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CVS Caremark formulary change freezes out apixaban
Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.
The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.
In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.
PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.
Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.
“The underlying driver is cost,” he told this news organization.
Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.
“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”
Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.
“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”
Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.
The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.
The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.
Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”
The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.
Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.
In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.
During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”
The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.
“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.
In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.
The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.
PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.
One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”
A version of this article first appeared on Medscape.com.
Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.
The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.
In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.
PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.
Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.
“The underlying driver is cost,” he told this news organization.
Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.
“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”
Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.
“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”
Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.
The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.
The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.
Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”
The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.
Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.
In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.
During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”
The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.
“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.
In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.
The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.
PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.
One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”
A version of this article first appeared on Medscape.com.
Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.
The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.
In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.
PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.
Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.
“The underlying driver is cost,” he told this news organization.
Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.
“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”
Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.
“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”
Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.
The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.
The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.
Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”
The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.
Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.
In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.
During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”
The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.
“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.
In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.
The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.
PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.
One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”
A version of this article first appeared on Medscape.com.
What does a pig-to-human heart transplant mean for medicine?
Scientific achievements usually raise big new questions, and the remarkable surgery that took place on Jan. 7, when Maryland resident David Bennett was transplanted with a genetically modified heart from a pig, has been no different.
The 57-year-old with end-stage heart failure had been repeatedly turned down for a standard transplant and was judged a poor candidate for a ventricular assist device. Now his new heart is beating soundly and apparently accepted by his immune system as Mr. Bennett, his physicians at the University of Maryland where the procedure took place, and indeed the world set out on a journey with far more unknowns than knowns.
“I think even just a couple of years ago, people felt that xenotransplantation for the heart and other organs was still a long way off. And it seems like it’s started to move very quickly,” Larry A. Allen, MD, University of Colorado, Aurora, said in an interview.
Demand for donor hearts far outstrips supply, and despite advances in the development of ventricular assist pumps and artificial hearts, “there are still significant limitations to them in terms of clotting, stroke, and infection. We’ve seen the use of those devices plateau,” Dr. Allen said. “So, the concept of a nonhuman source of organs is exciting and very much in need, if people can get it to work.”
“I really credit the surgeons at the University of Maryland for courageous clinical work and a brilliant scientific innovation,” Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, said in an interview. “But it’s always in the implementation that we have to hold our breath.” Heart xenotransplantation is an old idea that “has never before been successful,” he said. And standard heart transplantation has set a high bar, with a 1-year survival of about 90% and low 1-year risk for rejection. Whether the new procedure can meet that standard is unknown, as is its potential for complications, such as chronic rejection or cancers due to long-term immunosuppression. Those are “major questions requiring more time and careful follow-up.”
‘Still a nascent technology’
“This is an exciting and courageous step forward in heart transplantation, and kudos to the team at the University of Maryland,” said Mandeep R. Mehra, MD, Brigham and Woman’s Hospital, Boston. But “there are many challenges here.”
The procedure’s 10 gene modifications were reportedly aimed at preventing hyperacute rejection of the heart and its excessive growth after transplantation, and making the organ less immunogenic, Dr. Mehra said in an interview. But even if those goals are met, could the same changes potentially impede the heart’s adaptation to human physiology, such as during ambulation or stress?
That kind of adaptation may become important. For example, Dr. Mehra observed, normally a pig heart “provides flow in a four-footed configuration, and pig temperature is inherently higher than humans by several degrees, so it will be functioning in a relatively hypothermic environment.”
Transplantation remains the gold standard for patients with advanced heart failure despite modern medical and device therapy, Dr. Allen agreed. But “if we can raise pig hearts that provide the organ, and it can be implanted with a surgery that’s been done for 50 years, and rejection can be managed with gene editing and tailored immunosuppression, then it’s not hard to think about this very rapidly replacing a lot of what we do in the advanced heart failure and transplantation world.”
Certainly, it would be a major advance if the gene editing technique successfully improves the heart’s immunologic compatibility, Dr. Yancy noted. But do we have enough genomic knowledge to select gene deletions and insertions in the safest way for a successful outcome? “We have to appreciate that this is still a nascent technology, and we should be careful that there might be consequences that we haven’t anticipated.”
For example, he said, the xenotransplantation and gene-modifying techniques should be explored in a range of patients, including older and younger people, women and men, and people of different ethnicities and races.
“There may be some differences based on ancestry, based on gender, based on aging, that will influence the way in which these engineered donor hearts are experienced clinically,” Dr. Yancy said.
The xenotransplantation technique’s potential impact on health equity should also be considered, as it “almost assuredly will be a very expensive technology that will be utilized in a very select population,” he noted. “We need to have a really wide lens to think about all of the potential ramifications.”
