Interventional Cardiology & Surgery

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

The proposal by the major cardiovascular societies in the US to form a new board of cardiovascular medicine to manage initial and ongoing certification of cardiologists represents something of a revolution in the field of continuing medical education and assessment of competency. 

Five US cardiovascular societies — the American College of Cardiology (ACC), the American Heart Association (AHA), the Heart Failure Society of America (HFSA), the Heart Rhythm Society (HRS), and the Society for Cardiovascular Angiography & Interventions (SCAI) — have now joined forces to propose a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM). 

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists as well as many other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.” 

The ABCVM is hoping to offer a more appropriate and supportive approach, according to Jeffrey Kuvin, MD, a trustee of the ACC, who has been heading up the working group to develop this plan. 

Dr. Kuvin, who is chair of the cardiology at Northwell Health, Manhasset, New York, a large academic healthcare system, explained that maintenance of certification has been a topic of discussion across the cardiovascular community for many years, and the ACC has a working group focused on the next steps for evaluation of competency, which he chairs.

“The topic of evaluation of competence has been on the mind of the ACC for many years and hence a work group was developed to focus on this,” Dr. Kuvin noted. “A lot of evolution of the concepts and next steps have been drawn out of this working group. And now other cardiovascular societies have joined to show unification across the house of cardiology and that this is indeed the way that the cardiovascular profession should move.” 
 

“Time to Separate from Internal Medicine”

The general concept behind the new cardiology board is to separate cardiology from the ABIM. 

“This is rooted from the concept that cardiology has evolved so much over the last few decades into such a large multidimensional specialty that it really does demarcate itself from internal medicine, and as such, it deserves a separate board governed by cardiologists with collaboration across the entirely of cardiology,” Dr. Kuvin said. 

Cardiology has had significant growth and expansion of technology, tools, medications, and the approach to patients in many specialities and subspecialties, he added. “We have defined training programs in many different areas within cardiology; we have our own guidelines, our own competency statements, and in many cases, cardiology exists as its own department outside of medicine in many institutions. It’s just time to separate cardiology from the umbrella of internal medicine.” 

The new cardiology board would be separate from, and not report to, the ABIM; rather, it would report directly to the American Board of Medical Specialties (ABMS), the only recognized medical certification body in the US. 
 

What Are the Proposed Changes

Under the present system, managed by the ABIM, clinicians must undergo two stages of certification to be a cardiologist. First, they have to pass the initial certification exam in general cardiology, and then exams in one of four subspecialties if they plan to enter one of these, including interventional cardiology, electrophysiology, advanced heart failure or adult congenital heart disease. 

Next, clinicians enter the maintenance of certification phase, which can take three different forms: 1) taking another recertification exam every 10 years; 2) the collaborative maintenance pathway — a collaboration between ACC and ABIM, which includes evaluation, learning and a certified exam each year; or 3) longitudinal knowledge and assessment — in which the program interacts with the clinician on an ongoing basis, sending secured questions regularly. 

All three of these pathways for maintenance of certification involve high stakes questions and a set bar for passing or failing. 

Under the proposed new cardiology board, an initial certification exam would still be required after fellowship training, but the maintenance of certification process would be completely restructured, with the new approach taking the form of continuous learning and assessment of competency. 

“This is an iterative process, but we envision with a new American Board of Cardiovascular Medicine, we will pick up where the ABIM left off,” Dr. Kuvin notes. “That includes an initial certifying examination for the five areas that already exist under the ABIM system but with the opportunities to expand that to further specialties as well.”

He points out that there are several areas in cardiology that are currently not represented by these five areas that warrant some discussion, including multimodality imaging, vascular heart disease, and cardio-oncology. 

“At present, everybody has to pass the general cardiology exam and then some may wish to further train and get certified in one of the other four other specific areas. But one topic that has been discussed over many years is how do we maintain competency in the areas in which clinicians practice over their lifetime as a cardiologist,” Dr. Kuvin commented. 

He said the proposed cardiology board would like to adhere to some basic principles that are fundamental to the practice of medicine. 

“We want to make sure that we are practicing medicine so that our patients derive the most benefit from seeing a cardiologist,” he said. “We also want to make sure, however, that this is a supportive process, supporting cardiologists to learn what they know and more importantly what they don’t know; to identify knowledge gaps in specific area; to help the cardiologist fill those knowledge gaps; to acknowledge those gaps have been filled; and then move on to another area of interest. This will be the focus of this new and improved model of continuous competency.”

The proposed new board also says it wants to make sure this is appropriate to the area in which the clinician is practicing.

“To take a closed book certified exam every 10 years on the world of cardiology as happens at the current time – or the assessments conducted in the other two pathways – is often meaningless to the cardiologist,” Dr. Kuvin says. “All three current pathways involve high stakes questions that are often irrelevant to one’s clinical practice.” 
 

Lifelong Learning

“The crux of the changes we are proposing will be away from the focus of passing a test towards a model of helping the individual with their competency, with continuous learning and evaluation of competency to help the clinician fill in their knowledge gaps,” he explains.

He described the new approach as “lifelong learning,” adding that, instead of it being “a punitive pass/fail environment with no feedback, which causes a lot of discontent among clinicians,” it will be a supportive process, where a clinician will be helped in filling their knowledge gaps. 

“I think this would be a welcome change not just for cardiology but across medical specialties,” Dr. Kuvin said. 

He also pointed out the ABMS itself is considering a continuous competency approach, and the proposed new cardiology board aims to work with the ABMS to make sure that their goals of continuous competency assessment are matched. 

“The world has changed. The ability to access information has changed. It is no longer imperative for a clinician to have every piece of knowledge in their brain, but rather to know how to get knowledge and to incorporate that knowledge into clinical practice,” Dr. Kuvin noted. “Competency should not involve knowledge alone as in a closed book exam. It is more about understanding the world that we live in, how to synthesize information, where we need to improve knowledge and how to do that.” 

Dr. Kuvin acknowledged that asking clinicians questions is a very helpful tool to identify their knowledge base and their knowledge gaps. “But we believe the clinician needs to be given resources — that could be a conference, an article, a simulation — to fill that knowledge gap. Then we could ask clinicians some different questions and if they get those right then we have provided a service.” 

Tactile skills for cardiologists needing to perform procedures – such as interventionalists or electrophysiologists may be incorporated by simulation in a technology-based scenario.

On how often these assessments would take place, Dr. Kuvin said that hadn’t been decided for sure. 

“We certainly do not think an assessment every 10 years is appropriate. We envision, instead of an episodic model, it will be rather a lifelong journey of education and competency. This will involve frequent contact and making sure knowledge gaps are being filled. There are criteria being set out by the ABMS that there should be a certain number of touch points with individuals on an annual as well as a 5-year basis to make sure cardiologists are staying within specific guardrails. The exact nature of these is yet to be determined,” he said. 

