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The Official Newspaper of the American Association for Thoracic Surgery
AATS Week 2017 Call for Abstracts & Videos
AATS welcomes you to submit your abstracts and videos to AATS Week 2017.
AATS Mitral Conclave
April 27-28, 2017
New York, NY
AATS Centennial
April 29-May 3, 2017
Boston, MA
Submission Deadlines:
AATS Centennial: Monday, October 17, 2016 @ 11.59 pm EDT
Mitral Conclave: Sunday, January 8, 2017 @ 11.59 pm EST
AATS welcomes you to submit your abstracts and videos to AATS Week 2017.
AATS Mitral Conclave
April 27-28, 2017
New York, NY
AATS Centennial
April 29-May 3, 2017
Boston, MA
Submission Deadlines:
AATS Centennial: Monday, October 17, 2016 @ 11.59 pm EDT
Mitral Conclave: Sunday, January 8, 2017 @ 11.59 pm EST
AATS welcomes you to submit your abstracts and videos to AATS Week 2017.
AATS Mitral Conclave
April 27-28, 2017
New York, NY
AATS Centennial
April 29-May 3, 2017
Boston, MA
Submission Deadlines:
AATS Centennial: Monday, October 17, 2016 @ 11.59 pm EDT
Mitral Conclave: Sunday, January 8, 2017 @ 11.59 pm EST
“Honoring Our Mentor” Fellowships Open for Submission
The AATS Graham Foundation is calling for submission for its “Honoring Our Mentors” fellowships.
This series is named after prominent CT surgeons who have demonstrated longstanding leadership and dedication over the course of their careers in both their clinical practices and commitment to training the future generation.
Lawrence H. Cohn Clinical Scholar Program
Allows young cardiac surgeons who are in their final year of their residency or have recently completed their residency to obtain advanced experience with valvular surgery or care.
Deadline: December 1, 2016
Denton A. Cooley Fellowship
New! Provides a deserving CT surgeon resident or young postgraduate surgeon the opportunity to enrich his/her education during four weeks of study at the Texas Heart Institute and Baylor St. Luke’s Medical.
Deadline: December 1, 2016
Marc de Leval Fellowship
Offers four to six weeks of congenital heart surgery training at an international center for a North American surgeon.
Deadline: December 1, 2016
F. Griffith Pearson Fellowship
Surgeons who have finished their residency/fellowship in general thoracic surgery advance their clinical techniques at a North American host institute.
Deadline: December 1, 2016
The AATS Graham Foundation is calling for submission for its “Honoring Our Mentors” fellowships.
This series is named after prominent CT surgeons who have demonstrated longstanding leadership and dedication over the course of their careers in both their clinical practices and commitment to training the future generation.
Lawrence H. Cohn Clinical Scholar Program
Allows young cardiac surgeons who are in their final year of their residency or have recently completed their residency to obtain advanced experience with valvular surgery or care.
Deadline: December 1, 2016
Denton A. Cooley Fellowship
New! Provides a deserving CT surgeon resident or young postgraduate surgeon the opportunity to enrich his/her education during four weeks of study at the Texas Heart Institute and Baylor St. Luke’s Medical.
Deadline: December 1, 2016
Marc de Leval Fellowship
Offers four to six weeks of congenital heart surgery training at an international center for a North American surgeon.
Deadline: December 1, 2016
F. Griffith Pearson Fellowship
Surgeons who have finished their residency/fellowship in general thoracic surgery advance their clinical techniques at a North American host institute.
Deadline: December 1, 2016
The AATS Graham Foundation is calling for submission for its “Honoring Our Mentors” fellowships.
This series is named after prominent CT surgeons who have demonstrated longstanding leadership and dedication over the course of their careers in both their clinical practices and commitment to training the future generation.
Lawrence H. Cohn Clinical Scholar Program
Allows young cardiac surgeons who are in their final year of their residency or have recently completed their residency to obtain advanced experience with valvular surgery or care.
Deadline: December 1, 2016
Denton A. Cooley Fellowship
New! Provides a deserving CT surgeon resident or young postgraduate surgeon the opportunity to enrich his/her education during four weeks of study at the Texas Heart Institute and Baylor St. Luke’s Medical.
Deadline: December 1, 2016
Marc de Leval Fellowship
Offers four to six weeks of congenital heart surgery training at an international center for a North American surgeon.
Deadline: December 1, 2016
F. Griffith Pearson Fellowship
Surgeons who have finished their residency/fellowship in general thoracic surgery advance their clinical techniques at a North American host institute.
Deadline: December 1, 2016
Registration and Housing Now Open: AATS Clinical Trials Methods Course 2016
October 20-22, 2016
Hyatt Regency O’Hare
Chicago, IL
Program Directors
David H. Harpole, Jr.
Marco A. Zenati
This course is an intensive, interactive training program for cardiothoracic surgeons across all subspecialties. It will permit them to acquire the critical skills necessary for effective clinical trial design and implementation. The course is particularly suited for professionals who are planning to apply for clinical trial funding, allowing them to better understand the complex nature of preparing and submitting clinical trial proposals.
Invited faculty includes currently funded clinical trial leading investigators and experts in the field of biostatistics and health sciences research. The program will offer a process in which the clinical trial protocol development can be streamlined. Interactive features will include hands-on focus groups and mock study sessions.
Register Today! Space available for only 40 participants.
October 20-22, 2016
Hyatt Regency O’Hare
Chicago, IL
Program Directors
David H. Harpole, Jr.