‘This field needs to evolve’
Dr. Mehra also flagged the procedure’s potential cost should it become mainstream. Perhaps that would promote dialogue on how to primarily use it “after legitimately exhausting all available options, such as total artificial heart support.”
It might also teach the field to take greater advantage of the many donated hearts discarded as suboptimal. “The general usage rate for offered organs is around a third,” despite opportunities to expand use of those that are “less than perfect,” Dr. Mehra said. “I think that the field will grow with the community focusing on reduced discards of current available heart organs, and not necessarily grow because of the availability of ‘xeno-organs.’ ”
“This field needs to evolve because we’re actively transplanting patients today. But in my mind, the real future is to have such a sufficient understanding of the biology of left ventricular dysfunction that transplantation is a rare event,” Dr. Yancy proposed.
“I’m not certain that heart transplantation per se is the endgame. I think the avoidance of transplantation is the real endgame,” he said. “This may be controversial, but my vision of the future is not one where we have a supply of animals that we can use for transplantation. My vision of the future is that heart transplantation becomes obsolete.”
A version of this article first appeared on Medscape.com.
Scientific achievements usually raise big new questions, and the remarkable surgery that took place on Jan. 7, when Maryland resident David Bennett was transplanted with a genetically modified heart from a pig, has been no different.
The 57-year-old with end-stage heart failure had been repeatedly turned down for a standard transplant and was judged a poor candidate for a ventricular assist device. Now his new heart is beating soundly and apparently accepted by his immune system as Mr. Bennett, his physicians at the University of Maryland where the procedure took place, and indeed the world set out on a journey with far more unknowns than knowns.
“I think even just a couple of years ago, people felt that xenotransplantation for the heart and other organs was still a long way off. And it seems like it’s started to move very quickly,” Larry A. Allen, MD, University of Colorado, Aurora, said in an interview.
Demand for donor hearts far outstrips supply, and despite advances in the development of ventricular assist pumps and artificial hearts, “there are still significant limitations to them in terms of clotting, stroke, and infection. We’ve seen the use of those devices plateau,” Dr. Allen said. “So, the concept of a nonhuman source of organs is exciting and very much in need, if people can get it to work.”
“I really credit the surgeons at the University of Maryland for courageous clinical work and a brilliant scientific innovation,” Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, said in an interview. “But it’s always in the implementation that we have to hold our breath.” Heart xenotransplantation is an old idea that “has never before been successful,” he said. And standard heart transplantation has set a high bar, with a 1-year survival of about 90% and low 1-year risk for rejection. Whether the new procedure can meet that standard is unknown, as is its potential for complications, such as chronic rejection or cancers due to long-term immunosuppression. Those are “major questions requiring more time and careful follow-up.”
‘Still a nascent technology’
“This is an exciting and courageous step forward in heart transplantation, and kudos to the team at the University of Maryland,” said Mandeep R. Mehra, MD, Brigham and Woman’s Hospital, Boston. But “there are many challenges here.”
The procedure’s 10 gene modifications were reportedly aimed at preventing hyperacute rejection of the heart and its excessive growth after transplantation, and making the organ less immunogenic, Dr. Mehra said in an interview. But even if those goals are met, could the same changes potentially impede the heart’s adaptation to human physiology, such as during ambulation or stress?
That kind of adaptation may become important. For example, Dr. Mehra observed, normally a pig heart “provides flow in a four-footed configuration, and pig temperature is inherently higher than humans by several degrees, so it will be functioning in a relatively hypothermic environment.”
Transplantation remains the gold standard for patients with advanced heart failure despite modern medical and device therapy, Dr. Allen agreed. But “if we can raise pig hearts that provide the organ, and it can be implanted with a surgery that’s been done for 50 years, and rejection can be managed with gene editing and tailored immunosuppression, then it’s not hard to think about this very rapidly replacing a lot of what we do in the advanced heart failure and transplantation world.”
Certainly, it would be a major advance if the gene editing technique successfully improves the heart’s immunologic compatibility, Dr. Yancy noted. But do we have enough genomic knowledge to select gene deletions and insertions in the safest way for a successful outcome? “We have to appreciate that this is still a nascent technology, and we should be careful that there might be consequences that we haven’t anticipated.”
For example, he said, the xenotransplantation and gene-modifying techniques should be explored in a range of patients, including older and younger people, women and men, and people of different ethnicities and races.
“There may be some differences based on ancestry, based on gender, based on aging, that will influence the way in which these engineered donor hearts are experienced clinically,” Dr. Yancy said.
The xenotransplantation technique’s potential impact on health equity should also be considered, as it “almost assuredly will be a very expensive technology that will be utilized in a very select population,” he noted. “We need to have a really wide lens to think about all of the potential ramifications.”
‘This field needs to evolve’
Dr. Mehra also flagged the procedure’s potential cost should it become mainstream. Perhaps that would promote dialogue on how to primarily use it “after legitimately exhausting all available options, such as total artificial heart support.”