Dr. Kuvin added that it was not known yet what sort of hours would be required but added that “this will not be a significant time burden.”
 

What is the Timeframe?

The application to the ABMS for a separate cardiology board is still ongoing and has not yet received formal acceptance. Representatives from the five US cardiovascular societies are in the initial stages of formulating a transition board. 

“The submission to the ABMS will take time for them to review. This could take up to a year or so,” Dr. Kuvin estimates. 

This is the first time the ABMS has entertained the concept of a new board in many years, he noted. “It will be a paradigm shift for the whole country. I think that cardiology is really at the forefront and in a position where we can actually do this. If cardiovascular medicine is granted a new board, I think this will help change the approach of how physicians are assessed in terms of continuous competency not just in cardiology but across all specialties of medicine.”

He added: “We are confident that we can work within the construct of the ABMS guidelines that have been revised to be much more holistic in the approach of continuous competence across the board. This includes thinking beyond rote medical knowledge and thinking about the clinician as a whole and their abilities to communicate, act professionally, work within a complex medical system, utilize medical resources effectively. These all have to be part of continuous competence.”
 

How Much Will This Cost?

Noting that the ABIM has received criticism over the costs of the certification process, Dr. Kuvin said they intend to make this “as lean a machine as possible with the focus on reducing the financial [burden] as well as the time burden for cardiologists. It is very important that this is not cumbersome, that it is woven into clinical practice, and that it is not costly.” 

But he pointed out that building a new board will have significant costs. 

“We have to think about developing initial board certification examinations as well as changing the paradigm on continuous certification,” he said. “This will take some up-front costs, and our society partners have decided that they are willing to provide some start-up funds for this. We anticipate the initial certification will remain somewhat similar in price, but the cost of ongoing continuous competency assessment will be significantly reduced compared to today’s models.”

Dr. Kuvin said the collaboration of the five participating US cardiovascular societies was unprecedented. But he noted that while the transition board is beginning with representatives of these individual societies, it will ultimately be independent from these societies and have its own board of directors. 

He suggested that other societies representing other parts of cardiology are also interested. “Cardiology has recognized how important this is,” he said. “Everybody is excited about this.”

A version of this article appeared on Medscape.com.

The proposal by the major cardiovascular societies in the US to form a new board of cardiovascular medicine to manage initial and ongoing certification of cardiologists represents something of a revolution in the field of continuing medical education and assessment of competency. 

Five US cardiovascular societies — the American College of Cardiology (ACC), the American Heart Association (AHA), the Heart Failure Society of America (HFSA), the Heart Rhythm Society (HRS), and the Society for Cardiovascular Angiography & Interventions (SCAI) — have now joined forces to propose a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM). 

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists as well as many other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.” 

The ABCVM is hoping to offer a more appropriate and supportive approach, according to Jeffrey Kuvin, MD, a trustee of the ACC, who has been heading up the working group to develop this plan. 

Dr. Kuvin, who is chair of the cardiology at Northwell Health, Manhasset, New York, a large academic healthcare system, explained that maintenance of certification has been a topic of discussion across the cardiovascular community for many years, and the ACC has a working group focused on the next steps for evaluation of competency, which he chairs.

“The topic of evaluation of competence has been on the mind of the ACC for many years and hence a work group was developed to focus on this,” Dr. Kuvin noted. “A lot of evolution of the concepts and next steps have been drawn out of this working group. And now other cardiovascular societies have joined to show unification across the house of cardiology and that this is indeed the way that the cardiovascular profession should move.” 
 

“Time to Separate from Internal Medicine”

The general concept behind the new cardiology board is to separate cardiology from the ABIM. 

“This is rooted from the concept that cardiology has evolved so much over the last few decades into such a large multidimensional specialty that it really does demarcate itself from internal medicine, and as such, it deserves a separate board governed by cardiologists with collaboration across the entirely of cardiology,” Dr. Kuvin said. 

Cardiology has had significant growth and expansion of technology, tools, medications, and the approach to patients in many specialities and subspecialties, he added. “We have defined training programs in many different areas within cardiology; we have our own guidelines, our own competency statements, and in many cases, cardiology exists as its own department outside of medicine in many institutions. It’s just time to separate cardiology from the umbrella of internal medicine.” 

The new cardiology board would be separate from, and not report to, the ABIM; rather, it would report directly to the American Board of Medical Specialties (ABMS), the only recognized medical certification body in the US. 
 

What Are the Proposed Changes

Under the present system, managed by the ABIM, clinicians must undergo two stages of certification to be a cardiologist. First, they have to pass the initial certification exam in general cardiology, and then exams in one of four subspecialties if they plan to enter one of these, including interventional cardiology, electrophysiology, advanced heart failure or adult congenital heart disease. 

Next, clinicians enter the maintenance of certification phase, which can take three different forms: 1) taking another recertification exam every 10 years; 2) the collaborative maintenance pathway — a collaboration between ACC and ABIM, which includes evaluation, learning and a certified exam each year; or 3) longitudinal knowledge and assessment — in which the program interacts with the clinician on an ongoing basis, sending secured questions regularly. 

All three of these pathways for maintenance of certification involve high stakes questions and a set bar for passing or failing. 

Under the proposed new cardiology board, an initial certification exam would still be required after fellowship training, but the maintenance of certification process would be completely restructured, with the new approach taking the form of continuous learning and assessment of competency. 

“This is an iterative process, but we envision with a new American Board of Cardiovascular Medicine, we will pick up where the ABIM left off,” Dr. Kuvin notes. “That includes an initial certifying examination for the five areas that already exist under the ABIM system but with the opportunities to expand that to further specialties as well.”

He points out that there are several areas in cardiology that are currently not represented by these five areas that warrant some discussion, including multimodality imaging, vascular heart disease, and cardio-oncology. 

“At present, everybody has to pass the general cardiology exam and then some may wish to further train and get certified in one of the other four other specific areas. But one topic that has been discussed over many years is how do we maintain competency in the areas in which clinicians practice over their lifetime as a cardiologist,” Dr. Kuvin commented. 

He said the proposed cardiology board would like to adhere to some basic principles that are fundamental to the practice of medicine. 

“We want to make sure that we are practicing medicine so that our patients derive the most benefit from seeing a cardiologist,” he said. “We also want to make sure, however, that this is a supportive process, supporting cardiologists to learn what they know and more importantly what they don’t know; to identify knowledge gaps in specific area; to help the cardiologist fill those knowledge gaps; to acknowledge those gaps have been filled; and then move on to another area of interest. This will be the focus of this new and improved model of continuous competency.”

The proposed new board also says it wants to make sure this is appropriate to the area in which the clinician is practicing.