Marco A. Zenati
This course is an intensive, interactive training program for cardiothoracic surgeons across all subspecialties. It will permit them to acquire the critical skills necessary for effective clinical trial design and implementation. The course is particularly suited for professionals who are planning to apply for clinical trial funding, allowing them to better understand the complex nature of preparing and submitting clinical trial proposals.
Invited faculty includes currently funded clinical trial leading investigators and experts in the field of biostatistics and health sciences research. The program will offer a process in which the clinical trial protocol development can be streamlined. Interactive features will include hands-on focus groups and mock study sessions.
Register Today! Space available for only 40 participants.
October 20-22, 2016
Hyatt Regency O’Hare
Chicago, IL
Program Directors
David H. Harpole, Jr.
Marco A. Zenati
This course is an intensive, interactive training program for cardiothoracic surgeons across all subspecialties. It will permit them to acquire the critical skills necessary for effective clinical trial design and implementation. The course is particularly suited for professionals who are planning to apply for clinical trial funding, allowing them to better understand the complex nature of preparing and submitting clinical trial proposals.
Invited faculty includes currently funded clinical trial leading investigators and experts in the field of biostatistics and health sciences research. The program will offer a process in which the clinical trial protocol development can be streamlined. Interactive features will include hands-on focus groups and mock study sessions.
Register Today! Space available for only 40 participants.
Invest in the Future
Every day, CT surgeons transform the lives of their patients around the world. Your support is essential to ensure the future of our specialty and continue advancing global innovation in CT surgery. Please make a gift to the Graham Foundation or renew your commitment. Together, we can promote our specialty not only for the next generation of surgeons, but also the patients they serve.
Learn more about individual and corporate/organizational giving opportunities.
Contact Development Office: 978-927-8330
Every day, CT surgeons transform the lives of their patients around the world. Your support is essential to ensure the future of our specialty and continue advancing global innovation in CT surgery. Please make a gift to the Graham Foundation or renew your commitment. Together, we can promote our specialty not only for the next generation of surgeons, but also the patients they serve.
Learn more about individual and corporate/organizational giving opportunities.
Contact Development Office: 978-927-8330
Every day, CT surgeons transform the lives of their patients around the world. Your support is essential to ensure the future of our specialty and continue advancing global innovation in CT surgery. Please make a gift to the Graham Foundation or renew your commitment. Together, we can promote our specialty not only for the next generation of surgeons, but also the patients they serve.
Learn more about individual and corporate/organizational giving opportunities.
Contact Development Office: 978-927-8330
ENSURE-AF trial supports edoxaban for electrical cardioversion
ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.
The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.
And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.
Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.
Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.
The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.
Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.
The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.
Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.
ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).
Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.
“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.
“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.
In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.
“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.
The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.
Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.
ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.
The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.
And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.
Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.
Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.
The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.
Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.
The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.
Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.
ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).
Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.
“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.
“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.
In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.
“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.
The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.
Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.
ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.
The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.
And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.
Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.
Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.
The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.
Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.
The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.
Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.
ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).
Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.
“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.
“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.
In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.
“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.
The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.
Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.
AT THE ESC CONGRESS 2016
Key clinical point: Edoxaban is a safe, effective, and convenient alternative to warfarin for anticoagulation in patients undergoing electrical cardioversion of atrial fibrillation.
Major finding: The composite endpoint of stroke, other systemic embolic events, MI, or cardiovascular death occurred in 0.5% of patients with atrial fibrillation assigned to edoxaban for pericardioversion anticoagulation and in 1.0% on enoxaparin bridging to warfarin.
Data source: A randomized prospective multinational trial of 2,199 patients scheduled for electrical cardioversion of their nonvalvular atrial fibrillation.
Disclosures: The ENSURE-AF trial was funded by Daiichi Sankyo. The presenter reported receiving research grants from and serving as a consultant to that company as well as other pharmaceutical and medical device manufacturers.
VIDEO: Functional noninvasive imaging cuts unnecessary angiography
ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.
Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.
This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.
Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).
“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.
The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.
MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.
“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.
CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.
Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.
His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.
[email protected]
On Twitter @mitchelzoler
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The results from CE-MARC2 very nicely showed that imaging-guided angiography is as safe as compulsory angiography in the highest-risk subgroup of the enrolled patients, those with a pretest probability of 61%-90% for having coronary artery disease. Findings from the economic analysis of this study that remains pending will be crucial for eventually recommending one strategy over the other in this setting.
 |
| Mitchel L. Zoler/Frontline Medical News Dr. Udo Sechtem |
The 12-month rate of the hardest clinical endpoints measured in this study, cardiovascular deaths and MIs, was very low in this study: 1.3% in the patients managed with NICE guidance, 1% in those who first underwent cardiovascular MR, and 0.8% in the patients who first underwent myocardial perfusion scintigraphy. Despite this low risk, the patients in each of the three arms of the study underwent roughly 500 test procedures.
We should therefore consider a totally different approach. Instead of immediately performing a noninvasive test or the tests called for by the NICE guidelines, what about no testing at all. Instead, patients would first undergo optimal preventive and symptomatic medical treatments. If patients failed this strategy they then could be considered for revascularization. I propose a study that would compare imaging-guided conditional angiography, as tested in CE-MARC2, with symptom-guided conditional angiography. Functional, noninvasive testing for all needs to be compared against optimal management and symptom driven interventions.
Udo Sechtem, Dr Med, is head of cardiology at the Robert-Bosch-Hospital in Stuttgart, Germany. He made these comments as the designated discussant for the study. He had no disclosures.