It might also teach the field to take greater advantage of the many donated hearts discarded as suboptimal. “The general usage rate for offered organs is around a third,” despite opportunities to expand use of those that are “less than perfect,” Dr. Mehra said. “I think that the field will grow with the community focusing on reduced discards of current available heart organs, and not necessarily grow because of the availability of ‘xeno-organs.’ ”
“This field needs to evolve because we’re actively transplanting patients today. But in my mind, the real future is to have such a sufficient understanding of the biology of left ventricular dysfunction that transplantation is a rare event,” Dr. Yancy proposed.
“I’m not certain that heart transplantation per se is the endgame. I think the avoidance of transplantation is the real endgame,” he said. “This may be controversial, but my vision of the future is not one where we have a supply of animals that we can use for transplantation. My vision of the future is that heart transplantation becomes obsolete.”
A version of this article first appeared on Medscape.com.
Scientific achievements usually raise big new questions, and the remarkable surgery that took place on Jan. 7, when Maryland resident David Bennett was transplanted with a genetically modified heart from a pig, has been no different.
The 57-year-old with end-stage heart failure had been repeatedly turned down for a standard transplant and was judged a poor candidate for a ventricular assist device. Now his new heart is beating soundly and apparently accepted by his immune system as Mr. Bennett, his physicians at the University of Maryland where the procedure took place, and indeed the world set out on a journey with far more unknowns than knowns.
“I think even just a couple of years ago, people felt that xenotransplantation for the heart and other organs was still a long way off. And it seems like it’s started to move very quickly,” Larry A. Allen, MD, University of Colorado, Aurora, said in an interview.
Demand for donor hearts far outstrips supply, and despite advances in the development of ventricular assist pumps and artificial hearts, “there are still significant limitations to them in terms of clotting, stroke, and infection. We’ve seen the use of those devices plateau,” Dr. Allen said. “So, the concept of a nonhuman source of organs is exciting and very much in need, if people can get it to work.”
“I really credit the surgeons at the University of Maryland for courageous clinical work and a brilliant scientific innovation,” Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, said in an interview. “But it’s always in the implementation that we have to hold our breath.” Heart xenotransplantation is an old idea that “has never before been successful,” he said. And standard heart transplantation has set a high bar, with a 1-year survival of about 90% and low 1-year risk for rejection. Whether the new procedure can meet that standard is unknown, as is its potential for complications, such as chronic rejection or cancers due to long-term immunosuppression. Those are “major questions requiring more time and careful follow-up.”
‘Still a nascent technology’
“This is an exciting and courageous step forward in heart transplantation, and kudos to the team at the University of Maryland,” said Mandeep R. Mehra, MD, Brigham and Woman’s Hospital, Boston. But “there are many challenges here.”
The procedure’s 10 gene modifications were reportedly aimed at preventing hyperacute rejection of the heart and its excessive growth after transplantation, and making the organ less immunogenic, Dr. Mehra said in an interview. But even if those goals are met, could the same changes potentially impede the heart’s adaptation to human physiology, such as during ambulation or stress?
That kind of adaptation may become important. For example, Dr. Mehra observed, normally a pig heart “provides flow in a four-footed configuration, and pig temperature is inherently higher than humans by several degrees, so it will be functioning in a relatively hypothermic environment.”
Transplantation remains the gold standard for patients with advanced heart failure despite modern medical and device therapy, Dr. Allen agreed. But “if we can raise pig hearts that provide the organ, and it can be implanted with a surgery that’s been done for 50 years, and rejection can be managed with gene editing and tailored immunosuppression, then it’s not hard to think about this very rapidly replacing a lot of what we do in the advanced heart failure and transplantation world.”
Certainly, it would be a major advance if the gene editing technique successfully improves the heart’s immunologic compatibility, Dr. Yancy noted. But do we have enough genomic knowledge to select gene deletions and insertions in the safest way for a successful outcome? “We have to appreciate that this is still a nascent technology, and we should be careful that there might be consequences that we haven’t anticipated.”
For example, he said, the xenotransplantation and gene-modifying techniques should be explored in a range of patients, including older and younger people, women and men, and people of different ethnicities and races.
“There may be some differences based on ancestry, based on gender, based on aging, that will influence the way in which these engineered donor hearts are experienced clinically,” Dr. Yancy said.
The xenotransplantation technique’s potential impact on health equity should also be considered, as it “almost assuredly will be a very expensive technology that will be utilized in a very select population,” he noted. “We need to have a really wide lens to think about all of the potential ramifications.”
‘This field needs to evolve’
Dr. Mehra also flagged the procedure’s potential cost should it become mainstream. Perhaps that would promote dialogue on how to primarily use it “after legitimately exhausting all available options, such as total artificial heart support.”