“To take a closed book certified exam every 10 years on the world of cardiology as happens at the current time – or the assessments conducted in the other two pathways – is often meaningless to the cardiologist,” Dr. Kuvin says. “All three current pathways involve high stakes questions that are often irrelevant to one’s clinical practice.” 
 

Lifelong Learning

“The crux of the changes we are proposing will be away from the focus of passing a test towards a model of helping the individual with their competency, with continuous learning and evaluation of competency to help the clinician fill in their knowledge gaps,” he explains.

He described the new approach as “lifelong learning,” adding that, instead of it being “a punitive pass/fail environment with no feedback, which causes a lot of discontent among clinicians,” it will be a supportive process, where a clinician will be helped in filling their knowledge gaps. 

“I think this would be a welcome change not just for cardiology but across medical specialties,” Dr. Kuvin said. 

He also pointed out the ABMS itself is considering a continuous competency approach, and the proposed new cardiology board aims to work with the ABMS to make sure that their goals of continuous competency assessment are matched. 

“The world has changed. The ability to access information has changed. It is no longer imperative for a clinician to have every piece of knowledge in their brain, but rather to know how to get knowledge and to incorporate that knowledge into clinical practice,” Dr. Kuvin noted. “Competency should not involve knowledge alone as in a closed book exam. It is more about understanding the world that we live in, how to synthesize information, where we need to improve knowledge and how to do that.” 

Dr. Kuvin acknowledged that asking clinicians questions is a very helpful tool to identify their knowledge base and their knowledge gaps. “But we believe the clinician needs to be given resources — that could be a conference, an article, a simulation — to fill that knowledge gap. Then we could ask clinicians some different questions and if they get those right then we have provided a service.” 

Tactile skills for cardiologists needing to perform procedures – such as interventionalists or electrophysiologists may be incorporated by simulation in a technology-based scenario.

On how often these assessments would take place, Dr. Kuvin said that hadn’t been decided for sure. 

“We certainly do not think an assessment every 10 years is appropriate. We envision, instead of an episodic model, it will be rather a lifelong journey of education and competency. This will involve frequent contact and making sure knowledge gaps are being filled. There are criteria being set out by the ABMS that there should be a certain number of touch points with individuals on an annual as well as a 5-year basis to make sure cardiologists are staying within specific guardrails. The exact nature of these is yet to be determined,” he said. 

Dr. Kuvin added that it was not known yet what sort of hours would be required but added that “this will not be a significant time burden.”
 

What is the Timeframe?

The application to the ABMS for a separate cardiology board is still ongoing and has not yet received formal acceptance. Representatives from the five US cardiovascular societies are in the initial stages of formulating a transition board. 

“The submission to the ABMS will take time for them to review. This could take up to a year or so,” Dr. Kuvin estimates. 

This is the first time the ABMS has entertained the concept of a new board in many years, he noted. “It will be a paradigm shift for the whole country. I think that cardiology is really at the forefront and in a position where we can actually do this. If cardiovascular medicine is granted a new board, I think this will help change the approach of how physicians are assessed in terms of continuous competency not just in cardiology but across all specialties of medicine.”

He added: “We are confident that we can work within the construct of the ABMS guidelines that have been revised to be much more holistic in the approach of continuous competence across the board. This includes thinking beyond rote medical knowledge and thinking about the clinician as a whole and their abilities to communicate, act professionally, work within a complex medical system, utilize medical resources effectively. These all have to be part of continuous competence.”
 

How Much Will This Cost?

Noting that the ABIM has received criticism over the costs of the certification process, Dr. Kuvin said they intend to make this “as lean a machine as possible with the focus on reducing the financial [burden] as well as the time burden for cardiologists. It is very important that this is not cumbersome, that it is woven into clinical practice, and that it is not costly.” 

But he pointed out that building a new board will have significant costs. 

“We have to think about developing initial board certification examinations as well as changing the paradigm on continuous certification,” he said. “This will take some up-front costs, and our society partners have decided that they are willing to provide some start-up funds for this. We anticipate the initial certification will remain somewhat similar in price, but the cost of ongoing continuous competency assessment will be significantly reduced compared to today’s models.”

Dr. Kuvin said the collaboration of the five participating US cardiovascular societies was unprecedented. But he noted that while the transition board is beginning with representatives of these individual societies, it will ultimately be independent from these societies and have its own board of directors. 

He suggested that other societies representing other parts of cardiology are also interested. “Cardiology has recognized how important this is,” he said. “Everybody is excited about this.”

A version of this article appeared on Medscape.com.

The proposal by the major cardiovascular societies in the US to form a new board of cardiovascular medicine to manage initial and ongoing certification of cardiologists represents something of a revolution in the field of continuing medical education and assessment of competency. 

Five US cardiovascular societies — the American College of Cardiology (ACC), the American Heart Association (AHA), the Heart Failure Society of America (HFSA), the Heart Rhythm Society (HRS), and the Society for Cardiovascular Angiography & Interventions (SCAI) — have now joined forces to propose a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM). 

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists as well as many other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.” 

The ABCVM is hoping to offer a more appropriate and supportive approach, according to Jeffrey Kuvin, MD, a trustee of the ACC, who has been heading up the working group to develop this plan. 

Dr. Kuvin, who is chair of the cardiology at Northwell Health, Manhasset, New York, a large academic healthcare system, explained that maintenance of certification has been a topic of discussion across the cardiovascular community for many years, and the ACC has a working group focused on the next steps for evaluation of competency, which he chairs.

“The topic of evaluation of competence has been on the mind of the ACC for many years and hence a work group was developed to focus on this,” Dr. Kuvin noted. “A lot of evolution of the concepts and next steps have been drawn out of this working group. And now other cardiovascular societies have joined to show unification across the house of cardiology and that this is indeed the way that the cardiovascular profession should move.” 
 

“Time to Separate from Internal Medicine”

The general concept behind the new cardiology board is to separate cardiology from the ABIM. 

“This is rooted from the concept that cardiology has evolved so much over the last few decades into such a large multidimensional specialty that it really does demarcate itself from internal medicine, and as such, it deserves a separate board governed by cardiologists with collaboration across the entirely of cardiology,” Dr. Kuvin said. 

Cardiology has had significant growth and expansion of technology, tools, medications, and the approach to patients in many specialities and subspecialties, he added. “We have defined training programs in many different areas within cardiology; we have our own guidelines, our own competency statements, and in many cases, cardiology exists as its own department outside of medicine in many institutions. It’s just time to separate cardiology from the umbrella of internal medicine.” 

The new cardiology board would be separate from, and not report to, the ABIM; rather, it would report directly to the American Board of Medical Specialties (ABMS), the only recognized medical certification body in the US. 
 

What Are the Proposed Changes

Under the present system, managed by the ABIM, clinicians must undergo two stages of certification to be a cardiologist. First, they have to pass the initial certification exam in general cardiology, and then exams in one of four subspecialties if they plan to enter one of these, including interventional cardiology, electrophysiology, advanced heart failure or adult congenital heart disease. 

