⁶ This condition, commonly called syndrome X, is often characterized by lingering, dull chest pain after exertion and is seen more frequently in women younger than those presenting with classic cardiovascular disease.

Because at least some of these patients show evidence of ST-segment depression and reversible perfusion defects on imaging, the condition is thought to be caused by ischemia of the microvascular bed leading to microvascular angina.³⁷

Although this is still an area of research, microvascular dysfunction has recently been proposed as an explanation for these findings. Abnormal vasoconstriction and impaired vasodilation of the microvascular bed, insulin resistance, increased systemic inflammation, and abnormal pain response have all been cited as potentially contributing to microvascular dysfunction.³⁶

Estrogen deficiency is thought to play a central role in the significantly increased burden of microvascular dysfunction seen in women, with some studies suggesting that hormone therapy can relieve symptoms. However, given the concerns about adverse cardiovascular outcomes in women on hormone therapy, there has been little investigation of this treatment for this disorder.

Studies have shown worse cardiovascular outcomes and higher rates of angina-related hospitalization and repeat heart catheterizations in women with microvascular dysfunction.³⁸

Diagnosing microvascular angina must be done indirectly, as there is no safe and minimally invasive technique by which to directly observe the microvasculature. Current coronary angiographic techniques cannot image vessels smaller than 0.5 mm in diameter, and endomyocardial biopsy cannot access the larger periarterioles thought to play a major role in regulating coronary blood flow.³⁹

Image courtesy of Dr. Deborah Kwon

Because the coronary microvasculature controls total coronary resistance and therefore regulates myocardial blood flow, measuring myocardial blood flow at maximum vasodilation, termed coronary flow reserve, can indirectly evaluate the degree of microvascular dysfunction.⁴⁰ In the absence of obstructive epicardial coronary disease, noninvasive imaging techniques or provocative testing in the coronary catheterization lab can be used for this purpose. In terms of noninvasive imaging, perfusion magnetic resonance imaging (Figure 2) or positron emission tomography is often performed.⁴⁰

Coronary flow reserve can also be measured by invasive means in the catheterization laboratory after maximum hyperemia is induced by adenosine or other such vasodilatory agents.⁴¹ However, measurements obtained in this invasive manner are greatly affected by hemodynamic changes and can have poor reproducibility.⁴⁰

Proposed therapy for microvascular angina. Once a diagnosis has been made, lifestyle modification, antianginal agents, angiotensin-converting enzyme inhibitors, and statins have been suggested for therapy.³⁹ Pain management techniques are also used, given the increased pain sensitivity observed in women with this condition. However, no therapy to date has proven overwhelmingly effective in these patients, and a disproportionate number of women suffer from chronic symptoms despite these treatments. Currently, researchers are looking for new agents to treat microvascular disease.

Stress cardiomyopathy

Images courtesy of Dr. Michael Faulx and Dr. Shikhar Agarwal

Stress cardiomyopathy, also called takotsubo cardiomyopathy or “broken heart syndrome,” is another condition that disproportionately affects postmenopausal women. It is often associated with sudden emotional or physical stress. Patients present with signs and symptoms of myocardial infarction without demonstrable epicardial coronary artery disease. The hallmark of stress cardiomyopathy is left ventricular dysfunction, often severe, with classic apical ballooning that resembles a Japanese fishing pot (takotsubo) used to trap octopuses, hence the name (Figure 3).

According to a review by Akashi et al⁴² based on previously reported Mayo Clinic criteria, the diagnosis of stress cardiomyopathy includes each of the following:

• Transient hypokinesis, akinesis, or dyskinesis in the left ventricular midsegments with or without apical involvement; regional wall-motion abnormalities that extend beyond a single epicardial vascular distribution; and frequently, but not always, a stressful trigger
• Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture
• New abnormality on ECG (eg, ST-segment elevation, T-wave inversion) or modest elevation in cardiac troponin
• Absence of pheochromocytoma or myocarditis.