It might also teach the field to take greater advantage of the many donated hearts discarded as suboptimal. “The general usage rate for offered organs is around a third,” despite opportunities to expand use of those that are “less than perfect,” Dr. Mehra said. “I think that the field will grow with the community focusing on reduced discards of current available heart organs, and not necessarily grow because of the availability of ‘xeno-organs.’ ”
“This field needs to evolve because we’re actively transplanting patients today. But in my mind, the real future is to have such a sufficient understanding of the biology of left ventricular dysfunction that transplantation is a rare event,” Dr. Yancy proposed.
“I’m not certain that heart transplantation per se is the endgame. I think the avoidance of transplantation is the real endgame,” he said. “This may be controversial, but my vision of the future is not one where we have a supply of animals that we can use for transplantation. My vision of the future is that heart transplantation becomes obsolete.”
A version of this article first appeared on Medscape.com.
Pig heart successfully transplanted to man
A genetically modified pig heart has been successfully transplanted into a 57-year-old man who had no other treatment options but is “doing well” 3 days after the procedure, officials at the University of Maryland Medical Center (UMMC), Baltimore, announced Jan. 10.
“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” they said.
Three genes associated with antibody-mediated rejection had been knocked out in the pig supplying the transplanted heart, and six human genes associated with immune acceptance of the organ had been inserted into the pig’s genome, notes a UMMC press release.
“Lastly, one additional gene in the pig was knocked out to prevent excessive growth of the pig heart tissue, which totaled 10 unique gene edits made in the donor pig,” the release states.
The patient, Maryland resident David Bennett, had required mechanical circulatory support to stay alive but was rejected for standard heart transplantation at UMMC and other centers. He was ineligible for an implanted ventricular assist device due to ventricular arrhythmias.
Mr. Bennett “is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits,” the announcement says.
“We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future,” notes a quote from Bartley P. Griffith, MD, the UMMC surgeon who performed the procedure.
The pig supplying the heart was provided to the center by Revivicor (Blacksburg, Virginia), a regenerative medicine company. An experimental antirejection medication (Kiniksa Pharmaceuticals; Lexington, Massachusetts) was also used, in addition to standard immunosuppressants.
A version of this article first appeared on Medscape.com.
A genetically modified pig heart has been successfully transplanted into a 57-year-old man who had no other treatment options but is “doing well” 3 days after the procedure, officials at the University of Maryland Medical Center (UMMC), Baltimore, announced Jan. 10.
“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” they said.
Three genes associated with antibody-mediated rejection had been knocked out in the pig supplying the transplanted heart, and six human genes associated with immune acceptance of the organ had been inserted into the pig’s genome, notes a UMMC press release.
“Lastly, one additional gene in the pig was knocked out to prevent excessive growth of the pig heart tissue, which totaled 10 unique gene edits made in the donor pig,” the release states.
The patient, Maryland resident David Bennett, had required mechanical circulatory support to stay alive but was rejected for standard heart transplantation at UMMC and other centers. He was ineligible for an implanted ventricular assist device due to ventricular arrhythmias.
Mr. Bennett “is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits,” the announcement says.
“We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future,” notes a quote from Bartley P. Griffith, MD, the UMMC surgeon who performed the procedure.
The pig supplying the heart was provided to the center by Revivicor (Blacksburg, Virginia), a regenerative medicine company. An experimental antirejection medication (Kiniksa Pharmaceuticals; Lexington, Massachusetts) was also used, in addition to standard immunosuppressants.
A version of this article first appeared on Medscape.com.
A genetically modified pig heart has been successfully transplanted into a 57-year-old man who had no other treatment options but is “doing well” 3 days after the procedure, officials at the University of Maryland Medical Center (UMMC), Baltimore, announced Jan. 10.
“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” they said.
Three genes associated with antibody-mediated rejection had been knocked out in the pig supplying the transplanted heart, and six human genes associated with immune acceptance of the organ had been inserted into the pig’s genome, notes a UMMC press release.
“Lastly, one additional gene in the pig was knocked out to prevent excessive growth of the pig heart tissue, which totaled 10 unique gene edits made in the donor pig,” the release states.
The patient, Maryland resident David Bennett, had required mechanical circulatory support to stay alive but was rejected for standard heart transplantation at UMMC and other centers. He was ineligible for an implanted ventricular assist device due to ventricular arrhythmias.
Mr. Bennett “is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits,” the announcement says.
“We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future,” notes a quote from Bartley P. Griffith, MD, the UMMC surgeon who performed the procedure.
The pig supplying the heart was provided to the center by Revivicor (Blacksburg, Virginia), a regenerative medicine company. An experimental antirejection medication (Kiniksa Pharmaceuticals; Lexington, Massachusetts) was also used, in addition to standard immunosuppressants.