Next, clinicians enter the maintenance of certification phase, which can take three different forms: 1) taking another recertification exam every 10 years; 2) the collaborative maintenance pathway — a collaboration between ACC and ABIM, which includes evaluation, learning and a certified exam each year; or 3) longitudinal knowledge and assessment — in which the program interacts with the clinician on an ongoing basis, sending secured questions regularly. 

All three of these pathways for maintenance of certification involve high stakes questions and a set bar for passing or failing. 

Under the proposed new cardiology board, an initial certification exam would still be required after fellowship training, but the maintenance of certification process would be completely restructured, with the new approach taking the form of continuous learning and assessment of competency. 

“This is an iterative process, but we envision with a new American Board of Cardiovascular Medicine, we will pick up where the ABIM left off,” Dr. Kuvin notes. “That includes an initial certifying examination for the five areas that already exist under the ABIM system but with the opportunities to expand that to further specialties as well.”

He points out that there are several areas in cardiology that are currently not represented by these five areas that warrant some discussion, including multimodality imaging, vascular heart disease, and cardio-oncology. 

“At present, everybody has to pass the general cardiology exam and then some may wish to further train and get certified in one of the other four other specific areas. But one topic that has been discussed over many years is how do we maintain competency in the areas in which clinicians practice over their lifetime as a cardiologist,” Dr. Kuvin commented. 

He said the proposed cardiology board would like to adhere to some basic principles that are fundamental to the practice of medicine. 

“We want to make sure that we are practicing medicine so that our patients derive the most benefit from seeing a cardiologist,” he said. “We also want to make sure, however, that this is a supportive process, supporting cardiologists to learn what they know and more importantly what they don’t know; to identify knowledge gaps in specific area; to help the cardiologist fill those knowledge gaps; to acknowledge those gaps have been filled; and then move on to another area of interest. This will be the focus of this new and improved model of continuous competency.”

The proposed new board also says it wants to make sure this is appropriate to the area in which the clinician is practicing.

“To take a closed book certified exam every 10 years on the world of cardiology as happens at the current time – or the assessments conducted in the other two pathways – is often meaningless to the cardiologist,” Dr. Kuvin says. “All three current pathways involve high stakes questions that are often irrelevant to one’s clinical practice.” 
 

Lifelong Learning

“The crux of the changes we are proposing will be away from the focus of passing a test towards a model of helping the individual with their competency, with continuous learning and evaluation of competency to help the clinician fill in their knowledge gaps,” he explains.

He described the new approach as “lifelong learning,” adding that, instead of it being “a punitive pass/fail environment with no feedback, which causes a lot of discontent among clinicians,” it will be a supportive process, where a clinician will be helped in filling their knowledge gaps. 

“I think this would be a welcome change not just for cardiology but across medical specialties,” Dr. Kuvin said. 

He also pointed out the ABMS itself is considering a continuous competency approach, and the proposed new cardiology board aims to work with the ABMS to make sure that their goals of continuous competency assessment are matched. 

“The world has changed. The ability to access information has changed. It is no longer imperative for a clinician to have every piece of knowledge in their brain, but rather to know how to get knowledge and to incorporate that knowledge into clinical practice,” Dr. Kuvin noted. “Competency should not involve knowledge alone as in a closed book exam. It is more about understanding the world that we live in, how to synthesize information, where we need to improve knowledge and how to do that.” 

Dr. Kuvin acknowledged that asking clinicians questions is a very helpful tool to identify their knowledge base and their knowledge gaps. “But we believe the clinician needs to be given resources — that could be a conference, an article, a simulation — to fill that knowledge gap. Then we could ask clinicians some different questions and if they get those right then we have provided a service.” 

Tactile skills for cardiologists needing to perform procedures – such as interventionalists or electrophysiologists may be incorporated by simulation in a technology-based scenario.

On how often these assessments would take place, Dr. Kuvin said that hadn’t been decided for sure. 

“We certainly do not think an assessment every 10 years is appropriate. We envision, instead of an episodic model, it will be rather a lifelong journey of education and competency. This will involve frequent contact and making sure knowledge gaps are being filled. There are criteria being set out by the ABMS that there should be a certain number of touch points with individuals on an annual as well as a 5-year basis to make sure cardiologists are staying within specific guardrails. The exact nature of these is yet to be determined,” he said. 

Dr. Kuvin added that it was not known yet what sort of hours would be required but added that “this will not be a significant time burden.”
 

What is the Timeframe?

The application to the ABMS for a separate cardiology board is still ongoing and has not yet received formal acceptance. Representatives from the five US cardiovascular societies are in the initial stages of formulating a transition board. 

“The submission to the ABMS will take time for them to review. This could take up to a year or so,” Dr. Kuvin estimates. 

This is the first time the ABMS has entertained the concept of a new board in many years, he noted. “It will be a paradigm shift for the whole country. I think that cardiology is really at the forefront and in a position where we can actually do this. If cardiovascular medicine is granted a new board, I think this will help change the approach of how physicians are assessed in terms of continuous competency not just in cardiology but across all specialties of medicine.”

He added: “We are confident that we can work within the construct of the ABMS guidelines that have been revised to be much more holistic in the approach of continuous competence across the board. This includes thinking beyond rote medical knowledge and thinking about the clinician as a whole and their abilities to communicate, act professionally, work within a complex medical system, utilize medical resources effectively. These all have to be part of continuous competence.”
 

How Much Will This Cost?

Noting that the ABIM has received criticism over the costs of the certification process, Dr. Kuvin said they intend to make this “as lean a machine as possible with the focus on reducing the financial [burden] as well as the time burden for cardiologists. It is very important that this is not cumbersome, that it is woven into clinical practice, and that it is not costly.” 

But he pointed out that building a new board will have significant costs. 

“We have to think about developing initial board certification examinations as well as changing the paradigm on continuous certification,” he said. “This will take some up-front costs, and our society partners have decided that they are willing to provide some start-up funds for this. We anticipate the initial certification will remain somewhat similar in price, but the cost of ongoing continuous competency assessment will be significantly reduced compared to today’s models.”

Dr. Kuvin said the collaboration of the five participating US cardiovascular societies was unprecedented. But he noted that while the transition board is beginning with representatives of these individual societies, it will ultimately be independent from these societies and have its own board of directors. 

He suggested that other societies representing other parts of cardiology are also interested. “Cardiology has recognized how important this is,” he said. “Everybody is excited about this.”

A version of this article appeared on Medscape.com.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

For high-risk surgical patients with severe symptomatic mitral regurgitation (MR), insertion of the Tendyne transcatheter mitral valve replacement (TMVR; Abbott) using a cardiac transapical approach resulted in excellent procedural success, relief of mitral regurgitation, and increases in cardiac hemodynamics and quality of life sustained at 1 year.

