Interventional Cardiology & Surgery

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

Treatment with a novel myosin-inhibiting agent may improve symptoms and hemodynamics enough in patients with obstructive hypertrophic cardiomyopathy (OHCM) so that they can avoid or at least delay septal reduction therapy (SRT), suggests a randomized trial of modest size and duration.

Of 112 patients with OHCM who were sick enough while receiving standard medications to qualify for SRT, those assigned to take mavacamten (MyoKardia) instead of placebo were far less likely to still be eligible for SRT 16 weeks later.

In other words, their OHCM had improved enough during therapy with mavacamten such that SRT, either surgical septal myectomy or transcatheter alcohol septal ablation, could no longer be recommended per guidelines.

Mavacamten, which lessens myocardial contractility by selective inhibition of cardiac myosin, is the first agent tested in prospective trials to appear as a viable medical option in patients with severe, symptomatic OHCM, observed principal investigator Milind Y. Desai, MD, MBA, of the Cleveland Clinic.

“There’s clearly an unmet need for noninvasive therapies, medical therapies, that work in OHCM,” he said in an interview. Mavacamten “adds to the armamentarium” of OHCM management options and may give patients with symptoms despite conventional medications an alternative to SRT, which is considered definitive but has drawbacks.

The goal of SRT is to alleviate obstruction of the left ventricular outflow tract (LVOT), but surgical SRT requires a sternotomy, with all the risks and recovery time that entails. Catheter-based alcohol septal ablation is a less common alternative for some patients with suitable anatomy, Dr. Desai noted.

But those procedures “are not uniformly available, and even when  available, the outcomes are fairly heterogeneous,” he said. “The guidelines recommend that you should go to a center with a mortality rate of less than 1% with these procedures. Centers like that are very few across the world,” and procedural mortality can be much higher at centers with less SRT experience.

Dr. Desai presented the results of VALOR-HCM at the annual scientific sessions of the American College of Cardiology. Of the 56 patients assigned to mavacamten, 10 (17.9%) decided to undergo SRT by the end of the trial, or otherwise still met guideline-recommended criteria for receiving SRT, the primary endpoint. In comparison, 43 of the 56 patients (76.8%) in the control group (P < .0001) met that endpoint.

More patients receiving mavacamten improved by at least one New York Heart Association (NYHA) functional class during the trial’s 16 weeks: 63% versus 21% for those assigned to placebo. And 27% and 2%, respectively, improved by at least two NYHA classes, Dr. Desai said.

Guidelines recommend that SRT be reserved for patients in NYHA class III or IV heart failure with a resting or provoked LVOT gradient of at least 50 mm Hg.

Of note, Desai said, only two patients in each group elected to undergo SRT during the study. “The primary endpoint was driven by reduction in guideline eligibility for SRT, but 95% of patients in the study chose to continue with medical therapy.”

Speaking as a panelist after Dr. Desai’s presentation, Lynne W. Stevenson, MD, lauded the phase 3 trial’s “brave design,” which featured a highly unusual subjective primary endpoint and framed it as an advantage.

That the trial showed a significant mavacamten effect for that endpoint “answered, in one step, the question of what does this actually mean to the patient – which often takes much longer,” observed Dr. Stevenson, from Vanderbilt University, Nashville, Tenn.

Even so, she added, whether patients still qualified for SRT in the trial at least had to be supported by objective measures of LVOT gradient and NT-proBNP levels.

“My perspective is that of a cardiac surgeon who performs septal myectomies,” said John Cleveland, MD, University of Colorado at Denver, Aurora, who said he was impressed at how few patients receiving mavacamten went on to undergo SRT, while the rest were able to at least defer that decision.

Current recommendations are that patients who go to SRT “should be maximally medically treated and still symptomatic,” Dr. Cleveland observed at a press conference on VALOR-HCM. Should mavacamten be added to the list of agents to use before resorting to invasive therapy? “My answer would be yes,” he said, and patients who remain symptomatic even while receiving the myosin inhibitor and other medications should proceed to SRT.

The trial’s patients had documented OHCM, severe symptoms, and a resting or provoked LVOT gradient of at least 50 mm Hg despite maximally tolerated medications – which could include disopyramide, beta-blockers, and calcium channel blockers. About half the study population was female, and 89% were White. All had been referred for SRT.

Active therapy consisted of mavacamten initiated at 5 mg/day, with up-titrations at 8 and 12 weeks as tolerated, guided by echocardiographic left ventricular ejection fraction and LVOT gradient.  

Most secondary endpoints improved significantly in patients receiving the drug, compared with placebo. They included measures of quality of life, symptom status, ventricular function, natriuretic peptides, and troponin I.

The secondary outcomes are consistent with what was observed in the EXPLORER-HCM trial, which in 2020 suggested that mavacamten could improve measures of quality of life, NYHA functional class, LVOT gradient, peak VO2, and other metrics in patients with OHCM.

Dr. Desai said mavacamten was well tolerated. “There were two patients who had a transient drop in ejection fraction to less than 50%, so the drug was temporarily discontinued, but resumed at a lower dose and they were able to complete the study.”

Dr. Stevenson commented on the “pretty quick” up-titration of mavacamten dosages in a study lasting only 4 months, which could have been a concern given the drug’s limited track record and its mechanism of action targeting contractility. “Fortunately, no serious safety signals” were observed.

Dr. Desai emphasized that mavacamten up-titrations were strictly guided by regular echocardiographic monitoring and assessment of LVOT gradients, in addition to clinical responses. And that, he said, is likely how up-titrations should be carried out if mavacamten is approved for OHCM.

VALOR-HCM was supported by MyoKardia. Dr. Desai disclosed receiving honoraria or consulting fees from Caristo Diagnostics, Medtronic, and MyoKardia. Dr. Stevenson disclosed receiving honoraria or consulting fees from Novartis; serving on a data safety monitoring board for Livanova; and other relationships with Abbott Medical, Biotronik, Boston Scientific, Bristol-Myers Squibb, Endotronic, Gore Medical, and Johnson & Johnson. Dr. Cleveland had no disclosures.

A version of this article first appeared on Medscape.com.

Treatment with a novel myosin-inhibiting agent may improve symptoms and hemodynamics enough in patients with obstructive hypertrophic cardiomyopathy (OHCM) so that they can avoid or at least delay septal reduction therapy (SRT), suggests a randomized trial of modest size and duration.

Of 112 patients with OHCM who were sick enough while receiving standard medications to qualify for SRT, those assigned to take mavacamten (MyoKardia) instead of placebo were far less likely to still be eligible for SRT 16 weeks later.

In other words, their OHCM had improved enough during therapy with mavacamten such that SRT, either surgical septal myectomy or transcatheter alcohol septal ablation, could no longer be recommended per guidelines.

Mavacamten, which lessens myocardial contractility by selective inhibition of cardiac myosin, is the first agent tested in prospective trials to appear as a viable medical option in patients with severe, symptomatic OHCM, observed principal investigator Milind Y. Desai, MD, MBA, of the Cleveland Clinic.

“There’s clearly an unmet need for noninvasive therapies, medical therapies, that work in OHCM,” he said in an interview. Mavacamten “adds to the armamentarium” of OHCM management options and may give patients with symptoms despite conventional medications an alternative to SRT, which is considered definitive but has drawbacks.