A version of this article first appeared on Medscape.com.
A high-risk medical device didn’t meet federal standards. The government paid millions for more
In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.
But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.
Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.
Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.
If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.
“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”
The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.
The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.
CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.
The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.
CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.
A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”
In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.
In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.
The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.
In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.
Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.
Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.
“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.
Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.
Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.
Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.
“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.
This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.
In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.
But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.
Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.
Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.
If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.
“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”
The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.
The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.
CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.
The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.
CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.
A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”
In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.
In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.
The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.
In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.
Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.
Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.
“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.
Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.
Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.
Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.
“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.
This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.
In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.
But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.
Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.
Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.
If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.
“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”
The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.
The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.
CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.
The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.
CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.
A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”
In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.
In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.
The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.
In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.
Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.
Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.
“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.
Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.
Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.
Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.
“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.
This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.
Bleeding after reperfusion contributes to cardiac injury in MI
The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.
This observation is leading to new approaches to limiting infarct size and treating MI.
“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.
“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”
It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.
“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”
Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.
The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.
“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.
“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”
The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).
The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.
They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.
They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.
Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.
In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.
“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.
“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.
Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.
He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.”
Final frontier
In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.
But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.
However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”
This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.
A version of this article first appeared on Medscape.com.
The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.
This observation is leading to new approaches to limiting infarct size and treating MI.
“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.
“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”
It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.
“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”
Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.
The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.
“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.
“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”
The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).
The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.
They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.
They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.
Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.
In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.
“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.
“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.
Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.
He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.”
Final frontier
In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.
But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.
However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”
This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.
A version of this article first appeared on Medscape.com.
The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.
This observation is leading to new approaches to limiting infarct size and treating MI.
“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.
“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”
It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.
“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”
Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.
The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.
“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.
“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”
The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).
The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.
They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.
They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.
Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.
In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.
“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.
“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.
Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.
He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.”
Final frontier
In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.
But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.
However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”
This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.
A version of this article first appeared on Medscape.com.
Similar 10-year survival after CABG, PCI in heavy calcification
Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.
However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).
These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.
“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.
“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested. 
In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”
Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).
The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.
Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
Consider factors beyond coronary anatomy
The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.
“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.
The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.
Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”
“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”
This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.
More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.
“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”
“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.
“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
Worse clinical outcomes
Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.
To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.
Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.
The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.
At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.
After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).
In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).
The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.
Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.
The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.
In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.
SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.
A version of this article first appeared on Medscape.com.
Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.
However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).
These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.
“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.
“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.
In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”
Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).
The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.
Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
Consider factors beyond coronary anatomy
The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.
“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.
The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.
Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”
“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”
This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.
More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.
“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”
“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.
“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
Worse clinical outcomes
Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.
To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.
Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.
The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.
At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.
After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).
In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).
The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.
Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.
The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.
In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.
SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.
A version of this article first appeared on Medscape.com.
Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.
However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).
These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.
“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.
“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.
In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”
Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).
The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.
Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
Consider factors beyond coronary anatomy
The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.
“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.
The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.
Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”
“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”
This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.
More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.
“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”
“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.
“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
Worse clinical outcomes
Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.
To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.
Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.
The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.
At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.
After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).
In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).
The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.
Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.
The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.
In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.
SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.
A version of this article first appeared on Medscape.com.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
Surgical groups push back against new revascularization guidelines
The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.
The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.
The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.
“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”
The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.
The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.
At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
CABG and PCI treated as equal
AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.
“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”
The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.
In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.
“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.
“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
Class I for radial conduit
AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.
“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
Unequal footing
In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.
“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”
EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”
The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.
“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.
In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.
“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”
Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.
Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.
A version of this article first appeared on Medscape.com.
The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.
The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.
The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.
“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”
The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.
The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.
At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
CABG and PCI treated as equal
AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.
“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”
The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.
In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.
“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.
“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
Class I for radial conduit
AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.
“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
Unequal footing
In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.
“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”
EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”
The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.
“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.
In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.
“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”
Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.
Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.
A version of this article first appeared on Medscape.com.
The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.
The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.
The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.
“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”
The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.
The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.
At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
CABG and PCI treated as equal
AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.
“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”
The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.
In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.
“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.
“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
Class I for radial conduit
AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.
“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
Unequal footing
In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.
“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”
EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”
The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.
“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.
In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.
“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”
Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.
Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.
A version of this article first appeared on Medscape.com.
Who benefits most from device PFO closure after a stroke?
It has been well established that device closure has, on average, prevented stroke recurrence in people who’ve had patent foramen ovale–associated stroke, but a meta-analysis has drilled down into clinical trials to advance a potentially practice-changing principle: that, while device closure shows an overall benefit, not all patients derive a benefit and some may actually be harmed by the procedure.
What’s more, the researchers developed a scoring system that helps determine which patients are likely to benefit from device closure.