The results from CE-MARC2 very nicely showed that imaging-guided angiography is as safe as compulsory angiography in the highest-risk subgroup of the enrolled patients, those with a pretest probability of 61%-90% for having coronary artery disease. Findings from the economic analysis of this study that remains pending will be crucial for eventually recommending one strategy over the other in this setting.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Udo Sechtem |
The 12-month rate of the hardest clinical endpoints measured in this study, cardiovascular deaths and MIs, was very low in this study: 1.3% in the patients managed with NICE guidance, 1% in those who first underwent cardiovascular MR, and 0.8% in the patients who first underwent myocardial perfusion scintigraphy. Despite this low risk, the patients in each of the three arms of the study underwent roughly 500 test procedures.
We should therefore consider a totally different approach. Instead of immediately performing a noninvasive test or the tests called for by the NICE guidelines, what about no testing at all. Instead, patients would first undergo optimal preventive and symptomatic medical treatments. If patients failed this strategy they then could be considered for revascularization. I propose a study that would compare imaging-guided conditional angiography, as tested in CE-MARC2, with symptom-guided conditional angiography. Functional, noninvasive testing for all needs to be compared against optimal management and symptom driven interventions.
Udo Sechtem, Dr Med, is head of cardiology at the Robert-Bosch-Hospital in Stuttgart, Germany. He made these comments as the designated discussant for the study. He had no disclosures.
The results from CE-MARC2 very nicely showed that imaging-guided angiography is as safe as compulsory angiography in the highest-risk subgroup of the enrolled patients, those with a pretest probability of 61%-90% for having coronary artery disease. Findings from the economic analysis of this study that remains pending will be crucial for eventually recommending one strategy over the other in this setting.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Udo Sechtem |
The 12-month rate of the hardest clinical endpoints measured in this study, cardiovascular deaths and MIs, was very low in this study: 1.3% in the patients managed with NICE guidance, 1% in those who first underwent cardiovascular MR, and 0.8% in the patients who first underwent myocardial perfusion scintigraphy. Despite this low risk, the patients in each of the three arms of the study underwent roughly 500 test procedures.
We should therefore consider a totally different approach. Instead of immediately performing a noninvasive test or the tests called for by the NICE guidelines, what about no testing at all. Instead, patients would first undergo optimal preventive and symptomatic medical treatments. If patients failed this strategy they then could be considered for revascularization. I propose a study that would compare imaging-guided conditional angiography, as tested in CE-MARC2, with symptom-guided conditional angiography. Functional, noninvasive testing for all needs to be compared against optimal management and symptom driven interventions.
Udo Sechtem, Dr Med, is head of cardiology at the Robert-Bosch-Hospital in Stuttgart, Germany. He made these comments as the designated discussant for the study. He had no disclosures.
ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.
Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.
This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.
Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).
“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.
The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.
MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.
“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.
CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.
Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.
His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.
[email protected]
On Twitter @mitchelzoler
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.
Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.
This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.
Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).
“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.
The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.
MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.
“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.
CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.
Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.
His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.
[email protected]
On Twitter @mitchelzoler
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ESC CONGRESS 2016
Key clinical point: Screening patients with suspected angina via cardiovascular MR or myocardial perfusion imaging substantially reduced the rate of unnecessary angiography compared with the screening algorithm currently endorsed by British national guidelines.
Major finding: The unnecessary angiography rate was 29% with the guideline algorithm, 7.5% with cardiovascular MR, and 7.1% with myocardial perfusion scintigraphy.
Data source: CE MARC2, a multicenter, randomized trial with 1,202 patients.
Disclosures: Dr. Greenwood had no disclosures.
VIDEO: Moderate LDL, SBP reductions slash cardiovascular events 90% over time
ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.
Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.
If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.
Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.
If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.
Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.
If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ESC CONGRESS 2016
IPF Patient Registry will expand
The number of patients enrolled in the Idiopathic Pulmonary Fibrosis–Prospective Outcomes (IPF-PRO) Registry will be increased to 1,500, Boehringer Ingelheim Pharmaceuticals and the Duke Clinical Research Institute have announced.
The organizations plan to accomplish this goal by increasing the number of sites they use to gather IPF patient data, according to a statement; the patients enrolled in the registry will now come from 45 sites instead of 18 sites.
IPF-PRO, which was launched in June 2014, is the first multicenter longitudinal disease state registry in the United States focused specifically on IPF. It was designed for the purpose of studying the progression of IPF and the effectiveness of various treatment approaches for the disease. The registry includes a biorepository that stores blood samples that provide patient genetic material.
“In collecting data from a larger, more diverse group of patients ... this registry will allow us to better assess the impact of the disease over time on clinical and patient-centered outcomes,” said Scott M. Palmer, MD, director of pulmonary research at the Duke Clinical Research Institute, Durham, N.C., in the statement.
More information on the registry is available at clinicaltrials.gov/ct2/show/NCT01915511.
The number of patients enrolled in the Idiopathic Pulmonary Fibrosis–Prospective Outcomes (IPF-PRO) Registry will be increased to 1,500, Boehringer Ingelheim Pharmaceuticals and the Duke Clinical Research Institute have announced.
The organizations plan to accomplish this goal by increasing the number of sites they use to gather IPF patient data, according to a statement; the patients enrolled in the registry will now come from 45 sites instead of 18 sites.
IPF-PRO, which was launched in June 2014, is the first multicenter longitudinal disease state registry in the United States focused specifically on IPF. It was designed for the purpose of studying the progression of IPF and the effectiveness of various treatment approaches for the disease. The registry includes a biorepository that stores blood samples that provide patient genetic material.