The goal of SRT is to alleviate obstruction of the left ventricular outflow tract (LVOT), but surgical SRT requires a sternotomy, with all the risks and recovery time that entails. Catheter-based alcohol septal ablation is a less common alternative for some patients with suitable anatomy, Dr. Desai noted.

But those procedures “are not uniformly available, and even when  available, the outcomes are fairly heterogeneous,” he said. “The guidelines recommend that you should go to a center with a mortality rate of less than 1% with these procedures. Centers like that are very few across the world,” and procedural mortality can be much higher at centers with less SRT experience.

Dr. Desai presented the results of VALOR-HCM at the annual scientific sessions of the American College of Cardiology. Of the 56 patients assigned to mavacamten, 10 (17.9%) decided to undergo SRT by the end of the trial, or otherwise still met guideline-recommended criteria for receiving SRT, the primary endpoint. In comparison, 43 of the 56 patients (76.8%) in the control group (P < .0001) met that endpoint.

More patients receiving mavacamten improved by at least one New York Heart Association (NYHA) functional class during the trial’s 16 weeks: 63% versus 21% for those assigned to placebo. And 27% and 2%, respectively, improved by at least two NYHA classes, Dr. Desai said.

Guidelines recommend that SRT be reserved for patients in NYHA class III or IV heart failure with a resting or provoked LVOT gradient of at least 50 mm Hg.

Of note, Desai said, only two patients in each group elected to undergo SRT during the study. “The primary endpoint was driven by reduction in guideline eligibility for SRT, but 95% of patients in the study chose to continue with medical therapy.”

Speaking as a panelist after Dr. Desai’s presentation, Lynne W. Stevenson, MD, lauded the phase 3 trial’s “brave design,” which featured a highly unusual subjective primary endpoint and framed it as an advantage.

That the trial showed a significant mavacamten effect for that endpoint “answered, in one step, the question of what does this actually mean to the patient – which often takes much longer,” observed Dr. Stevenson, from Vanderbilt University, Nashville, Tenn.

Even so, she added, whether patients still qualified for SRT in the trial at least had to be supported by objective measures of LVOT gradient and NT-proBNP levels.

“My perspective is that of a cardiac surgeon who performs septal myectomies,” said John Cleveland, MD, University of Colorado at Denver, Aurora, who said he was impressed at how few patients receiving mavacamten went on to undergo SRT, while the rest were able to at least defer that decision.

Current recommendations are that patients who go to SRT “should be maximally medically treated and still symptomatic,” Dr. Cleveland observed at a press conference on VALOR-HCM. Should mavacamten be added to the list of agents to use before resorting to invasive therapy? “My answer would be yes,” he said, and patients who remain symptomatic even while receiving the myosin inhibitor and other medications should proceed to SRT.

The trial’s patients had documented OHCM, severe symptoms, and a resting or provoked LVOT gradient of at least 50 mm Hg despite maximally tolerated medications – which could include disopyramide, beta-blockers, and calcium channel blockers. About half the study population was female, and 89% were White. All had been referred for SRT.

Active therapy consisted of mavacamten initiated at 5 mg/day, with up-titrations at 8 and 12 weeks as tolerated, guided by echocardiographic left ventricular ejection fraction and LVOT gradient.  

Most secondary endpoints improved significantly in patients receiving the drug, compared with placebo. They included measures of quality of life, symptom status, ventricular function, natriuretic peptides, and troponin I.

The secondary outcomes are consistent with what was observed in the EXPLORER-HCM trial, which in 2020 suggested that mavacamten could improve measures of quality of life, NYHA functional class, LVOT gradient, peak VO2, and other metrics in patients with OHCM.

Dr. Desai said mavacamten was well tolerated. “There were two patients who had a transient drop in ejection fraction to less than 50%, so the drug was temporarily discontinued, but resumed at a lower dose and they were able to complete the study.”

Dr. Stevenson commented on the “pretty quick” up-titration of mavacamten dosages in a study lasting only 4 months, which could have been a concern given the drug’s limited track record and its mechanism of action targeting contractility. “Fortunately, no serious safety signals” were observed.

Dr. Desai emphasized that mavacamten up-titrations were strictly guided by regular echocardiographic monitoring and assessment of LVOT gradients, in addition to clinical responses. And that, he said, is likely how up-titrations should be carried out if mavacamten is approved for OHCM.

VALOR-HCM was supported by MyoKardia. Dr. Desai disclosed receiving honoraria or consulting fees from Caristo Diagnostics, Medtronic, and MyoKardia. Dr. Stevenson disclosed receiving honoraria or consulting fees from Novartis; serving on a data safety monitoring board for Livanova; and other relationships with Abbott Medical, Biotronik, Boston Scientific, Bristol-Myers Squibb, Endotronic, Gore Medical, and Johnson & Johnson. Dr. Cleveland had no disclosures.

A version of this article first appeared on Medscape.com.

Treatment with a novel myosin-inhibiting agent may improve symptoms and hemodynamics enough in patients with obstructive hypertrophic cardiomyopathy (OHCM) so that they can avoid or at least delay septal reduction therapy (SRT), suggests a randomized trial of modest size and duration.

Of 112 patients with OHCM who were sick enough while receiving standard medications to qualify for SRT, those assigned to take mavacamten (MyoKardia) instead of placebo were far less likely to still be eligible for SRT 16 weeks later.

In other words, their OHCM had improved enough during therapy with mavacamten such that SRT, either surgical septal myectomy or transcatheter alcohol septal ablation, could no longer be recommended per guidelines.

Mavacamten, which lessens myocardial contractility by selective inhibition of cardiac myosin, is the first agent tested in prospective trials to appear as a viable medical option in patients with severe, symptomatic OHCM, observed principal investigator Milind Y. Desai, MD, MBA, of the Cleveland Clinic.

“There’s clearly an unmet need for noninvasive therapies, medical therapies, that work in OHCM,” he said in an interview. Mavacamten “adds to the armamentarium” of OHCM management options and may give patients with symptoms despite conventional medications an alternative to SRT, which is considered definitive but has drawbacks.

The goal of SRT is to alleviate obstruction of the left ventricular outflow tract (LVOT), but surgical SRT requires a sternotomy, with all the risks and recovery time that entails. Catheter-based alcohol septal ablation is a less common alternative for some patients with suitable anatomy, Dr. Desai noted.

But those procedures “are not uniformly available, and even when  available, the outcomes are fairly heterogeneous,” he said. “The guidelines recommend that you should go to a center with a mortality rate of less than 1% with these procedures. Centers like that are very few across the world,” and procedural mortality can be much higher at centers with less SRT experience.

Dr. Desai presented the results of VALOR-HCM at the annual scientific sessions of the American College of Cardiology. Of the 56 patients assigned to mavacamten, 10 (17.9%) decided to undergo SRT by the end of the trial, or otherwise still met guideline-recommended criteria for receiving SRT, the primary endpoint. In comparison, 43 of the 56 patients (76.8%) in the control group (P < .0001) met that endpoint.

More patients receiving mavacamten improved by at least one New York Heart Association (NYHA) functional class during the trial’s 16 weeks: 63% versus 21% for those assigned to placebo. And 27% and 2%, respectively, improved by at least two NYHA classes, Dr. Desai said.

Guidelines recommend that SRT be reserved for patients in NYHA class III or IV heart failure with a resting or provoked LVOT gradient of at least 50 mm Hg.