“What was unknown was how to treat individual patients because the decision to close the patent foramen ovale (PFO) is still preference sensitive because the risk of a recurrent stroke is low, and most of the strokes that recur are not terribly severe,” lead study author David M. Kent, MD, MS, said in an interview.
“On top of this,” he said, “it was still suspected that some of the PFOs, even in trials of well-selected patients, may not be causally related to stroke; the stroke may still have another occult cause, such as paroxysmal atrial fibrillation or aortic arch atheroma.” Dr. Kent is a professor of medicine at Tufts University in Boston and director of the Predictive Analytics and Comparative Effectiveness Center there.
The meta-analysis, conducted by the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium, analyzed data from six randomized clinical trials that compared device closure and medical therapy to medical therapy alone in 3,740 patients who had PFO-associated stroke from 2000 to 2017. It was published in JAMA.
Overall, the rate of recurrent ischemic stroke was less than half that in patients who had device closure, compared with those who were on medical therapy: 0.47% (n = 39 of 1,889) vs. 1.09% (n = 82 of 1,851).
The researchers also applied two tools designed to calculate the probability of recurrent stroke in individual patients: Risk of Paradoxical Embolism (RoPE), an index that assigns a score of 0-10 to stratify cryptogenic stroke patients with PFO by the likelihood that the stroke was associated with their PFO; and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system, which integrates the RoPE score with physiological and anatomical features – namely, the size of the PFO shunt and the presence of an atrial septal aneurysm.
“We came up with a way to more accurately identify those patients who are likely to get the most benefit from PFO closure based on mathematic modeling that estimates an individual’s probability that the PFO is causally related to the stroke,” Dr. Kent said.
Multivariate analysis determines risk
The study used a multivariate classification system that Dr. Kent had been developing to perform subgroup analyses of the clinical trials. It assigned patients to three different risk groups based on the likelihood that the PFO was causally related to their stroke: PASCAL categories of unlikely, possible, and probable.
The PASCAL unlikely group had a risk of stroke recurrence in the first 2 years of 3.4% (95% confidence interval, 1.1%-5.7%) if they were on medical therapy, and 4.1% (95% CI, 1.7%-6.4%) if they had device closure. In the PASCAL possible group, those risks were 3.6% (95% CI, 2.4%-4.9%) and 1.5% (95% CI, 0.7-2.3%), respectively. For the probable group, device closure represents “a near perfect therapy” with a 90% risk reduction, Dr. Kent said. “Moreover,” he said, “adverse events of device closure, such as atrial fibrillation, appear to be concentrated in those patients who fall into the unlikely classification, who appear to get no benefit.”
The ideal patient for device closure is age 60 years or younger and without vascular risk factors such as hypertension, diabetes, a history of smoking, or a prior stroke, but has high-risk PFO features such as a large shunt or atrial septal aneurysm, Dr. Kent said.
“We think these findings should be practice changing now,” Dr. Kent said.
Faisal M. Merchant, MD, director of cardiac electrophysiology at Emory Healthcare in Atlanta, concurred with that statement. “This is in my mind probably as good as any data we’re going to get on this,” he said in an interview. “The results support what’s been a general gestalt in the clinical world, but [also] really provide an evidence base on how to make decisions.”
He noted that guidelines, including those of the American Academy of Neurology, recommend medical therapy or device closure to prevent recurrent stroke in people who’ve had PFO-associated ischemic stroke. “But they hedge a bit,” he said of the guidelines. “We haven’t had data that’s as robust as this. I think this really solidifies those recommendations.”
He also credited the “unique” study design to extract findings from clinical trials and apply them to personalized medicine. “Clinical trial results give you an average treatment effect of the patients included, but who are ones who really benefit? Who are the ones that don’t benefit? Who are the ones who are harmed?” Dr. Merchant said. “It’s rare that you can parse out this nicely between the people who both benefit and are less likely to be harmed and the people who don’t benefit and are more likely to be harmed.”
The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Kent disclosed relationships with PCORI, W.L. Gore and the Canadian Stroke Consortium. Dr. Merchant has no relevant disclosures.
It has been well established that device closure has, on average, prevented stroke recurrence in people who’ve had patent foramen ovale–associated stroke, but a meta-analysis has drilled down into clinical trials to advance a potentially practice-changing principle: that, while device closure shows an overall benefit, not all patients derive a benefit and some may actually be harmed by the procedure.
What’s more, the researchers developed a scoring system that helps determine which patients are likely to benefit from device closure.
“What was unknown was how to treat individual patients because the decision to close the patent foramen ovale (PFO) is still preference sensitive because the risk of a recurrent stroke is low, and most of the strokes that recur are not terribly severe,” lead study author David M. Kent, MD, MS, said in an interview.