Further, patients with severe mitral annular calcification (MAC) showed improvements in hemodynamics, functional status, and quality of life after the procedure.

With 70 centers participating in the Tendyne SUMMIT trial, the first 100 trial roll-in patients accrued from the first one or two patients from each site without previous Tendyne TMVR experience.

“For this new procedure, with new operators, there was no intraprocedural mortality, and procedural survival was 100%,” co-primary investigator Jason Rogers, MD, of the University of California Davis Medical Center, Sacramento, told attendees at a Late-Breaking Clinical Science session at the Transcatheter Cardiovascular Therapeutics annual meeting.

“The survival was 74% at 12 months. The valve was very effective at eliminating much regurgitation, and 96.5% of patients had either zero or 1+ at a year, and 97% at 30 days had no mitral regurgitation,” he reported. As follow-up was during the COVID-19 pandemic, several of the deaths were attributed to COVID.
 

Device and trial designs

The Tendyne TMVR is placed through the cardiac apex. It has an outer frame contoured to comport with the shape of the native mitral valve. Inside is a circular, self-expanding, tri-leaflet bioprosthetic valve.

A unique aspect of the design is a tether attached to the outflow side of the valve to allow positioning and control of the valve. At the end of the tether is an apical pad that is placed over the apical access site to control bleeding. The device is currently limited to investigational use in the United States.

The trial enrolled patients with grade III/IV MR or severe MAC if valve anatomy was deemed amenable to transcatheter repair or met MitraClip indications and if these treatments were considered more appropriate than surgery.

Dr. Rogers reported on the first 100 roll-in (early experimental) patients who received Tendyne TMVR. There was a separate severe MAC cohort receiving Tendyne implantation (N = 103). A further 1:1 randomized study of 382 patients compared Tendyne investigational treatment with a MitraClip control group.

At baseline, the 100 roll-in patients had an average age of 75 years, 54% were men, 46% had a frailty score of 2 or greater, and 41% had been hospitalized in the prior 12 months for heart failure. Left ventricular ejection fraction (LVEF) was 48.6% ± 10.3%.
 

Improved cardiac function

Procedural survival was 100%, technical success 94%, and valve implantation occurred in 97%. Of the first 100 patients, 26 had died by 1 year, and two withdrew consent, leaving 72 for evaluation.

Immediate post-procedure survival was 98%, 87.9% at 3 months, 83.7% at 6 months, and 74.3% at 1 year. MR severity decreased from 29% 3+ and 69% 4+ at baseline to 96.5% 0/1+ and 3.5% 2+ at 1 year.

Cumulative adverse outcomes at 1 year were 27% all-cause mortality, 21.6% cardiovascular mortality, 5.4% all-cause stroke, 2.3% myocardial infarction (MI), 2.2% post-operative mitral reintervention, no major but 2.3% minor device thrombosis, and 32.4% major bleeding.

Most adverse events occurred peri-procedurally or within the first month, representing, “I think, a new procedure with new operators and a high real risk population,” Dr. Rogers said.

Echocardiography at 1 year compared with baseline showed significant changes with decreases in left ventricular end diastolic volume (LVEDV), increases in cardiac output (CO) and forward stroke volume, and no change in mitral valve gradient or left ventricular outflow tract (LVOT) gradient. New York Heart Association (NYHA) classification decreased from 69% class III/IV at baseline to 20% at 1 year, at which point 80% of patients were in class I/II.

“There was a consistent and steady improvement in KCCQ [Kansas City Cardiomyopathy Questionnaire] score, as expected, as patients recovered from this invasive procedure,” Dr. Rogers said. The 1-year score was 68.7, representing fair to good quality of life.
 

Outcomes with severe MAC

After screening for MR 3+ or greater, severe mitral stenosis, or moderate MR plus mitral stenosis, 103 eligible patients were treated with the Tendyne device. The median MAC volume of the cohort was 4000 mm3, with a maximum of 38,000 mm3.

Patients averaged 78 years old, 44.7% male, 55.3% had a frailty score of 2 or greater, 73.8% were in NYHA class III or greater, and 29.1% had been hospitalized within the prior 12 months for heart failure. Grade III or IV MR severity was present in 89%, with MR being primary in 90.3% of patients, and 10.7% had severe mitral stenosis.

Tendyne procedure survival was 98.1%, technical success was 94.2%, and valves were implanted in all patients. Emergency surgery or other intervention was required in 5.8%.

As co-presenter of the SUMMIT results, Vinod Thourani, MD, of the Piedmont Heart Institute in Atlanta, said at 30 days there was 6.8% all-cause mortality, all of it cardiovascular. There was one disabling stroke, one MI, no device thrombosis, and 21.4% major bleeding.

“At 1 month, there was less than grade 1 mitral regurgitation in all patients,” he reported, vs. 89% grade 3+/4+ at baseline. “At 1 month, it was an improvement in the NYHA classification to almost 70% in class I or II, which was improved from baseline of 26% in NYHA class I or II.”

Hemodynamic parameters all showed improvement, with a reduction in LVEF, LVEDV, and mitral valve gradient and increases in CO and forward stroke volume. There was no significant increase in LVOT gradient.

There was a small improvement in the KCCQ quality of life score from a baseline score of 49.2 to 52.3 at 30 days. “We’re expecting the KCCQ overall score to improve on 1 year follow up since the patients [are] still recovering from their thoracotomy incision,” Dr. Thourani predicted.

The primary endpoint will be evaluated at 1 year post procedure, he said at the meeting, sponsored by the Cardiovascular Research Foundation.
 

No good option

Designated discussant Joanna Chikwe, MD, chair of cardiac surgery at Cedars-Sinai Medical Center in Los Angeles, first thanked the presenters for their trial, saying, “What an absolute pleasure to be a mitral surgeon at a meeting where you’re presenting a solution for something that we find incredibly challenging. There’s no good transcatheter option for MAC. There’s no great surgical option for MAC.”

She noted the small size of the MAC cohort and asked what drove failure in patient screening, starting with 474 patients, identifying 120 who would be eligible, and enrolling 103 in the MAC cohort. The presenters identified neo-LVOT, the residual LVOT created after implanting the mitral valve prosthesis. Screening also eliminated patients with a too large or too small annulus.

Dr. Thourani said in Europe, surgeons have used anterior leaflet splitting before Tendyne, which may help to expand the population of eligible patients, but no leaflet modification was allowed in the SUMMIT trial.

Dr. Chikwe then pointed to the six deaths in the MAC arm and 11 deaths in the roll-in arm and asked about the mechanism of these deaths. “Was it [that] the 22% major bleeding is transapical? Really the Achilles heel of this procedure? Is this something that could become a transcatheter device?”