“In collecting data from a larger, more diverse group of patients ... this registry will allow us to better assess the impact of the disease over time on clinical and patient-centered outcomes,” said Scott M. Palmer, MD, director of pulmonary research at the Duke Clinical Research Institute, Durham, N.C., in the statement.
More information on the registry is available at clinicaltrials.gov/ct2/show/NCT01915511.
The number of patients enrolled in the Idiopathic Pulmonary Fibrosis–Prospective Outcomes (IPF-PRO) Registry will be increased to 1,500, Boehringer Ingelheim Pharmaceuticals and the Duke Clinical Research Institute have announced.
The organizations plan to accomplish this goal by increasing the number of sites they use to gather IPF patient data, according to a statement; the patients enrolled in the registry will now come from 45 sites instead of 18 sites.
IPF-PRO, which was launched in June 2014, is the first multicenter longitudinal disease state registry in the United States focused specifically on IPF. It was designed for the purpose of studying the progression of IPF and the effectiveness of various treatment approaches for the disease. The registry includes a biorepository that stores blood samples that provide patient genetic material.
“In collecting data from a larger, more diverse group of patients ... this registry will allow us to better assess the impact of the disease over time on clinical and patient-centered outcomes,” said Scott M. Palmer, MD, director of pulmonary research at the Duke Clinical Research Institute, Durham, N.C., in the statement.
More information on the registry is available at clinicaltrials.gov/ct2/show/NCT01915511.
Inadequate diversity snags hypertrophic cardiomyopathy genetic linkages
The genetic tests used for more than a decade to identify patients or family members who carry genetic mutations linked to hypertrophic cardiomyopathy are seriously flawed.
The tests have been erroneously flagging people as genetically positive for hypertrophic cardiomyopathy (HC) when they actually carried benign genetic variants, according to a new reassessment of the genetic linkages by researchers using a more genetically diverse database. Five genetic variants now reclassified as benign were collectively responsible for flagging 74% of people flagged at genetic risk for HC in the more than 8,500 cases examined.
The results call into question any genetic diagnosis of HC made since genetic testing entered the mainstream in 2003, especially among African Americans who seem to have been disproportionately affected by these mislabeled genetic markers because of inadequate population diversity when the markers were first established.
In addition, the results more broadly cast a shadow over the full spectrum of genetic tests for disease-linked variants now in routine medical practice because of the possibility that other linkage determinations derived from an inadequately-representative reference population, reported Arjun K. Manrai, PhD, and his associates (N Engl J Med. 2016 Aug 18;375[7]:655-65). The researchers call the HC experience they document a “cautionary tale of broad relevance to genetic diagnosis.”
The findings “powerfully illustrate the importance of racial and genetic diversity” when running linkage studies aimed at validating genetic markers for widespread clinical use, Isaac S. Kohane, MD, senior author of the study, said in a written statement. “Racial and ethnic inclusiveness improves the validity and accuracy” of genetic tests, said Dr. Kohane, professor of biomedical informatics and pediatrics at Harvard Medical School in Boston.
“We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of the iceberg of a larger problem that transcends a single genetic disease,” Dr. Manrai, a biomedical informatics researcher at Harvard, said in the same statement. “Much genetic assessment today relies on historical links between a disorder and variant, sometimes decades old. We believe our findings illustrate the critical need to systematically reevaluate prior assertions about genetic variants,” Dr. Manrai added in an interview.
The two researchers and their associates reexamined the link between genetic variants and HC in three genetic databases that involved a total of more than 8,500 people. One database included 4,300 white Americans and 2,203 black Americans. A second database included genetic data from 1,092 people from 14 worldwide populations, and the third had genetic data from 938 people from 51 worldwide populations.
The analysis showed that although 94 distinct genetic variants that had previously been reported as associated with HC were confirmed as linked, just 5 met the study’s definition of a “high-frequency” variant with an allele frequent of more than 1%. These five variants together accounted for 74% of the overall total of linkages seen in these 8,533 people. Further analysis classified all five of these high-frequency genetic variants as benign with no discernible link to HC.
These five high-frequency variants occurred disproportionately higher among black Americans, and the consequences of this showed up in the patient records the researchers reviewed from one large U.S. genetic testing laboratory. They examined in detail HC genetic test results during 2004-2013 from 2,912 unrelated people. The records showed seven people had been labeled as carrying either a pathogenic or “presumed pathogenic” variant when in fact they had one of the five high-frequency variants now declared benign. Five of the seven mislabeled people were of African ancestry; the other two had unknown ancestry.
The researchers called for reevaluating known variants for all genetic diseases in more diverse populations and to immediately release the results of updated linkage assessments. This has the potential to meaningfully rewrite current gospel for many genetic variants and linkages.
“Our findings point to the value of patients staying in contact with their genetic counselors and physicians, even years after genetic testing,” Dr. Manrai said. Reassessments using more diverse populations will take time, he acknowledged, but tools are available to allow clinical geneticists to update old variants and apply new ones in real time, as soon as a new assessment completes.
Dr. Manrai and Dr. Kohane had no disclosures.
On Twitter @mitchelzoler
The genetic tests used for more than a decade to identify patients or family members who carry genetic mutations linked to hypertrophic cardiomyopathy are seriously flawed.