“On top of this,” he said, “it was still suspected that some of the PFOs, even in trials of well-selected patients, may not be causally related to stroke; the stroke may still have another occult cause, such as paroxysmal atrial fibrillation or aortic arch atheroma.” Dr. Kent is a professor of medicine at Tufts University in Boston and director of the Predictive Analytics and Comparative Effectiveness Center there.
The meta-analysis, conducted by the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium, analyzed data from six randomized clinical trials that compared device closure and medical therapy to medical therapy alone in 3,740 patients who had PFO-associated stroke from 2000 to 2017. It was published in JAMA.
Overall, the rate of recurrent ischemic stroke was less than half that in patients who had device closure, compared with those who were on medical therapy: 0.47% (n = 39 of 1,889) vs. 1.09% (n = 82 of 1,851).
The researchers also applied two tools designed to calculate the probability of recurrent stroke in individual patients: Risk of Paradoxical Embolism (RoPE), an index that assigns a score of 0-10 to stratify cryptogenic stroke patients with PFO by the likelihood that the stroke was associated with their PFO; and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system, which integrates the RoPE score with physiological and anatomical features – namely, the size of the PFO shunt and the presence of an atrial septal aneurysm.
“We came up with a way to more accurately identify those patients who are likely to get the most benefit from PFO closure based on mathematic modeling that estimates an individual’s probability that the PFO is causally related to the stroke,” Dr. Kent said.
Multivariate analysis determines risk
The study used a multivariate classification system that Dr. Kent had been developing to perform subgroup analyses of the clinical trials. It assigned patients to three different risk groups based on the likelihood that the PFO was causally related to their stroke: PASCAL categories of unlikely, possible, and probable.
The PASCAL unlikely group had a risk of stroke recurrence in the first 2 years of 3.4% (95% confidence interval, 1.1%-5.7%) if they were on medical therapy, and 4.1% (95% CI, 1.7%-6.4%) if they had device closure. In the PASCAL possible group, those risks were 3.6% (95% CI, 2.4%-4.9%) and 1.5% (95% CI, 0.7-2.3%), respectively. For the probable group, device closure represents “a near perfect therapy” with a 90% risk reduction, Dr. Kent said. “Moreover,” he said, “adverse events of device closure, such as atrial fibrillation, appear to be concentrated in those patients who fall into the unlikely classification, who appear to get no benefit.”
The ideal patient for device closure is age 60 years or younger and without vascular risk factors such as hypertension, diabetes, a history of smoking, or a prior stroke, but has high-risk PFO features such as a large shunt or atrial septal aneurysm, Dr. Kent said.
“We think these findings should be practice changing now,” Dr. Kent said.
Faisal M. Merchant, MD, director of cardiac electrophysiology at Emory Healthcare in Atlanta, concurred with that statement. “This is in my mind probably as good as any data we’re going to get on this,” he said in an interview. “The results support what’s been a general gestalt in the clinical world, but [also] really provide an evidence base on how to make decisions.”
He noted that guidelines, including those of the American Academy of Neurology, recommend medical therapy or device closure to prevent recurrent stroke in people who’ve had PFO-associated ischemic stroke. “But they hedge a bit,” he said of the guidelines. “We haven’t had data that’s as robust as this. I think this really solidifies those recommendations.”
He also credited the “unique” study design to extract findings from clinical trials and apply them to personalized medicine. “Clinical trial results give you an average treatment effect of the patients included, but who are ones who really benefit? Who are the ones that don’t benefit? Who are the ones who are harmed?” Dr. Merchant said. “It’s rare that you can parse out this nicely between the people who both benefit and are less likely to be harmed and the people who don’t benefit and are more likely to be harmed.”
The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Kent disclosed relationships with PCORI, W.L. Gore and the Canadian Stroke Consortium. Dr. Merchant has no relevant disclosures.
It has been well established that device closure has, on average, prevented stroke recurrence in people who’ve had patent foramen ovale–associated stroke, but a meta-analysis has drilled down into clinical trials to advance a potentially practice-changing principle: that, while device closure shows an overall benefit, not all patients derive a benefit and some may actually be harmed by the procedure.
What’s more, the researchers developed a scoring system that helps determine which patients are likely to benefit from device closure.
“What was unknown was how to treat individual patients because the decision to close the patent foramen ovale (PFO) is still preference sensitive because the risk of a recurrent stroke is low, and most of the strokes that recur are not terribly severe,” lead study author David M. Kent, MD, MS, said in an interview.
“On top of this,” he said, “it was still suspected that some of the PFOs, even in trials of well-selected patients, may not be causally related to stroke; the stroke may still have another occult cause, such as paroxysmal atrial fibrillation or aortic arch atheroma.” Dr. Kent is a professor of medicine at Tufts University in Boston and director of the Predictive Analytics and Comparative Effectiveness Center there.