From 80% to 100% of reported cases are in women, with an average age range of 61 to 76.⁴² It is unclear why there is such an overwhelming postmenopausal female preponderance of the disease. Studies have implicated estrogen deficiency, as it appears to attenuate the levels of cardioprotective substances in the body that in part regulate catecholamine surges and may also increase the level of oxidative stress.⁴²

Several mechanisms for this condition have been proposed. The condition may be caused by multivessel epicardial coronary spasm or spontaneously resolved plaque rupture, resulting in stunned myocardium. However, the regional distribution of wall-motion abnormality is often out of proportion to the level of cardiac enzyme elevation, and in the case of plaque rupture, is frequently not consistent with a single coronary vessel.⁴² A catecholamine surge causing myocardial and neurogenic stunning has also been proposed, although many of these patients have normal catecholamine levels.⁴² Finally, microvascular dysfunction has been found in a number of patients with this condition. However, it is difficult to establish a causal relationship, since apical ballooning could result in microvascular dysfunction.⁴²

Treatment of stress cardiomyopathy has not been standardized, in part because the left ventricular dysfunction often resolves spontaneously within several weeks.^43,44 Given the proposed catecholaminergic mechanism, some experts believe that beta-blockers are contraindicated because of the resulting unopposed activation of alpha-adrenoreceptors. However, this continues to be a matter of debate. There is also no clear indication for other standard therapies for acute coronary syndrome such as aspirin and heparin, and their use appears to vary in clinical practice.

Although most patients improve with time and recurrence is exceedingly rare, it should be emphasized that they may present acutely with severe hemodynamic instability and cardiogenic shock. Therefore, advanced means of support, such as an intra-aortic balloon pump, may be indicated until the patient recovers from the acute phase of the disease.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome resulting from dissection of the coronary intimal or medial layer and associated hematoma formation, leading to coronary occlusion.^45,46 In a case series of 87 patients, 49% presented with an ST-segment elevation myocardial infarction, and 23% were found to have multivessel SCAD.⁴⁶

SCAD occurs predominantly in young, healthy women (mean age 30–45 years). Approximately 70% of cases are in women, 30% of whom are in the peripartum period.⁴⁵ The reasons for the increased risk during pregnancy have not yet been elucidated, but changing sex hormones, increased cardiac output and shear stress, and an increased inflammatory response have been implicated.⁴⁵

Diagnosing SCAD. Coronary angiography should be performed with extreme caution in patients suspected of having SCAD, given the risk of further dissection of the artery with forceful injections. In certain cases, it may be difficult to detect SCAD on routine angiography if there is no communication between the true and false lumen.

If the suspicion for SCAD is high, intravascular ultrasonography or optical coherence tomography can be used to better evaluate the vessel.⁴⁵ Although optical coherence tomography has greater spatial resolution, it is more costly and is not as widely used as intravascular ultrasonography in the clinical setting

Managing SCAD. Although conservative management and coronary artery bypass grafting have been shown to cause minimal in-hospital morbidity, percutaneous coronary intervention has been complicated by technical failure in up to 35% of patients in one series.⁴⁶

While there is no standardized way to manage these patients, experts currently recommend conservative management with standard therapies for acute coronary syndrome (Figure 4). Although antithrombotic agents can decrease thrombus burden, they must be used with caution, because they also increase the risk of bleeding into the false lumen.

If patients experience recurrent or ongoing ischemia despite conservative management, then revascularization should be considered. Optical coherence tomography or intravascular ultrasonography is recommended to ensure proper stent alignment and positioning.

Coronary artery bypass grafting could be considered in preference to percutaneous coronary intervention, given that the former appears to be safer,⁴⁶ although this requires further investigation. Some studies have cautioned against using fibrinolytic therapy, based on anecdotal evidence that it may further propagate the dissection,⁴⁵ although this therapy has been used in other case studies.⁴⁶

While mortality rates are relatively low (95% survival at 2 years),⁴⁵ the estimated risk of recurrent SCAD at 10 years is approximately 30%.⁴⁶

Image courtesy of Dr. Heather Gornik

Associated with fibromuscular dysplasia. Of note, a sizeable number of patients with SCAD have been found to have fibromuscular dysplasia. This is a nonatherosclerotic, noninflammatory vascular condition that can affect any vascular bed in the body, although there is a predilection for the renal and carotid arteries (Figure 5).⁴⁷ Fibromuscular dysplasia also disproportionately affects women and appears to be a concomitant condition in the majority of patients with SCAD.⁴⁷ Imaging of the carotid and renal arteries of patients with SCAD has revealed a number of cases of fibromuscular dysplasia.^46,48 This noted association will likely allow for ongoing research to better understand the pathophysiology of these two conditions.