The tests have been erroneously flagging people as genetically positive for hypertrophic cardiomyopathy (HC) when they actually carried benign genetic variants, according to a new reassessment of the genetic linkages by researchers using a more genetically diverse database. Five genetic variants now reclassified as benign were collectively responsible for flagging 74% of people flagged at genetic risk for HC in the more than 8,500 cases examined.
The results call into question any genetic diagnosis of HC made since genetic testing entered the mainstream in 2003, especially among African Americans who seem to have been disproportionately affected by these mislabeled genetic markers because of inadequate population diversity when the markers were first established.
In addition, the results more broadly cast a shadow over the full spectrum of genetic tests for disease-linked variants now in routine medical practice because of the possibility that other linkage determinations derived from an inadequately-representative reference population, reported Arjun K. Manrai, PhD, and his associates (N Engl J Med. 2016 Aug 18;375[7]:655-65). The researchers call the HC experience they document a “cautionary tale of broad relevance to genetic diagnosis.”
The findings “powerfully illustrate the importance of racial and genetic diversity” when running linkage studies aimed at validating genetic markers for widespread clinical use, Isaac S. Kohane, MD, senior author of the study, said in a written statement. “Racial and ethnic inclusiveness improves the validity and accuracy” of genetic tests, said Dr. Kohane, professor of biomedical informatics and pediatrics at Harvard Medical School in Boston.
“We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of the iceberg of a larger problem that transcends a single genetic disease,” Dr. Manrai, a biomedical informatics researcher at Harvard, said in the same statement. “Much genetic assessment today relies on historical links between a disorder and variant, sometimes decades old. We believe our findings illustrate the critical need to systematically reevaluate prior assertions about genetic variants,” Dr. Manrai added in an interview.
The two researchers and their associates reexamined the link between genetic variants and HC in three genetic databases that involved a total of more than 8,500 people. One database included 4,300 white Americans and 2,203 black Americans. A second database included genetic data from 1,092 people from 14 worldwide populations, and the third had genetic data from 938 people from 51 worldwide populations.
The analysis showed that although 94 distinct genetic variants that had previously been reported as associated with HC were confirmed as linked, just 5 met the study’s definition of a “high-frequency” variant with an allele frequent of more than 1%. These five variants together accounted for 74% of the overall total of linkages seen in these 8,533 people. Further analysis classified all five of these high-frequency genetic variants as benign with no discernible link to HC.
These five high-frequency variants occurred disproportionately higher among black Americans, and the consequences of this showed up in the patient records the researchers reviewed from one large U.S. genetic testing laboratory. They examined in detail HC genetic test results during 2004-2013 from 2,912 unrelated people. The records showed seven people had been labeled as carrying either a pathogenic or “presumed pathogenic” variant when in fact they had one of the five high-frequency variants now declared benign. Five of the seven mislabeled people were of African ancestry; the other two had unknown ancestry.
The researchers called for reevaluating known variants for all genetic diseases in more diverse populations and to immediately release the results of updated linkage assessments. This has the potential to meaningfully rewrite current gospel for many genetic variants and linkages.
“Our findings point to the value of patients staying in contact with their genetic counselors and physicians, even years after genetic testing,” Dr. Manrai said. Reassessments using more diverse populations will take time, he acknowledged, but tools are available to allow clinical geneticists to update old variants and apply new ones in real time, as soon as a new assessment completes.
Dr. Manrai and Dr. Kohane had no disclosures.
On Twitter @mitchelzoler
The genetic tests used for more than a decade to identify patients or family members who carry genetic mutations linked to hypertrophic cardiomyopathy are seriously flawed.
The tests have been erroneously flagging people as genetically positive for hypertrophic cardiomyopathy (HC) when they actually carried benign genetic variants, according to a new reassessment of the genetic linkages by researchers using a more genetically diverse database. Five genetic variants now reclassified as benign were collectively responsible for flagging 74% of people flagged at genetic risk for HC in the more than 8,500 cases examined.
The results call into question any genetic diagnosis of HC made since genetic testing entered the mainstream in 2003, especially among African Americans who seem to have been disproportionately affected by these mislabeled genetic markers because of inadequate population diversity when the markers were first established.
In addition, the results more broadly cast a shadow over the full spectrum of genetic tests for disease-linked variants now in routine medical practice because of the possibility that other linkage determinations derived from an inadequately-representative reference population, reported Arjun K. Manrai, PhD, and his associates (N Engl J Med. 2016 Aug 18;375[7]:655-65). The researchers call the HC experience they document a “cautionary tale of broad relevance to genetic diagnosis.”
The findings “powerfully illustrate the importance of racial and genetic diversity” when running linkage studies aimed at validating genetic markers for widespread clinical use, Isaac S. Kohane, MD, senior author of the study, said in a written statement. “Racial and ethnic inclusiveness improves the validity and accuracy” of genetic tests, said Dr. Kohane, professor of biomedical informatics and pediatrics at Harvard Medical School in Boston.
“We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of the iceberg of a larger problem that transcends a single genetic disease,” Dr. Manrai, a biomedical informatics researcher at Harvard, said in the same statement. “Much genetic assessment today relies on historical links between a disorder and variant, sometimes decades old. We believe our findings illustrate the critical need to systematically reevaluate prior assertions about genetic variants,” Dr. Manrai added in an interview.
The two researchers and their associates reexamined the link between genetic variants and HC in three genetic databases that involved a total of more than 8,500 people. One database included 4,300 white Americans and 2,203 black Americans. A second database included genetic data from 1,092 people from 14 worldwide populations, and the third had genetic data from 938 people from 51 worldwide populations.