Of note, Desai said, only two patients in each group elected to undergo SRT during the study. “The primary endpoint was driven by reduction in guideline eligibility for SRT, but 95% of patients in the study chose to continue with medical therapy.”

Speaking as a panelist after Dr. Desai’s presentation, Lynne W. Stevenson, MD, lauded the phase 3 trial’s “brave design,” which featured a highly unusual subjective primary endpoint and framed it as an advantage.

That the trial showed a significant mavacamten effect for that endpoint “answered, in one step, the question of what does this actually mean to the patient – which often takes much longer,” observed Dr. Stevenson, from Vanderbilt University, Nashville, Tenn.

Even so, she added, whether patients still qualified for SRT in the trial at least had to be supported by objective measures of LVOT gradient and NT-proBNP levels.

“My perspective is that of a cardiac surgeon who performs septal myectomies,” said John Cleveland, MD, University of Colorado at Denver, Aurora, who said he was impressed at how few patients receiving mavacamten went on to undergo SRT, while the rest were able to at least defer that decision.

Current recommendations are that patients who go to SRT “should be maximally medically treated and still symptomatic,” Dr. Cleveland observed at a press conference on VALOR-HCM. Should mavacamten be added to the list of agents to use before resorting to invasive therapy? “My answer would be yes,” he said, and patients who remain symptomatic even while receiving the myosin inhibitor and other medications should proceed to SRT.

The trial’s patients had documented OHCM, severe symptoms, and a resting or provoked LVOT gradient of at least 50 mm Hg despite maximally tolerated medications – which could include disopyramide, beta-blockers, and calcium channel blockers. About half the study population was female, and 89% were White. All had been referred for SRT.

Active therapy consisted of mavacamten initiated at 5 mg/day, with up-titrations at 8 and 12 weeks as tolerated, guided by echocardiographic left ventricular ejection fraction and LVOT gradient.  

Most secondary endpoints improved significantly in patients receiving the drug, compared with placebo. They included measures of quality of life, symptom status, ventricular function, natriuretic peptides, and troponin I.

The secondary outcomes are consistent with what was observed in the EXPLORER-HCM trial, which in 2020 suggested that mavacamten could improve measures of quality of life, NYHA functional class, LVOT gradient, peak VO2, and other metrics in patients with OHCM.

Dr. Desai said mavacamten was well tolerated. “There were two patients who had a transient drop in ejection fraction to less than 50%, so the drug was temporarily discontinued, but resumed at a lower dose and they were able to complete the study.”

Dr. Stevenson commented on the “pretty quick” up-titration of mavacamten dosages in a study lasting only 4 months, which could have been a concern given the drug’s limited track record and its mechanism of action targeting contractility. “Fortunately, no serious safety signals” were observed.

Dr. Desai emphasized that mavacamten up-titrations were strictly guided by regular echocardiographic monitoring and assessment of LVOT gradients, in addition to clinical responses. And that, he said, is likely how up-titrations should be carried out if mavacamten is approved for OHCM.

VALOR-HCM was supported by MyoKardia. Dr. Desai disclosed receiving honoraria or consulting fees from Caristo Diagnostics, Medtronic, and MyoKardia. Dr. Stevenson disclosed receiving honoraria or consulting fees from Novartis; serving on a data safety monitoring board for Livanova; and other relationships with Abbott Medical, Biotronik, Boston Scientific, Bristol-Myers Squibb, Endotronic, Gore Medical, and Johnson & Johnson. Dr. Cleveland had no disclosures.

A version of this article first appeared on Medscape.com.

A new subanalysis of the FAME 3 trial, which failed to show that percutaneous intervention (PCI) guided by fractional flow reserve (FFR) is noninferior to coronary artery bypass grafting (CABG) for treating three-vessel coronary artery disease, has associated PCI with early quality of life (QOL) advantages, according to findings presented at the annual scientific sessions of the American College of Cardiology.

Despite a modestly greater risk of major adverse cardiac events (MACE) at the end of 12 months’ follow-up among those treated with FFR-guided PCI, the greater QOL early after the procedure might be relevant to patients weighing these options, according to Frederik M. Zimmerman, MD, of Catharina Hospital in Eindhoven, the Netherlands.

“FFR-guided PCI results in a faster improvement in quality of life than CABG during the first year after revascularization, and it improved working status in patients younger than 65 years of age,” Dr. Zimmermann said.

The primary results of FAME 3 were presented at the 2021 Transcatheter Cardiovascular Therapeutics annual meeting by lead author William F. Fearon, MD, of Stanford (Calif.) University and published simultaneously in the New England Journal of Medicine.

Rather than confirming the hypothesis that FFR-guided PCI is comparable with CABG for the primary composite MACE outcome death from any cause, myocardial infarction, stroke, or revascularization, the incidence of MACE at 12 months was 10.6% in those randomized to PCI and 6.9% in the group assigned to CABG.

This translated into a hazard ratio for MACE of 1.5, signifying a 50% increase in risk for FFR-guided PCI relative to CABG for the primary outcome, a difference that negated the study definition of noninferiority (P = .35).

In this new health-related subanalysis, which was published simultaneously with his ACC presentation, the groups were compared over 12 months for QOL as measured with European Quality of Life–5 dimensions (EQ-5D) scale, angina as measured with the Canadian Cardiovascular Classification (CCC) system, and employment.

Outcomes data available in >85% of patients

Of the 1,500 patients enrolled and randomized in FAME 3 (757 to FFR-guided PCI and 743 to CABG), this health outcomes subanalysis was performed with complete data at 12 months from 89% of those in the PCI group and 88% of those in the CABG group.

Ultimately, the study did not show differences in any of these measures at the end of 12 months, but there were significant differences in QOL and employment at earlier time points. In particular, the significantly different (P < .001) trajectory for QOL improvement at 1 and 6 months favored FFR-guided PCI whether evaluated with the EQ-5D instrument or an EQ visual analog scale.

Rates of angina defined by as CCC class of at least 2 were low after revascularization in both arms of the study, negating any opportunity for differences, but patients aged younger than 65 years were almost twice as likely to have returned to full- or part-time work 1 month after revascularization (60.2% vs. 33.1%), and they remained at higher odds for working at 12 months (68.1% vs. 57.4%).

In patients aged older than 65 years, return-to-work rates did not differ significantly at any time point.

These results suggest potentially clinically meaningful early advantages for FFR-guided PCI, but some experts questioned the rationale for reporting positive secondary findings from a negative trial.

“This subanalysis is curious,” said Allen Jeremias, MD, director of interventional cardiology research, Saint Francis Hospital, Roslyn, N.Y. He pointed out that reporting these data is an anomaly.
 

Subanalyses uncommon in negative trials

“CABG was found to be better, so why look at QOL,” said Dr. Jeremias, who was an ACC-invited expert to discuss the results. However, he went on to say, “this could be an exception to the rule.”

The reason, according to Dr. Jeremias, is that the absolute difference at 12 months between FFR-guided PCI and CABG for the MACE events of greatest concern – death, MI, or stroke – was only about 2% greater in the FFR-guided PCI group (7.3% vs. 5.2%). The biggest contributor to the difference in MACE in FAME 3 at 12 months was the higher rate of repeat revascularization (5.9% vs. 3.9%).