“We call it a transcatheter procedure, but it’s very much a surgical procedure,” Dr. Rogers answered. “And, you know, despite having great experienced sites...many surgeons don’t deal with the apex very much.” Furthermore, catheter insertion can lead to bleeding complications.

He noted that the roll-in patients were the first one or two cases at each site, and there have been improvements with site experience. The apical pads assist in hemostasis. He said the current design of the Tendyne catheter-delivered valve does not allow it to be adapted to a transfemoral transseptal approach.

Dr. Rogers is a consultant to and co-national principal investigator of the SUMMIT Pivotal Trial for Abbott. He is a consultant to Boston Scientific and a consultant/equity holder in Laminar. Dr. Thourani has received grant/research support from Abbott Vascular, Artivion, AtriCure, Boston Scientific, Croivalve, Edwards Lifesciences, JenaValve, Medtronic, and Trisol; consultant fees/honoraria from Abbott Vascular, Artivion, AtriCure, Boston Scientific, Croivalve, and Edwards Lifesciences; and has an executive role/ownership interest in DASI Simulations. Dr. Chikwe reports no relevant financial relationships. The SUMMIT trial was sponsored by Abbott.

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

For high-risk surgical patients with severe symptomatic mitral regurgitation (MR), insertion of the Tendyne transcatheter mitral valve replacement (TMVR; Abbott) using a cardiac transapical approach resulted in excellent procedural success, relief of mitral regurgitation, and increases in cardiac hemodynamics and quality of life sustained at 1 year.

Further, patients with severe mitral annular calcification (MAC) showed improvements in hemodynamics, functional status, and quality of life after the procedure.

With 70 centers participating in the Tendyne SUMMIT trial, the first 100 trial roll-in patients accrued from the first one or two patients from each site without previous Tendyne TMVR experience.

“For this new procedure, with new operators, there was no intraprocedural mortality, and procedural survival was 100%,” co-primary investigator Jason Rogers, MD, of the University of California Davis Medical Center, Sacramento, told attendees at a Late-Breaking Clinical Science session at the Transcatheter Cardiovascular Therapeutics annual meeting.

“The survival was 74% at 12 months. The valve was very effective at eliminating much regurgitation, and 96.5% of patients had either zero or 1+ at a year, and 97% at 30 days had no mitral regurgitation,” he reported. As follow-up was during the COVID-19 pandemic, several of the deaths were attributed to COVID.
 

Device and trial designs

The Tendyne TMVR is placed through the cardiac apex. It has an outer frame contoured to comport with the shape of the native mitral valve. Inside is a circular, self-expanding, tri-leaflet bioprosthetic valve.

A unique aspect of the design is a tether attached to the outflow side of the valve to allow positioning and control of the valve. At the end of the tether is an apical pad that is placed over the apical access site to control bleeding. The device is currently limited to investigational use in the United States.

The trial enrolled patients with grade III/IV MR or severe MAC if valve anatomy was deemed amenable to transcatheter repair or met MitraClip indications and if these treatments were considered more appropriate than surgery.

Dr. Rogers reported on the first 100 roll-in (early experimental) patients who received Tendyne TMVR. There was a separate severe MAC cohort receiving Tendyne implantation (N = 103). A further 1:1 randomized study of 382 patients compared Tendyne investigational treatment with a MitraClip control group.

At baseline, the 100 roll-in patients had an average age of 75 years, 54% were men, 46% had a frailty score of 2 or greater, and 41% had been hospitalized in the prior 12 months for heart failure. Left ventricular ejection fraction (LVEF) was 48.6% ± 10.3%.
 

Improved cardiac function

Procedural survival was 100%, technical success 94%, and valve implantation occurred in 97%. Of the first 100 patients, 26 had died by 1 year, and two withdrew consent, leaving 72 for evaluation.

Immediate post-procedure survival was 98%, 87.9% at 3 months, 83.7% at 6 months, and 74.3% at 1 year. MR severity decreased from 29% 3+ and 69% 4+ at baseline to 96.5% 0/1+ and 3.5% 2+ at 1 year.

Cumulative adverse outcomes at 1 year were 27% all-cause mortality, 21.6% cardiovascular mortality, 5.4% all-cause stroke, 2.3% myocardial infarction (MI), 2.2% post-operative mitral reintervention, no major but 2.3% minor device thrombosis, and 32.4% major bleeding.

Most adverse events occurred peri-procedurally or within the first month, representing, “I think, a new procedure with new operators and a high real risk population,” Dr. Rogers said.

Echocardiography at 1 year compared with baseline showed significant changes with decreases in left ventricular end diastolic volume (LVEDV), increases in cardiac output (CO) and forward stroke volume, and no change in mitral valve gradient or left ventricular outflow tract (LVOT) gradient. New York Heart Association (NYHA) classification decreased from 69% class III/IV at baseline to 20% at 1 year, at which point 80% of patients were in class I/II.

“There was a consistent and steady improvement in KCCQ [Kansas City Cardiomyopathy Questionnaire] score, as expected, as patients recovered from this invasive procedure,” Dr. Rogers said. The 1-year score was 68.7, representing fair to good quality of life.
 

Outcomes with severe MAC

After screening for MR 3+ or greater, severe mitral stenosis, or moderate MR plus mitral stenosis, 103 eligible patients were treated with the Tendyne device. The median MAC volume of the cohort was 4000 mm3, with a maximum of 38,000 mm3.

Patients averaged 78 years old, 44.7% male, 55.3% had a frailty score of 2 or greater, 73.8% were in NYHA class III or greater, and 29.1% had been hospitalized within the prior 12 months for heart failure. Grade III or IV MR severity was present in 89%, with MR being primary in 90.3% of patients, and 10.7% had severe mitral stenosis.

Tendyne procedure survival was 98.1%, technical success was 94.2%, and valves were implanted in all patients. Emergency surgery or other intervention was required in 5.8%.

As co-presenter of the SUMMIT results, Vinod Thourani, MD, of the Piedmont Heart Institute in Atlanta, said at 30 days there was 6.8% all-cause mortality, all of it cardiovascular. There was one disabling stroke, one MI, no device thrombosis, and 21.4% major bleeding.

“At 1 month, there was less than grade 1 mitral regurgitation in all patients,” he reported, vs. 89% grade 3+/4+ at baseline. “At 1 month, it was an improvement in the NYHA classification to almost 70% in class I or II, which was improved from baseline of 26% in NYHA class I or II.”

Hemodynamic parameters all showed improvement, with a reduction in LVEF, LVEDV, and mitral valve gradient and increases in CO and forward stroke volume. There was no significant increase in LVOT gradient.

There was a small improvement in the KCCQ quality of life score from a baseline score of 49.2 to 52.3 at 30 days. “We’re expecting the KCCQ overall score to improve on 1 year follow up since the patients [are] still recovering from their thoracotomy incision,” Dr. Thourani predicted.