The analysis showed that although 94 distinct genetic variants that had previously been reported as associated with HC were confirmed as linked, just 5 met the study’s definition of a “high-frequency” variant with an allele frequent of more than 1%. These five variants together accounted for 74% of the overall total of linkages seen in these 8,533 people. Further analysis classified all five of these high-frequency genetic variants as benign with no discernible link to HC.
These five high-frequency variants occurred disproportionately higher among black Americans, and the consequences of this showed up in the patient records the researchers reviewed from one large U.S. genetic testing laboratory. They examined in detail HC genetic test results during 2004-2013 from 2,912 unrelated people. The records showed seven people had been labeled as carrying either a pathogenic or “presumed pathogenic” variant when in fact they had one of the five high-frequency variants now declared benign. Five of the seven mislabeled people were of African ancestry; the other two had unknown ancestry.
The researchers called for reevaluating known variants for all genetic diseases in more diverse populations and to immediately release the results of updated linkage assessments. This has the potential to meaningfully rewrite current gospel for many genetic variants and linkages.
“Our findings point to the value of patients staying in contact with their genetic counselors and physicians, even years after genetic testing,” Dr. Manrai said. Reassessments using more diverse populations will take time, he acknowledged, but tools are available to allow clinical geneticists to update old variants and apply new ones in real time, as soon as a new assessment completes.
Dr. Manrai and Dr. Kohane had no disclosures.
On Twitter @mitchelzoler
Key clinical point: Five high-frequency genetic variants that collectively had been linked to 74% of hypertrophic cardiomyopathy cases are actually benign with no detectable pathologic linkage.
Major finding: Inaccurate linkage data mislabeled seven people as having a hypertrophic cardiomyopathy–causing genetic variant.
Data source: Three genomic sequence databases that included 8,533 people and a genetic laboratory’s records for 2,912 clients.
Disclosures: Dr. Manrai and Dr. Kohane had no disclosures.
Multiarterial grafting survival exceeds conventional CABG, PCI
A large, 16-year single-center study of patients with multivessel disease has determined that multivessel coronary artery bypass grafting achieved longer survival than not only percutaneous coronary interventions, but also conventional coronary artery bypass grafting, researchers from the Mayo Clinic reported in the August issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2016;152:369-79).
Lead author Chaim Locker, MD, and his colleagues said the use of what they called MultiArt, for multivessel arterial grafting, also known as MAG, “must increase.”
The evolution of bare-metal and then drug-eluting stents may have favored percutaneous coronary interventions (PCI) over coronary artery bypass grafting (CABG), but, Dr. Locker and his coauthors said, “Evidence is accumulating that late outcome of surgical revascularization is improved when at least two arterial grafts are used.”
The study analyzed results of 12,615 patients who had either isolated primary CABG (6,667) or PCI (5,948) from 1993 to 2009. Among the CABG patients, 5,712 had the more conventional approach involving arterial grafts into the left internal thoracic artery/saphenous vein (ITA/SV) and 955 had MAG. Patients in the PCI group had three different procedures: balloon angioplasty (1,020), drug-eluting stent (1,686), or bare-metal stent (3,242). The study excluded patients who had revascularization procedures after a heart attack.
While the overall 15-year survival for patients with CABG was lower than it was for those who had PCI (36% vs. 46%), the survival for those who had MAG was significantly higher: 65% vs. 31% for those who had left ITA/SV revascularization. 8-year survival for the MAG subgroup was also significantly higher than all other subgroups: 87% vs. 69% for left ITA/SV, 75% for bare-metal stent, 73% for balloon angioplasty, and 70% for drug-eluting stent.
Propensity matching found similar survivability for balloon angioplasty and left ITA/SV when compared with MAG: 66% for MAG vs. 57% for the former; and 64% for MAG vs. 56% for the latter. The researchers also estimated the hazard ratio during the first 5 years of follow-up and found that those who had bare-metal stents had “significantly worse” survival, compared with MAG, but that survival evened out after that. Survival in the bare-metal stent group was similar to that of the left ITA/SV group, but “significantly worse” during the first 5 years for those who had balloon angioplasty.
Dr. Locker and his colleagues acknowledged that multiple randomized studies have compared CABG and PCI over the years, but they said that in most of those studies “the enrolled patients were highly selected and likely did not represent the broader population of patients with MVD [multivessel disease] undergoing revascularization.” With the exception of the SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) (N Engl J Med. 2009;360:961-72; Lancet. 2013;381:629-38), those studies did not report on the frequency of MAG within the study population. The Mayo study, on the other hand, included all treated patients, excluding those who had a previous heart attack.
However, MAG is used infrequently, Dr. Locker and his colleagues said. The average annual rate of MAG in their Mayo practice was 15.2%, higher than the 5% annual rate the Society of Thoracic Surgeons National Cardiac Surgery Database (J Thorac Cardiovasc Surg. 2012;143:273-81) reported, and higher than the 12% rate in Europe (Eur J Cardiothorac Surg. 2006;29: 486-91). The SYNTAX trial reported an annual MAG rate of 27.6% for all CABG cases.
“It seems clear that use of MultiArt should be more frequent in patients with MVD undergoing CABG,” Dr. Locker and his coauthors said. “MultiArt can be used in most patients with MVD, including diabetic patients and elderly patients, and this strategy will improve outcomes of surgical revascularization.”
Dr. Locker and his coauthors had no financial relationships to disclose.