Moreover, patients randomized to FFR-guided PCI had lower rates of many adverse events. This included risk of bleeding (1.6% vs. 3.8%; P = .009 as defined by type ≥3 Bleeding Academic Research Consortium , acute kidney injury (0.1% vs. 0.9%; P = .04), atrial fibrillation (2.4% vs. 14.1%; P < .001) and rehospitalization within 30 days (5.5% vs. 10.2%; P < .001).

In the context of a modest increase in risk of MACE and the lower rate of several important treatment-related adverse events, the QOL advantages identified in this subanalysis “might be a reasonable topic for patient-shared decision-making,” Dr. Jeremias suggested.
 

New data might inform patient decision-making

He granted the possibility that well-informed patients might accept the modestly increased risk of MACE for one or more of the outcomes, such as a higher likelihood of an early return to work, that favored FFR-guided PCI.

This is the point of this subanalysis, agreed Dr. Zimmermann.

“It is all about shared decision-making,” he said. Also emphasizing that the negative trial endpoint of FAME 3 “was driven largely by an increased risk of revascularization,” he believes that these new data might be a basis for discussions with patients weighing relative risks and benefits.

There are more data to come, according to Dr. Zimmermann, who said that follow-up of up to 5 years is planned. The 3-year data will be made available in 2023.

Dr. Zimmermann reported no potential conflicts of interest. Dr. Jeremias reported financial relationships with Abbott, ACIST, Boston Scientific, and Volcano. The investigator-initiated trial received research grants from Abbott Vascular and Medtronic.

A new subanalysis of the FAME 3 trial, which failed to show that percutaneous intervention (PCI) guided by fractional flow reserve (FFR) is noninferior to coronary artery bypass grafting (CABG) for treating three-vessel coronary artery disease, has associated PCI with early quality of life (QOL) advantages, according to findings presented at the annual scientific sessions of the American College of Cardiology.

Despite a modestly greater risk of major adverse cardiac events (MACE) at the end of 12 months’ follow-up among those treated with FFR-guided PCI, the greater QOL early after the procedure might be relevant to patients weighing these options, according to Frederik M. Zimmerman, MD, of Catharina Hospital in Eindhoven, the Netherlands.

“FFR-guided PCI results in a faster improvement in quality of life than CABG during the first year after revascularization, and it improved working status in patients younger than 65 years of age,” Dr. Zimmermann said.

The primary results of FAME 3 were presented at the 2021 Transcatheter Cardiovascular Therapeutics annual meeting by lead author William F. Fearon, MD, of Stanford (Calif.) University and published simultaneously in the New England Journal of Medicine.

Rather than confirming the hypothesis that FFR-guided PCI is comparable with CABG for the primary composite MACE outcome death from any cause, myocardial infarction, stroke, or revascularization, the incidence of MACE at 12 months was 10.6% in those randomized to PCI and 6.9% in the group assigned to CABG.

This translated into a hazard ratio for MACE of 1.5, signifying a 50% increase in risk for FFR-guided PCI relative to CABG for the primary outcome, a difference that negated the study definition of noninferiority (P = .35).

In this new health-related subanalysis, which was published simultaneously with his ACC presentation, the groups were compared over 12 months for QOL as measured with European Quality of Life–5 dimensions (EQ-5D) scale, angina as measured with the Canadian Cardiovascular Classification (CCC) system, and employment.

Outcomes data available in >85% of patients

Of the 1,500 patients enrolled and randomized in FAME 3 (757 to FFR-guided PCI and 743 to CABG), this health outcomes subanalysis was performed with complete data at 12 months from 89% of those in the PCI group and 88% of those in the CABG group.

Ultimately, the study did not show differences in any of these measures at the end of 12 months, but there were significant differences in QOL and employment at earlier time points. In particular, the significantly different (P < .001) trajectory for QOL improvement at 1 and 6 months favored FFR-guided PCI whether evaluated with the EQ-5D instrument or an EQ visual analog scale.

Rates of angina defined by as CCC class of at least 2 were low after revascularization in both arms of the study, negating any opportunity for differences, but patients aged younger than 65 years were almost twice as likely to have returned to full- or part-time work 1 month after revascularization (60.2% vs. 33.1%), and they remained at higher odds for working at 12 months (68.1% vs. 57.4%).

In patients aged older than 65 years, return-to-work rates did not differ significantly at any time point.

These results suggest potentially clinically meaningful early advantages for FFR-guided PCI, but some experts questioned the rationale for reporting positive secondary findings from a negative trial.

“This subanalysis is curious,” said Allen Jeremias, MD, director of interventional cardiology research, Saint Francis Hospital, Roslyn, N.Y. He pointed out that reporting these data is an anomaly.
 

Subanalyses uncommon in negative trials

“CABG was found to be better, so why look at QOL,” said Dr. Jeremias, who was an ACC-invited expert to discuss the results. However, he went on to say, “this could be an exception to the rule.”

The reason, according to Dr. Jeremias, is that the absolute difference at 12 months between FFR-guided PCI and CABG for the MACE events of greatest concern – death, MI, or stroke – was only about 2% greater in the FFR-guided PCI group (7.3% vs. 5.2%). The biggest contributor to the difference in MACE in FAME 3 at 12 months was the higher rate of repeat revascularization (5.9% vs. 3.9%).

Moreover, patients randomized to FFR-guided PCI had lower rates of many adverse events. This included risk of bleeding (1.6% vs. 3.8%; P = .009 as defined by type ≥3 Bleeding Academic Research Consortium , acute kidney injury (0.1% vs. 0.9%; P = .04), atrial fibrillation (2.4% vs. 14.1%; P < .001) and rehospitalization within 30 days (5.5% vs. 10.2%; P < .001).

In the context of a modest increase in risk of MACE and the lower rate of several important treatment-related adverse events, the QOL advantages identified in this subanalysis “might be a reasonable topic for patient-shared decision-making,” Dr. Jeremias suggested.
 

New data might inform patient decision-making

He granted the possibility that well-informed patients might accept the modestly increased risk of MACE for one or more of the outcomes, such as a higher likelihood of an early return to work, that favored FFR-guided PCI.

This is the point of this subanalysis, agreed Dr. Zimmermann.

“It is all about shared decision-making,” he said. Also emphasizing that the negative trial endpoint of FAME 3 “was driven largely by an increased risk of revascularization,” he believes that these new data might be a basis for discussions with patients weighing relative risks and benefits.

There are more data to come, according to Dr. Zimmermann, who said that follow-up of up to 5 years is planned. The 3-year data will be made available in 2023.

Dr. Zimmermann reported no potential conflicts of interest. Dr. Jeremias reported financial relationships with Abbott, ACIST, Boston Scientific, and Volcano. The investigator-initiated trial received research grants from Abbott Vascular and Medtronic.

A new subanalysis of the FAME 3 trial, which failed to show that percutaneous intervention (PCI) guided by fractional flow reserve (FFR) is noninferior to coronary artery bypass grafting (CABG) for treating three-vessel coronary artery disease, has associated PCI with early quality of life (QOL) advantages, according to findings presented at the annual scientific sessions of the American College of Cardiology.

Despite a modestly greater risk of major adverse cardiac events (MACE) at the end of 12 months’ follow-up among those treated with FFR-guided PCI, the greater QOL early after the procedure might be relevant to patients weighing these options, according to Frederik M. Zimmerman, MD, of Catharina Hospital in Eindhoven, the Netherlands.