The primary endpoint will be evaluated at 1 year post procedure, he said at the meeting, sponsored by the Cardiovascular Research Foundation.
 

No good option

Designated discussant Joanna Chikwe, MD, chair of cardiac surgery at Cedars-Sinai Medical Center in Los Angeles, first thanked the presenters for their trial, saying, “What an absolute pleasure to be a mitral surgeon at a meeting where you’re presenting a solution for something that we find incredibly challenging. There’s no good transcatheter option for MAC. There’s no great surgical option for MAC.”

She noted the small size of the MAC cohort and asked what drove failure in patient screening, starting with 474 patients, identifying 120 who would be eligible, and enrolling 103 in the MAC cohort. The presenters identified neo-LVOT, the residual LVOT created after implanting the mitral valve prosthesis. Screening also eliminated patients with a too large or too small annulus.

Dr. Thourani said in Europe, surgeons have used anterior leaflet splitting before Tendyne, which may help to expand the population of eligible patients, but no leaflet modification was allowed in the SUMMIT trial.

Dr. Chikwe then pointed to the six deaths in the MAC arm and 11 deaths in the roll-in arm and asked about the mechanism of these deaths. “Was it [that] the 22% major bleeding is transapical? Really the Achilles heel of this procedure? Is this something that could become a transcatheter device?”

“We call it a transcatheter procedure, but it’s very much a surgical procedure,” Dr. Rogers answered. “And, you know, despite having great experienced sites...many surgeons don’t deal with the apex very much.” Furthermore, catheter insertion can lead to bleeding complications.

He noted that the roll-in patients were the first one or two cases at each site, and there have been improvements with site experience. The apical pads assist in hemostasis. He said the current design of the Tendyne catheter-delivered valve does not allow it to be adapted to a transfemoral transseptal approach.

Dr. Rogers is a consultant to and co-national principal investigator of the SUMMIT Pivotal Trial for Abbott. He is a consultant to Boston Scientific and a consultant/equity holder in Laminar. Dr. Thourani has received grant/research support from Abbott Vascular, Artivion, AtriCure, Boston Scientific, Croivalve, Edwards Lifesciences, JenaValve, Medtronic, and Trisol; consultant fees/honoraria from Abbott Vascular, Artivion, AtriCure, Boston Scientific, Croivalve, and Edwards Lifesciences; and has an executive role/ownership interest in DASI Simulations. Dr. Chikwe reports no relevant financial relationships. The SUMMIT trial was sponsored by Abbott.

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

For high-risk surgical patients with severe symptomatic mitral regurgitation (MR), insertion of the Tendyne transcatheter mitral valve replacement (TMVR; Abbott) using a cardiac transapical approach resulted in excellent procedural success, relief of mitral regurgitation, and increases in cardiac hemodynamics and quality of life sustained at 1 year.

Further, patients with severe mitral annular calcification (MAC) showed improvements in hemodynamics, functional status, and quality of life after the procedure.

With 70 centers participating in the Tendyne SUMMIT trial, the first 100 trial roll-in patients accrued from the first one or two patients from each site without previous Tendyne TMVR experience.

“For this new procedure, with new operators, there was no intraprocedural mortality, and procedural survival was 100%,” co-primary investigator Jason Rogers, MD, of the University of California Davis Medical Center, Sacramento, told attendees at a Late-Breaking Clinical Science session at the Transcatheter Cardiovascular Therapeutics annual meeting.

“The survival was 74% at 12 months. The valve was very effective at eliminating much regurgitation, and 96.5% of patients had either zero or 1+ at a year, and 97% at 30 days had no mitral regurgitation,” he reported. As follow-up was during the COVID-19 pandemic, several of the deaths were attributed to COVID.
 

Device and trial designs

The Tendyne TMVR is placed through the cardiac apex. It has an outer frame contoured to comport with the shape of the native mitral valve. Inside is a circular, self-expanding, tri-leaflet bioprosthetic valve.

A unique aspect of the design is a tether attached to the outflow side of the valve to allow positioning and control of the valve. At the end of the tether is an apical pad that is placed over the apical access site to control bleeding. The device is currently limited to investigational use in the United States.

The trial enrolled patients with grade III/IV MR or severe MAC if valve anatomy was deemed amenable to transcatheter repair or met MitraClip indications and if these treatments were considered more appropriate than surgery.

Dr. Rogers reported on the first 100 roll-in (early experimental) patients who received Tendyne TMVR. There was a separate severe MAC cohort receiving Tendyne implantation (N = 103). A further 1:1 randomized study of 382 patients compared Tendyne investigational treatment with a MitraClip control group.

At baseline, the 100 roll-in patients had an average age of 75 years, 54% were men, 46% had a frailty score of 2 or greater, and 41% had been hospitalized in the prior 12 months for heart failure. Left ventricular ejection fraction (LVEF) was 48.6% ± 10.3%.
 

Improved cardiac function

Procedural survival was 100%, technical success 94%, and valve implantation occurred in 97%. Of the first 100 patients, 26 had died by 1 year, and two withdrew consent, leaving 72 for evaluation.

Immediate post-procedure survival was 98%, 87.9% at 3 months, 83.7% at 6 months, and 74.3% at 1 year. MR severity decreased from 29% 3+ and 69% 4+ at baseline to 96.5% 0/1+ and 3.5% 2+ at 1 year.

Cumulative adverse outcomes at 1 year were 27% all-cause mortality, 21.6% cardiovascular mortality, 5.4% all-cause stroke, 2.3% myocardial infarction (MI), 2.2% post-operative mitral reintervention, no major but 2.3% minor device thrombosis, and 32.4% major bleeding.

Most adverse events occurred peri-procedurally or within the first month, representing, “I think, a new procedure with new operators and a high real risk population,” Dr. Rogers said.

Echocardiography at 1 year compared with baseline showed significant changes with decreases in left ventricular end diastolic volume (LVEDV), increases in cardiac output (CO) and forward stroke volume, and no change in mitral valve gradient or left ventricular outflow tract (LVOT) gradient. New York Heart Association (NYHA) classification decreased from 69% class III/IV at baseline to 20% at 1 year, at which point 80% of patients were in class I/II.

“There was a consistent and steady improvement in KCCQ [Kansas City Cardiomyopathy Questionnaire] score, as expected, as patients recovered from this invasive procedure,” Dr. Rogers said. The 1-year score was 68.7, representing fair to good quality of life.
 

Outcomes with severe MAC

After screening for MR 3+ or greater, severe mitral stenosis, or moderate MR plus mitral stenosis, 103 eligible patients were treated with the Tendyne device. The median MAC volume of the cohort was 4000 mm3, with a maximum of 38,000 mm3.