One might wonder about the validity of another retrospective, single-center study comparing revascularization techniques, but the study by Dr. Locker and his colleagues is “compelling” for two reasons, Paul Kurlansky, MD, of Columbia University, New York, pointed out in his invited commentary (J Thorac Cardiovasc Surg. 2016;152:380-1).
 |
Dr. Paul Kurlansky |
Dr. Kurlansky noted the finding of equivalent survival at up to 8 years among propensity-matched patients who had left coronary artery bypass grafting with the use of a single internal thoracic artery with supplemental vein grafts (left ITA/SV) and those who received drug-eluting stents was “a bit more provocative” than some of the expected study results; and the reversal of the survival benefit of left ITA/SV, compared with both balloon angioplasty and bare-metal stents after 7 to 10 years was “more perturbing for the surgical community.”
This study underscores that increased use of multiple arterial grafting is essential to give patients the best revascularization option, even in the age of growing percutaneous interventions, Dr. Kurlansky said.
“Limitations notwithstanding, the message for the surgical community is clear – if we wish to have the opportunity to treat patients with advanced, multivessel coronary artery disease, we will need to more fully embrace a strategy of MAG,” he said.
Dr. Kurlansky had no financial relationships to disclose.
One might wonder about the validity of another retrospective, single-center study comparing revascularization techniques, but the study by Dr. Locker and his colleagues is “compelling” for two reasons, Paul Kurlansky, MD, of Columbia University, New York, pointed out in his invited commentary (J Thorac Cardiovasc Surg. 2016;152:380-1).
|
Dr. Paul Kurlansky |
Dr. Kurlansky noted the finding of equivalent survival at up to 8 years among propensity-matched patients who had left coronary artery bypass grafting with the use of a single internal thoracic artery with supplemental vein grafts (left ITA/SV) and those who received drug-eluting stents was “a bit more provocative” than some of the expected study results; and the reversal of the survival benefit of left ITA/SV, compared with both balloon angioplasty and bare-metal stents after 7 to 10 years was “more perturbing for the surgical community.”
This study underscores that increased use of multiple arterial grafting is essential to give patients the best revascularization option, even in the age of growing percutaneous interventions, Dr. Kurlansky said.
“Limitations notwithstanding, the message for the surgical community is clear – if we wish to have the opportunity to treat patients with advanced, multivessel coronary artery disease, we will need to more fully embrace a strategy of MAG,” he said.
Dr. Kurlansky had no financial relationships to disclose.
One might wonder about the validity of another retrospective, single-center study comparing revascularization techniques, but the study by Dr. Locker and his colleagues is “compelling” for two reasons, Paul Kurlansky, MD, of Columbia University, New York, pointed out in his invited commentary (J Thorac Cardiovasc Surg. 2016;152:380-1).
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Dr. Paul Kurlansky |
Dr. Kurlansky noted the finding of equivalent survival at up to 8 years among propensity-matched patients who had left coronary artery bypass grafting with the use of a single internal thoracic artery with supplemental vein grafts (left ITA/SV) and those who received drug-eluting stents was “a bit more provocative” than some of the expected study results; and the reversal of the survival benefit of left ITA/SV, compared with both balloon angioplasty and bare-metal stents after 7 to 10 years was “more perturbing for the surgical community.”
This study underscores that increased use of multiple arterial grafting is essential to give patients the best revascularization option, even in the age of growing percutaneous interventions, Dr. Kurlansky said.
“Limitations notwithstanding, the message for the surgical community is clear – if we wish to have the opportunity to treat patients with advanced, multivessel coronary artery disease, we will need to more fully embrace a strategy of MAG,” he said.
Dr. Kurlansky had no financial relationships to disclose.
A large, 16-year single-center study of patients with multivessel disease has determined that multivessel coronary artery bypass grafting achieved longer survival than not only percutaneous coronary interventions, but also conventional coronary artery bypass grafting, researchers from the Mayo Clinic reported in the August issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2016;152:369-79).
Lead author Chaim Locker, MD, and his colleagues said the use of what they called MultiArt, for multivessel arterial grafting, also known as MAG, “must increase.”
The evolution of bare-metal and then drug-eluting stents may have favored percutaneous coronary interventions (PCI) over coronary artery bypass grafting (CABG), but, Dr. Locker and his coauthors said, “Evidence is accumulating that late outcome of surgical revascularization is improved when at least two arterial grafts are used.”
The study analyzed results of 12,615 patients who had either isolated primary CABG (6,667) or PCI (5,948) from 1993 to 2009. Among the CABG patients, 5,712 had the more conventional approach involving arterial grafts into the left internal thoracic artery/saphenous vein (ITA/SV) and 955 had MAG. Patients in the PCI group had three different procedures: balloon angioplasty (1,020), drug-eluting stent (1,686), or bare-metal stent (3,242). The study excluded patients who had revascularization procedures after a heart attack.
While the overall 15-year survival for patients with CABG was lower than it was for those who had PCI (36% vs. 46%), the survival for those who had MAG was significantly higher: 65% vs. 31% for those who had left ITA/SV revascularization. 8-year survival for the MAG subgroup was also significantly higher than all other subgroups: 87% vs. 69% for left ITA/SV, 75% for bare-metal stent, 73% for balloon angioplasty, and 70% for drug-eluting stent.
Propensity matching found similar survivability for balloon angioplasty and left ITA/SV when compared with MAG: 66% for MAG vs. 57% for the former; and 64% for MAG vs. 56% for the latter. The researchers also estimated the hazard ratio during the first 5 years of follow-up and found that those who had bare-metal stents had “significantly worse” survival, compared with MAG, but that survival evened out after that. Survival in the bare-metal stent group was similar to that of the left ITA/SV group, but “significantly worse” during the first 5 years for those who had balloon angioplasty.