“FFR-guided PCI results in a faster improvement in quality of life than CABG during the first year after revascularization, and it improved working status in patients younger than 65 years of age,” Dr. Zimmermann said.

The primary results of FAME 3 were presented at the 2021 Transcatheter Cardiovascular Therapeutics annual meeting by lead author William F. Fearon, MD, of Stanford (Calif.) University and published simultaneously in the New England Journal of Medicine.

Rather than confirming the hypothesis that FFR-guided PCI is comparable with CABG for the primary composite MACE outcome death from any cause, myocardial infarction, stroke, or revascularization, the incidence of MACE at 12 months was 10.6% in those randomized to PCI and 6.9% in the group assigned to CABG.

This translated into a hazard ratio for MACE of 1.5, signifying a 50% increase in risk for FFR-guided PCI relative to CABG for the primary outcome, a difference that negated the study definition of noninferiority (P = .35).

In this new health-related subanalysis, which was published simultaneously with his ACC presentation, the groups were compared over 12 months for QOL as measured with European Quality of Life–5 dimensions (EQ-5D) scale, angina as measured with the Canadian Cardiovascular Classification (CCC) system, and employment.

Outcomes data available in >85% of patients

Of the 1,500 patients enrolled and randomized in FAME 3 (757 to FFR-guided PCI and 743 to CABG), this health outcomes subanalysis was performed with complete data at 12 months from 89% of those in the PCI group and 88% of those in the CABG group.

Ultimately, the study did not show differences in any of these measures at the end of 12 months, but there were significant differences in QOL and employment at earlier time points. In particular, the significantly different (P < .001) trajectory for QOL improvement at 1 and 6 months favored FFR-guided PCI whether evaluated with the EQ-5D instrument or an EQ visual analog scale.

Rates of angina defined by as CCC class of at least 2 were low after revascularization in both arms of the study, negating any opportunity for differences, but patients aged younger than 65 years were almost twice as likely to have returned to full- or part-time work 1 month after revascularization (60.2% vs. 33.1%), and they remained at higher odds for working at 12 months (68.1% vs. 57.4%).

In patients aged older than 65 years, return-to-work rates did not differ significantly at any time point.

These results suggest potentially clinically meaningful early advantages for FFR-guided PCI, but some experts questioned the rationale for reporting positive secondary findings from a negative trial.

“This subanalysis is curious,” said Allen Jeremias, MD, director of interventional cardiology research, Saint Francis Hospital, Roslyn, N.Y. He pointed out that reporting these data is an anomaly.
 

Subanalyses uncommon in negative trials

“CABG was found to be better, so why look at QOL,” said Dr. Jeremias, who was an ACC-invited expert to discuss the results. However, he went on to say, “this could be an exception to the rule.”

The reason, according to Dr. Jeremias, is that the absolute difference at 12 months between FFR-guided PCI and CABG for the MACE events of greatest concern – death, MI, or stroke – was only about 2% greater in the FFR-guided PCI group (7.3% vs. 5.2%). The biggest contributor to the difference in MACE in FAME 3 at 12 months was the higher rate of repeat revascularization (5.9% vs. 3.9%).

Moreover, patients randomized to FFR-guided PCI had lower rates of many adverse events. This included risk of bleeding (1.6% vs. 3.8%; P = .009 as defined by type ≥3 Bleeding Academic Research Consortium , acute kidney injury (0.1% vs. 0.9%; P = .04), atrial fibrillation (2.4% vs. 14.1%; P < .001) and rehospitalization within 30 days (5.5% vs. 10.2%; P < .001).

In the context of a modest increase in risk of MACE and the lower rate of several important treatment-related adverse events, the QOL advantages identified in this subanalysis “might be a reasonable topic for patient-shared decision-making,” Dr. Jeremias suggested.
 

New data might inform patient decision-making

He granted the possibility that well-informed patients might accept the modestly increased risk of MACE for one or more of the outcomes, such as a higher likelihood of an early return to work, that favored FFR-guided PCI.

This is the point of this subanalysis, agreed Dr. Zimmermann.

“It is all about shared decision-making,” he said. Also emphasizing that the negative trial endpoint of FAME 3 “was driven largely by an increased risk of revascularization,” he believes that these new data might be a basis for discussions with patients weighing relative risks and benefits.

There are more data to come, according to Dr. Zimmermann, who said that follow-up of up to 5 years is planned. The 3-year data will be made available in 2023.

Dr. Zimmermann reported no potential conflicts of interest. Dr. Jeremias reported financial relationships with Abbott, ACIST, Boston Scientific, and Volcano. The investigator-initiated trial received research grants from Abbott Vascular and Medtronic.

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

A version of this article first appeared on Medscape.com.

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

A version of this article first appeared on Medscape.com.

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

A version of this article first appeared on Medscape.com.

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

A version of this article first appeared on Medscape.com.

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

A version of this article first appeared on Medscape.com.

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

A version of this article first appeared on Medscape.com.

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

A version of this article first appeared on Medscape.com.

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

A version of this article first appeared on Medscape.com.

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

A version of this article first appeared on Medscape.com.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

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.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

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.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

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.

The genetically altered pig’s heart “worked like a rock star, beautifully functioning,” the surgeon who performed the pioneering Jan. 7 xenotransplant procedure said in a press statement on the death of the patient, David Bennett Sr.

“He wasn’t able to overcome what turned out to be devastating – the debilitation from his previous period of heart failure, which was extreme,” said Bartley P. Griffith, MD, clinical director of the cardiac xenotransplantation program at the University of Maryland, Baltimore.

University of Maryland Medical Center

Representatives of the institution aren’t offering many details on the cause of Mr. Bennett’s death on March 8, 60 days after his operation, but said they will elaborate when their findings are formally published. But their comments seem to downplay the unique nature of the implanted heart itself as a culprit and instead implicate the patient’s diminished overall clinical condition and what grew into an ongoing battle with infections.

The 57-year-old Bennett, bedridden with end-stage heart failure, judged a poor candidate for a ventricular assist device, and on extracorporeal membrane oxygenation (ECMO), reportedly was offered the extraordinary surgery after being turned down for a conventional transplant at several major centers.

“Until day 45 or 50, he was doing very well,” Muhammad M. Mohiuddin, MD, the xenotransplantation program’s scientific director, observed in the statement. But infections soon took advantage of his hobbled immune system.

Given his “preexisting condition and how frail his body was,” Dr. Mohiuddin said, “we were having difficulty maintaining a balance between his immunosuppression and controlling his infection.” Mr. Bennett went into multiple organ failure and “I think that resulted in his passing away.”


 

Beyond wildest dreams

The surgeons confidently framed Mr. Bennett’s experience as a milestone for heart xenotransplantation. “The demonstration that it was possible, beyond the wildest dreams of most people in the field, even, at this point – that we were able to take a genetically engineered organ and watch it function flawlessly for 9 weeks – is pretty positive in terms of the potential of this therapy,” Dr. Griffith said.

But enough questions linger that others were more circumspect, even as they praised the accomplishment. “There’s no question that this is a historic event,” Mandeep R. Mehra, MD, of Harvard Medical School, and director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital, both in Boston, said in an interview.