The meta-analysis, conducted by the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium, analyzed data from six randomized clinical trials that compared device closure and medical therapy to medical therapy alone in 3,740 patients who had PFO-associated stroke from 2000 to 2017. It was published in JAMA.
Overall, the rate of recurrent ischemic stroke was less than half that in patients who had device closure, compared with those who were on medical therapy: 0.47% (n = 39 of 1,889) vs. 1.09% (n = 82 of 1,851).
The researchers also applied two tools designed to calculate the probability of recurrent stroke in individual patients: Risk of Paradoxical Embolism (RoPE), an index that assigns a score of 0-10 to stratify cryptogenic stroke patients with PFO by the likelihood that the stroke was associated with their PFO; and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system, which integrates the RoPE score with physiological and anatomical features – namely, the size of the PFO shunt and the presence of an atrial septal aneurysm.
“We came up with a way to more accurately identify those patients who are likely to get the most benefit from PFO closure based on mathematic modeling that estimates an individual’s probability that the PFO is causally related to the stroke,” Dr. Kent said.
Multivariate analysis determines risk
The study used a multivariate classification system that Dr. Kent had been developing to perform subgroup analyses of the clinical trials. It assigned patients to three different risk groups based on the likelihood that the PFO was causally related to their stroke: PASCAL categories of unlikely, possible, and probable.
The PASCAL unlikely group had a risk of stroke recurrence in the first 2 years of 3.4% (95% confidence interval, 1.1%-5.7%) if they were on medical therapy, and 4.1% (95% CI, 1.7%-6.4%) if they had device closure. In the PASCAL possible group, those risks were 3.6% (95% CI, 2.4%-4.9%) and 1.5% (95% CI, 0.7-2.3%), respectively. For the probable group, device closure represents “a near perfect therapy” with a 90% risk reduction, Dr. Kent said. “Moreover,” he said, “adverse events of device closure, such as atrial fibrillation, appear to be concentrated in those patients who fall into the unlikely classification, who appear to get no benefit.”
The ideal patient for device closure is age 60 years or younger and without vascular risk factors such as hypertension, diabetes, a history of smoking, or a prior stroke, but has high-risk PFO features such as a large shunt or atrial septal aneurysm, Dr. Kent said.
“We think these findings should be practice changing now,” Dr. Kent said.
Faisal M. Merchant, MD, director of cardiac electrophysiology at Emory Healthcare in Atlanta, concurred with that statement. “This is in my mind probably as good as any data we’re going to get on this,” he said in an interview. “The results support what’s been a general gestalt in the clinical world, but [also] really provide an evidence base on how to make decisions.”
He noted that guidelines, including those of the American Academy of Neurology, recommend medical therapy or device closure to prevent recurrent stroke in people who’ve had PFO-associated ischemic stroke. “But they hedge a bit,” he said of the guidelines. “We haven’t had data that’s as robust as this. I think this really solidifies those recommendations.”
He also credited the “unique” study design to extract findings from clinical trials and apply them to personalized medicine. “Clinical trial results give you an average treatment effect of the patients included, but who are ones who really benefit? Who are the ones that don’t benefit? Who are the ones who are harmed?” Dr. Merchant said. “It’s rare that you can parse out this nicely between the people who both benefit and are less likely to be harmed and the people who don’t benefit and are more likely to be harmed.”
The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Kent disclosed relationships with PCORI, W.L. Gore and the Canadian Stroke Consortium. Dr. Merchant has no relevant disclosures.
FROM JAMA
Class I recall of percutaneous thrombolytic device
Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.
The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.
The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.
“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.
“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.
“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.
To date, there have been seven complaints and no injuries or deaths reported for this device.
The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.
Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.
Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].
Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.
Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.
The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.
The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.
“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.
“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.
“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.
To date, there have been seven complaints and no injuries or deaths reported for this device.
The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.
Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.
Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].
Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.
Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.
The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.
The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.
“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.
“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.
“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.
To date, there have been seven complaints and no injuries or deaths reported for this device.
The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.
Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.
Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].
Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.
Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Valentin Fuster: ‘Atherosclerosis starts in the femoral artery’
Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.
Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.
Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”
We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.
Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.
“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.
His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.
“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.
But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.
“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.
Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.
In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.
The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.
In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.
“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
Education
Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.
“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.
“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.
A version of this article first appeared on Medscape.com.
Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.
Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.
Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”
We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.
Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.
“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.
His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.
“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.
But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.
“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.
Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.
In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.
The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.
In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.
“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
Education
Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.
“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.
“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.
A version of this article first appeared on Medscape.com.
Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.
Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.
Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”
We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.
Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.
“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.
His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.
“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.
But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.
“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.
Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.
In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.
The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.
In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.
“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
Education
Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.
“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.
“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.
A version of this article first appeared on Medscape.com.