Dr. Locker and his colleagues acknowledged that multiple randomized studies have compared CABG and PCI over the years, but they said that in most of those studies “the enrolled patients were highly selected and likely did not represent the broader population of patients with MVD [multivessel disease] undergoing revascularization.” With the exception of the SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) (N Engl J Med. 2009;360:961-72; Lancet. 2013;381:629-38), those studies did not report on the frequency of MAG within the study population. The Mayo study, on the other hand, included all treated patients, excluding those who had a previous heart attack.
However, MAG is used infrequently, Dr. Locker and his colleagues said. The average annual rate of MAG in their Mayo practice was 15.2%, higher than the 5% annual rate the Society of Thoracic Surgeons National Cardiac Surgery Database (J Thorac Cardiovasc Surg. 2012;143:273-81) reported, and higher than the 12% rate in Europe (Eur J Cardiothorac Surg. 2006;29: 486-91). The SYNTAX trial reported an annual MAG rate of 27.6% for all CABG cases.
“It seems clear that use of MultiArt should be more frequent in patients with MVD undergoing CABG,” Dr. Locker and his coauthors said. “MultiArt can be used in most patients with MVD, including diabetic patients and elderly patients, and this strategy will improve outcomes of surgical revascularization.”
Dr. Locker and his coauthors had no financial relationships to disclose.
A large, 16-year single-center study of patients with multivessel disease has determined that multivessel coronary artery bypass grafting achieved longer survival than not only percutaneous coronary interventions, but also conventional coronary artery bypass grafting, researchers from the Mayo Clinic reported in the August issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2016;152:369-79).
Lead author Chaim Locker, MD, and his colleagues said the use of what they called MultiArt, for multivessel arterial grafting, also known as MAG, “must increase.”
The evolution of bare-metal and then drug-eluting stents may have favored percutaneous coronary interventions (PCI) over coronary artery bypass grafting (CABG), but, Dr. Locker and his coauthors said, “Evidence is accumulating that late outcome of surgical revascularization is improved when at least two arterial grafts are used.”
The study analyzed results of 12,615 patients who had either isolated primary CABG (6,667) or PCI (5,948) from 1993 to 2009. Among the CABG patients, 5,712 had the more conventional approach involving arterial grafts into the left internal thoracic artery/saphenous vein (ITA/SV) and 955 had MAG. Patients in the PCI group had three different procedures: balloon angioplasty (1,020), drug-eluting stent (1,686), or bare-metal stent (3,242). The study excluded patients who had revascularization procedures after a heart attack.
While the overall 15-year survival for patients with CABG was lower than it was for those who had PCI (36% vs. 46%), the survival for those who had MAG was significantly higher: 65% vs. 31% for those who had left ITA/SV revascularization. 8-year survival for the MAG subgroup was also significantly higher than all other subgroups: 87% vs. 69% for left ITA/SV, 75% for bare-metal stent, 73% for balloon angioplasty, and 70% for drug-eluting stent.
Propensity matching found similar survivability for balloon angioplasty and left ITA/SV when compared with MAG: 66% for MAG vs. 57% for the former; and 64% for MAG vs. 56% for the latter. The researchers also estimated the hazard ratio during the first 5 years of follow-up and found that those who had bare-metal stents had “significantly worse” survival, compared with MAG, but that survival evened out after that. Survival in the bare-metal stent group was similar to that of the left ITA/SV group, but “significantly worse” during the first 5 years for those who had balloon angioplasty.
Dr. Locker and his colleagues acknowledged that multiple randomized studies have compared CABG and PCI over the years, but they said that in most of those studies “the enrolled patients were highly selected and likely did not represent the broader population of patients with MVD [multivessel disease] undergoing revascularization.” With the exception of the SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) (N Engl J Med. 2009;360:961-72; Lancet. 2013;381:629-38), those studies did not report on the frequency of MAG within the study population. The Mayo study, on the other hand, included all treated patients, excluding those who had a previous heart attack.
However, MAG is used infrequently, Dr. Locker and his colleagues said. The average annual rate of MAG in their Mayo practice was 15.2%, higher than the 5% annual rate the Society of Thoracic Surgeons National Cardiac Surgery Database (J Thorac Cardiovasc Surg. 2012;143:273-81) reported, and higher than the 12% rate in Europe (Eur J Cardiothorac Surg. 2006;29: 486-91). The SYNTAX trial reported an annual MAG rate of 27.6% for all CABG cases.
“It seems clear that use of MultiArt should be more frequent in patients with MVD undergoing CABG,” Dr. Locker and his coauthors said. “MultiArt can be used in most patients with MVD, including diabetic patients and elderly patients, and this strategy will improve outcomes of surgical revascularization.”
Dr. Locker and his coauthors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Cardiac surgeons should use multiple arterial coronary artery bypass grafting (MAG) more frequently because it achieves superior survival, compared with conventional bypass surgery or percutaneous coronary interventions.
Major finding: The overall 8-year survival of those who had MAG was 87% vs. 69% for conventional coronary bypass surgery and 70%-75% for percutaneous procedures.
Data source: Retrospective, single-institution study of 12,615 patients with multivessel disease who had revascularization procedures at the Mayo Clinic from 1993 to 2009.
Disclosures: Dr. Locker and his coauthors had no financial relationships to disclose.