Still, “I don’t think we should just conclude that it was the patient’s frailty or death from infection,” Dr. Mehra said. With so few details available, “I would be very careful in prematurely concluding that the problem did not reside with the heart but with the patient. We cannot be sure.”

For example, he noted, “6 to 8 weeks is right around the time when some cardiac complications, like accelerated forms of vasculopathy, could become evident.” Immune-mediated cardiac allograft vasculopathy is a common cause of heart transplant failure.

Or, “it could as easily have been the fact that immunosuppression was modified at 6 to 7 weeks in response to potential infection, which could have led to a cardiac compromise,” Dr. Mehra said. “We just don’t know.”

“It’s really important that this be reported in a scientifically accurate way, because we will all learn from this,” Lori J. West, MD, DPhil, said in an interview.

Little seems to be known for sure about the actual cause of death, “but the fact there was not hyperacute rejection is itself a big step forward. And we know, at least from the limited information we have, that it did not occur,” observed Dr. West, who directs the Alberta Transplant Institute, Edmonton, and the Canadian Donation and Transplantation Research Program. She is a professor of pediatrics with adjunct positions in the departments of surgery and microbiology/immunology.

Dr. West also sees Mr. Bennett’s struggle with infections and adjustments to his unique immunosuppressive regimen, at least as characterized by his care team, as in line with the experience of many heart transplant recipients facing the same threat.

“We already walk this tightrope with every transplant patient,” she said. Typically, they’re put on a somewhat standardized immunosuppressant regimen, “and then we modify it a bit, either increasing or decreasing it, depending on the posttransplant course.” The regimen can become especially intense in response to new signs of rejection, “and you know that that’s going to have an impact on susceptibility to all kinds of infections.”
 

Full circle

The porcine heart was protected along two fronts against assault from Mr. Bennett’s immune system and other inhospitable aspects of his physiology, either of which could also have been obstacles to success: Genetic modification (Revivicor) of the pig that provided the heart, and a singularly aggressive antirejection drug regimen for the patient.

The knockout of three genes targeting specific porcine cell-surface carbohydrates that provoke a strong human antibody response reportedly averted a hyperacute rejection response that would have caused the graft to fail almost immediately.

Other genetic manipulations, some using CRISPR technology, silenced genes encoded for porcine endogenous retroviruses. Others were aimed at controlling myocardial growth and stemming graft microangiopathy.  

Mr. Bennett himself was treated with powerful immunosuppressants, including an investigational anti-CD40 monoclonal antibody (KPL-404, Kiniksa Pharmaceuticals) that, according to UMSOM, inhibits a well-recognized pathway critical to B-cell proliferation, T-cell activation, and antibody production.

“I suspect the patient may not have had rejection, but unfortunately, that intense immunosuppression really set him up – even if he had been half that age – for a very difficult time,” David A. Baran, MD, a cardiologist from Sentara Advanced Heart Failure Center, Norfolk, Va., who studies transplant immunology, said in an interview.

“This is in some ways like the original heart transplant in 1967, when the ability to do the surgery evolved before understanding of the immunosuppression needed. Four or 5 years later, heart transplantation almost died out, before the development of better immunosuppressants like cyclosporine and later tacrolimus,” Dr. Baran said.

“The current age, when we use less immunosuppression than ever, is based on 30 years of progressive success,” he noted. This landmark xenotransplantation “basically turns back the clock to a time when the intensity of immunosuppression by definition had to be extremely high, because we really didn’t know what to expect.”
 

Emerging role of xeno-organs

Xenotransplantation has been touted as potential strategy for expanding the pool of organs available for transplantation. Mr. Bennett’s “breakthrough surgery” takes the world “one step closer to solving the organ shortage crisis,” his surgeon, Dr. Griffith, announced soon after the procedure. “There are simply not enough donor human hearts available to meet the long list of potential recipients.”

But it’s not the only proposed approach. Measures could be taken, for example, to make more efficient use of the human organs that become available, partly by opening the field to additional less-than-ideal hearts and loosening regulatory mandates for projected graft survival.

“Every year, more than two-thirds of donor organs in the United States are discarded. So it’s not actually that we don’t have enough organs, it’s that we don’t have enough organs that people are willing to take,” Dr. Baran said. Still, it’s important to pursue all promising avenues, and “the genetic manipulation pathway is remarkable.”

But “honestly, organs such as kidneys probably make the most sense” for early study of xenotransplantation from pigs, he said. “The waiting list for kidneys is also very long, but if the kidney graft were to fail, the patient wouldn’t die. It would allow us to work out the immunosuppression without putting patients’ lives at risk.”

Often overlooked in assessments of organ demand, Dr. West said, is that “a lot of patients who could benefit from a transplant will never even be listed for a transplant.” It’s not clear why; perhaps they have multiple comorbidities, live too far from a transplant center, “or they’re too big or too small. Even if there were unlimited organs, you could never meet the needs of people who could benefit from transplantation.”

So even if more available donor organs were used, she said, there would still be a gap that xenotransplantation could help fill. “I’m very much in favor of research that allows us to continue to try to find a pathway to xenotransplantation. I think it’s critically important.”

Unquestionably, “we now need to have a dialogue to entertain how a technology like this, using modern medicine with gene editing, is really going to be utilized,” Dr. Mehra said. The Bennett case “does open up the field, but it also raises caution.” There should be broad participation to move the field forward, “coordinated through either societies or nationally allocated advisory committees that oversee the movement of this technology, to the next step.”

Ideally, that next step “would be to do a safety clinical trial in the right patient,” he said. “And the right patient, by definition, would be one who does not have a life-prolonging option, either mechanical circulatory support or allograft transplantation. That would be the goal.”

Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board NuPulseCV, Leviticus, and FineHeart. Dr. Baran disclosed consulting for Getinge and LivaNova; speaking for Pfizer; and serving on trial steering committees for CareDx and Procyrion, all unrelated to xenotransplantation. Dr. West has declared no relevant conflicts.

A version of this article first appeared on Medscape.com.

The genetically altered pig’s heart “worked like a rock star, beautifully functioning,” the surgeon who performed the pioneering Jan. 7 xenotransplant procedure said in a press statement on the death of the patient, David Bennett Sr.

“He wasn’t able to overcome what turned out to be devastating – the debilitation from his previous period of heart failure, which was extreme,” said Bartley P. Griffith, MD, clinical director of the cardiac xenotransplantation program at the University of Maryland, Baltimore.

University of Maryland Medical Center

Representatives of the institution aren’t offering many details on the cause of Mr. Bennett’s death on March 8, 60 days after his operation, but said they will elaborate when their findings are formally published. But their comments seem to downplay the unique nature of the implanted heart itself as a culprit and instead implicate the patient’s diminished overall clinical condition and what grew into an ongoing battle with infections.

The 57-year-old Bennett, bedridden with end-stage heart failure, judged a poor candidate for a ventricular assist device, and on extracorporeal membrane oxygenation (ECMO), reportedly was offered the extraordinary surgery after being turned down for a conventional transplant at several major centers.

“Until day 45 or 50, he was doing very well,” Muhammad M. Mohiuddin, MD, the xenotransplantation program’s scientific director, observed in the statement. But infections soon took advantage of his hobbled immune system.

Given his “preexisting condition and how frail his body was,” Dr. Mohiuddin said, “we were having difficulty maintaining a balance between his immunosuppression and controlling his infection.” Mr. Bennett went into multiple organ failure and “I think that resulted in his passing away.”


 

Beyond wildest dreams

The surgeons confidently framed Mr. Bennett’s experience as a milestone for heart xenotransplantation. “The demonstration that it was possible, beyond the wildest dreams of most people in the field, even, at this point – that we were able to take a genetically engineered organ and watch it function flawlessly for 9 weeks – is pretty positive in terms of the potential of this therapy,” Dr. Griffith said.

But enough questions linger that others were more circumspect, even as they praised the accomplishment. “There’s no question that this is a historic event,” Mandeep R. Mehra, MD, of Harvard Medical School, and director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital, both in Boston, said in an interview.

Still, “I don’t think we should just conclude that it was the patient’s frailty or death from infection,” Dr. Mehra said. With so few details available, “I would be very careful in prematurely concluding that the problem did not reside with the heart but with the patient. We cannot be sure.”

For example, he noted, “6 to 8 weeks is right around the time when some cardiac complications, like accelerated forms of vasculopathy, could become evident.” Immune-mediated cardiac allograft vasculopathy is a common cause of heart transplant failure.

Or, “it could as easily have been the fact that immunosuppression was modified at 6 to 7 weeks in response to potential infection, which could have led to a cardiac compromise,” Dr. Mehra said. “We just don’t know.”

“It’s really important that this be reported in a scientifically accurate way, because we will all learn from this,” Lori J. West, MD, DPhil, said in an interview.

Little seems to be known for sure about the actual cause of death, “but the fact there was not hyperacute rejection is itself a big step forward. And we know, at least from the limited information we have, that it did not occur,” observed Dr. West, who directs the Alberta Transplant Institute, Edmonton, and the Canadian Donation and Transplantation Research Program. She is a professor of pediatrics with adjunct positions in the departments of surgery and microbiology/immunology.

Dr. West also sees Mr. Bennett’s struggle with infections and adjustments to his unique immunosuppressive regimen, at least as characterized by his care team, as in line with the experience of many heart transplant recipients facing the same threat.

“We already walk this tightrope with every transplant patient,” she said. Typically, they’re put on a somewhat standardized immunosuppressant regimen, “and then we modify it a bit, either increasing or decreasing it, depending on the posttransplant course.” The regimen can become especially intense in response to new signs of rejection, “and you know that that’s going to have an impact on susceptibility to all kinds of infections.”
 

Full circle

The porcine heart was protected along two fronts against assault from Mr. Bennett’s immune system and other inhospitable aspects of his physiology, either of which could also have been obstacles to success: Genetic modification (Revivicor) of the pig that provided the heart, and a singularly aggressive antirejection drug regimen for the patient.

The knockout of three genes targeting specific porcine cell-surface carbohydrates that provoke a strong human antibody response reportedly averted a hyperacute rejection response that would have caused the graft to fail almost immediately.

Other genetic manipulations, some using CRISPR technology, silenced genes encoded for porcine endogenous retroviruses. Others were aimed at controlling myocardial growth and stemming graft microangiopathy.  

Mr. Bennett himself was treated with powerful immunosuppressants, including an investigational anti-CD40 monoclonal antibody (KPL-404, Kiniksa Pharmaceuticals) that, according to UMSOM, inhibits a well-recognized pathway critical to B-cell proliferation, T-cell activation, and antibody production.

“I suspect the patient may not have had rejection, but unfortunately, that intense immunosuppression really set him up – even if he had been half that age – for a very difficult time,” David A. Baran, MD, a cardiologist from Sentara Advanced Heart Failure Center, Norfolk, Va., who studies transplant immunology, said in an interview.

“This is in some ways like the original heart transplant in 1967, when the ability to do the surgery evolved before understanding of the immunosuppression needed. Four or 5 years later, heart transplantation almost died out, before the development of better immunosuppressants like cyclosporine and later tacrolimus,” Dr. Baran said.

“The current age, when we use less immunosuppression than ever, is based on 30 years of progressive success,” he noted. This landmark xenotransplantation “basically turns back the clock to a time when the intensity of immunosuppression by definition had to be extremely high, because we really didn’t know what to expect.”
 

Emerging role of xeno-organs

Xenotransplantation has been touted as potential strategy for expanding the pool of organs available for transplantation. Mr. Bennett’s “breakthrough surgery” takes the world “one step closer to solving the organ shortage crisis,” his surgeon, Dr. Griffith, announced soon after the procedure. “There are simply not enough donor human hearts available to meet the long list of potential recipients.”

But it’s not the only proposed approach. Measures could be taken, for example, to make more efficient use of the human organs that become available, partly by opening the field to additional less-than-ideal hearts and loosening regulatory mandates for projected graft survival.

“Every year, more than two-thirds of donor organs in the United States are discarded. So it’s not actually that we don’t have enough organs, it’s that we don’t have enough organs that people are willing to take,” Dr. Baran said. Still, it’s important to pursue all promising avenues, and “the genetic manipulation pathway is remarkable.”

But “honestly, organs such as kidneys probably make the most sense” for early study of xenotransplantation from pigs, he said. “The waiting list for kidneys is also very long, but if the kidney graft were to fail, the patient wouldn’t die. It would allow us to work out the immunosuppression without putting patients’ lives at risk.”

Often overlooked in assessments of organ demand, Dr. West said, is that “a lot of patients who could benefit from a transplant will never even be listed for a transplant.” It’s not clear why; perhaps they have multiple comorbidities, live too far from a transplant center, “or they’re too big or too small. Even if there were unlimited organs, you could never meet the needs of people who could benefit from transplantation.”

So even if more available donor organs were used, she said, there would still be a gap that xenotransplantation could help fill. “I’m very much in favor of research that allows us to continue to try to find a pathway to xenotransplantation. I think it’s critically important.”

Unquestionably, “we now need to have a dialogue to entertain how a technology like this, using modern medicine with gene editing, is really going to be utilized,” Dr. Mehra said. The Bennett case “does open up the field, but it also raises caution.” There should be broad participation to move the field forward, “coordinated through either societies or nationally allocated advisory committees that oversee the movement of this technology, to the next step.”

Ideally, that next step “would be to do a safety clinical trial in the right patient,” he said. “And the right patient, by definition, would be one who does not have a life-prolonging option, either mechanical circulatory support or allograft transplantation. That would be the goal.”

Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board NuPulseCV, Leviticus, and FineHeart. Dr. Baran disclosed consulting for Getinge and LivaNova; speaking for Pfizer; and serving on trial steering committees for CareDx and Procyrion, all unrelated to xenotransplantation. Dr. West has declared no relevant conflicts.

A version of this article first appeared on Medscape.com.

The genetically altered pig’s heart “worked like a rock star, beautifully functioning,” the surgeon who performed the pioneering Jan. 7 xenotransplant procedure said in a press statement on the death of the patient, David Bennett Sr.

“He wasn’t able to overcome what turned out to be devastating – the debilitation from his previous period of heart failure, which was extreme,” said Bartley P. Griffith, MD, clinical director of the cardiac xenotransplantation program at the University of Maryland, Baltimore.

University of Maryland Medical Center

Representatives of the institution aren’t offering many details on the cause of Mr. Bennett’s death on March 8, 60 days after his operation, but said they will elaborate when their findings are formally published. But their comments seem to downplay the unique nature of the implanted heart itself as a culprit and instead implicate the patient’s diminished overall clinical condition and what grew into an ongoing battle with infections.

The 57-year-old Bennett, bedridden with end-stage heart failure, judged a poor candidate for a ventricular assist device, and on extracorporeal membrane oxygenation (ECMO), reportedly was offered the extraordinary surgery after being turned down for a conventional transplant at several major centers.

“Until day 45 or 50, he was doing very well,” Muhammad M. Mohiuddin, MD, the xenotransplantation program’s scientific director, observed in the statement. But infections soon took advantage of his hobbled immune system.

Given his “preexisting condition and how frail his body was,” Dr. Mohiuddin said, “we were having difficulty maintaining a balance between his immunosuppression and controlling his infection.” Mr. Bennett went into multiple organ failure and “I think that resulted in his passing away.”


 

Beyond wildest dreams

The surgeons confidently framed Mr. Bennett’s experience as a milestone for heart xenotransplantation. “The demonstration that it was possible, beyond the wildest dreams of most people in the field, even, at this point – that we were able to take a genetically engineered organ and watch it function flawlessly for 9 weeks – is pretty positive in terms of the potential of this therapy,” Dr. Griffith said.

But enough questions linger that others were more circumspect, even as they praised the accomplishment. “There’s no question that this is a historic event,” Mandeep R. Mehra, MD, of Harvard Medical School, and director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital, both in Boston, said in an interview.

Still, “I don’t think we should just conclude that it was the patient’s frailty or death from infection,” Dr. Mehra said. With so few details available, “I would be very careful in prematurely concluding that the problem did not reside with the heart but with the patient. We cannot be sure.”

For example, he noted, “6 to 8 weeks is right around the time when some cardiac complications, like accelerated forms of vasculopathy, could become evident.” Immune-mediated cardiac allograft vasculopathy is a common cause of heart transplant failure.

Or, “it could as easily have been the fact that immunosuppression was modified at 6 to 7 weeks in response to potential infection, which could have led to a cardiac compromise,” Dr. Mehra said. “We just don’t know.”

“It’s really important that this be reported in a scientifically accurate way, because we will all learn from this,” Lori J. West, MD, DPhil, said in an interview.

Little seems to be known for sure about the actual cause of death, “but the fact there was not hyperacute rejection is itself a big step forward. And we know, at least from the limited information we have, that it did not occur,” observed Dr. West, who directs the Alberta Transplant Institute, Edmonton, and the Canadian Donation and Transplantation Research Program. She is a professor of pediatrics with adjunct positions in the departments of surgery and microbiology/immunology.

Dr. West also sees Mr. Bennett’s struggle with infections and adjustments to his unique immunosuppressive regimen, at least as characterized by his care team, as in line with the experience of many heart transplant recipients facing the same threat.

“We already walk this tightrope with every transplant patient,” she said. Typically, they’re put on a somewhat standardized immunosuppressant regimen, “and then we modify it a bit, either increasing or decreasing it, depending on the posttransplant course.” The regimen can become especially intense in response to new signs of rejection, “and you know that that’s going to have an impact on susceptibility to all kinds of infections.”
 

Full circle

The porcine heart was protected along two fronts against assault from Mr. Bennett’s immune system and other inhospitable aspects of his physiology, either of which could also have been obstacles to success: Genetic modification (Revivicor) of the pig that provided the heart, and a singularly aggressive antirejection drug regimen for the patient.

The knockout of three genes targeting specific porcine cell-surface carbohydrates that provoke a strong human antibody response reportedly averted a hyperacute rejection response that would have caused the graft to fail almost immediately.

Other genetic manipulations, some using CRISPR technology, silenced genes encoded for porcine endogenous retroviruses. Others were aimed at controlling myocardial growth and stemming graft microangiopathy.  

Mr. Bennett himself was treated with powerful immunosuppressants, including an investigational anti-CD40 monoclonal antibody (KPL-404, Kiniksa Pharmaceuticals) that, according to UMSOM, inhibits a well-recognized pathway critical to B-cell proliferation, T-cell activation, and antibody production.

“I suspect the patient may not have had rejection, but unfortunately, that intense immunosuppression really set him up – even if he had been half that age – for a very difficult time,” David A. Baran, MD, a cardiologist from Sentara Advanced Heart Failure Center, Norfolk, Va., who studies transplant immunology, said in an interview.

“This is in some ways like the original heart transplant in 1967, when the ability to do the surgery evolved before understanding of the immunosuppression needed. Four or 5 years later, heart transplantation almost died out, before the development of better immunosuppressants like cyclosporine and later tacrolimus,” Dr. Baran said.

“The current age, when we use less immunosuppression than ever, is based on 30 years of progressive success,” he noted. This landmark xenotransplantation “basically turns back the clock to a time when the intensity of immunosuppression by definition had to be extremely high, because we really didn’t know what to expect.”
 

Emerging role of xeno-organs

Xenotransplantation has been touted as potential strategy for expanding the pool of organs available for transplantation. Mr. Bennett’s “breakthrough surgery” takes the world “one step closer to solving the organ shortage crisis,” his surgeon, Dr. Griffith, announced soon after the procedure. “There are simply not enough donor human hearts available to meet the long list of potential recipients.”

But it’s not the only proposed approach. Measures could be taken, for example, to make more efficient use of the human organs that become available, partly by opening the field to additional less-than-ideal hearts and loosening regulatory mandates for projected graft survival.

“Every year, more than two-thirds of donor organs in the United States are discarded. So it’s not actually that we don’t have enough organs, it’s that we don’t have enough organs that people are willing to take,” Dr. Baran said. Still, it’s important to pursue all promising avenues, and “the genetic manipulation pathway is remarkable.”

But “honestly, organs such as kidneys probably make the most sense” for early study of xenotransplantation from pigs, he said. “The waiting list for kidneys is also very long, but if the kidney graft were to fail, the patient wouldn’t die. It would allow us to work out the immunosuppression without putting patients’ lives at risk.”

Often overlooked in assessments of organ demand, Dr. West said, is that “a lot of patients who could benefit from a transplant will never even be listed for a transplant.” It’s not clear why; perhaps they have multiple comorbidities, live too far from a transplant center, “or they’re too big or too small. Even if there were unlimited organs, you could never meet the needs of people who could benefit from transplantation.”

So even if more available donor organs were used, she said, there would still be a gap that xenotransplantation could help fill. “I’m very much in favor of research that allows us to continue to try to find a pathway to xenotransplantation. I think it’s critically important.”

Unquestionably, “we now need to have a dialogue to entertain how a technology like this, using modern medicine with gene editing, is really going to be utilized,” Dr. Mehra said. The Bennett case “does open up the field, but it also raises caution.” There should be broad participation to move the field forward, “coordinated through either societies or nationally allocated advisory committees that oversee the movement of this technology, to the next step.”

Ideally, that next step “would be to do a safety clinical trial in the right patient,” he said. “And the right patient, by definition, would be one who does not have a life-prolonging option, either mechanical circulatory support or allograft transplantation. That would be the goal.”

Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board NuPulseCV, Leviticus, and FineHeart. Dr. Baran disclosed consulting for Getinge and LivaNova; speaking for Pfizer; and serving on trial steering committees for CareDx and Procyrion, all unrelated to xenotransplantation. Dr. West has declared no relevant conflicts.

A version of this article first appeared on Medscape.com.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

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The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.