Patients averaged 78 years old, 44.7% male, 55.3% had a frailty score of 2 or greater, 73.8% were in NYHA class III or greater, and 29.1% had been hospitalized within the prior 12 months for heart failure. Grade III or IV MR severity was present in 89%, with MR being primary in 90.3% of patients, and 10.7% had severe mitral stenosis.

Tendyne procedure survival was 98.1%, technical success was 94.2%, and valves were implanted in all patients. Emergency surgery or other intervention was required in 5.8%.

As co-presenter of the SUMMIT results, Vinod Thourani, MD, of the Piedmont Heart Institute in Atlanta, said at 30 days there was 6.8% all-cause mortality, all of it cardiovascular. There was one disabling stroke, one MI, no device thrombosis, and 21.4% major bleeding.

“At 1 month, there was less than grade 1 mitral regurgitation in all patients,” he reported, vs. 89% grade 3+/4+ at baseline. “At 1 month, it was an improvement in the NYHA classification to almost 70% in class I or II, which was improved from baseline of 26% in NYHA class I or II.”

Hemodynamic parameters all showed improvement, with a reduction in LVEF, LVEDV, and mitral valve gradient and increases in CO and forward stroke volume. There was no significant increase in LVOT gradient.

There was a small improvement in the KCCQ quality of life score from a baseline score of 49.2 to 52.3 at 30 days. “We’re expecting the KCCQ overall score to improve on 1 year follow up since the patients [are] still recovering from their thoracotomy incision,” Dr. Thourani predicted.

The primary endpoint will be evaluated at 1 year post procedure, he said at the meeting, sponsored by the Cardiovascular Research Foundation.
 

No good option

Designated discussant Joanna Chikwe, MD, chair of cardiac surgery at Cedars-Sinai Medical Center in Los Angeles, first thanked the presenters for their trial, saying, “What an absolute pleasure to be a mitral surgeon at a meeting where you’re presenting a solution for something that we find incredibly challenging. There’s no good transcatheter option for MAC. There’s no great surgical option for MAC.”

She noted the small size of the MAC cohort and asked what drove failure in patient screening, starting with 474 patients, identifying 120 who would be eligible, and enrolling 103 in the MAC cohort. The presenters identified neo-LVOT, the residual LVOT created after implanting the mitral valve prosthesis. Screening also eliminated patients with a too large or too small annulus.

Dr. Thourani said in Europe, surgeons have used anterior leaflet splitting before Tendyne, which may help to expand the population of eligible patients, but no leaflet modification was allowed in the SUMMIT trial.

Dr. Chikwe then pointed to the six deaths in the MAC arm and 11 deaths in the roll-in arm and asked about the mechanism of these deaths. “Was it [that] the 22% major bleeding is transapical? Really the Achilles heel of this procedure? Is this something that could become a transcatheter device?”

“We call it a transcatheter procedure, but it’s very much a surgical procedure,” Dr. Rogers answered. “And, you know, despite having great experienced sites...many surgeons don’t deal with the apex very much.” Furthermore, catheter insertion can lead to bleeding complications.

He noted that the roll-in patients were the first one or two cases at each site, and there have been improvements with site experience. The apical pads assist in hemostasis. He said the current design of the Tendyne catheter-delivered valve does not allow it to be adapted to a transfemoral transseptal approach.

Dr. Rogers is a consultant to and co-national principal investigator of the SUMMIT Pivotal Trial for Abbott. He is a consultant to Boston Scientific and a consultant/equity holder in Laminar. Dr. Thourani has received grant/research support from Abbott Vascular, Artivion, AtriCure, Boston Scientific, Croivalve, Edwards Lifesciences, JenaValve, Medtronic, and Trisol; consultant fees/honoraria from Abbott Vascular, Artivion, AtriCure, Boston Scientific, Croivalve, and Edwards Lifesciences; and has an executive role/ownership interest in DASI Simulations. Dr. Chikwe reports no relevant financial relationships. The SUMMIT trial was sponsored by Abbott.

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

TOPLINE:

Left atrial appendage closure was associated with about half as many disabling or fatal strokes and lower mortality after a stroke, compared with dual oral anticoagulant therapy in patients with atrial fibrillation (AFib), new observational research shows.

METHODOLOGY:

• The retrospective registry analysis included 447 adult patients with nonvalvular AFib, mean age 74 years, who were hospitalized with an ischemic stroke, 322 of whom were receiving direct oral anticoagulant (DOAC) therapy, mostly (84%) apixaban or rivaroxaban, and 125 were treated with left atrial appendage closure (LAAC), almost all (97%) with Watchman or Watchman-FLX devices.
• All patients received standard stroke care, monitoring, and treatment as well as physical therapy/rehabilitation.
• For the primary outcome, researchers used the modified Rankin Scale (mRS) to determine disabling (mRS score of 3-5) and fatal (mRS score of 6) strokes at discharge and at 3 months.
• The study adjusted for age, smoking, paroxysmal AFib, prior major bleeding, prior hemorrhagic stroke, medication adherence, and other risk factors.

TAKEAWAY:

• The incidence of disabling or fatal IS was significantly lower with LAAC versus with DOAC at discharge (38.3% vs. 70.3%; P < .001) and at 3 months (33.3% vs. 56.2%; P < .001), even though the LAAC group had more baseline comorbidity, for example, older age, more smokers, and more prior major bleeding.
• There was no significant difference in mortality between groups during hospitalization, but at 3 months, mortality was lower in the LAAC group (14.7% vs. 32.1%; P = .002).
• Multivariate linear regression analysis showed LAAC independently predicted more favorable mRS at discharge (2.8) and 3 months (1.4) (both P < .001) and was associated with less all-cause death at 3 months (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = .002).
• Including those that excluded the 14.4% of LAAC patients who also received DOAC therapy, sensitivity analyses patients who got reduced dose DOACs and nonadherent patients yielded nearly identical outcomes to the full cohort analysis.

IN PRACTICE:

“Despite a higher baseline risk profile, patients treated with LAAC who developed IS had better outcomes than those receiving DOAC prophylaxis,” the authors conclude, adding that several ongoing prospective trials could, “shed light on the mechanism(s) responsible for differences in stroke severity.”

SOURCE:

The study was conducted by Mohit K. Turagam, MD, Icahn School of Medicine at Mount Sinai, New York, and colleagues. It was published online in JACC: Clinical Electrophysiology.

LIMITATIONS:

Despite sensitivity analyses and adjustment for risk factors, selection bias, missing data, and other confounding factors could have affected outcomes. The study didn’t evaluate recurrent IS or type and intensity of rehabilitation on outcomes. Lack of imaging data comparing stroke infarct size and volume limits understanding of exact mechanism driving higher stroke severity with DOACs. Because patients who died before reaching hospital weren’t captured in the registry, the actual mortality may be higher than reported.

DISCLOSURES:

Dr. Turagam has served as a consultant for Biosense Webster and Sanofi.

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

TOPLINE:

Left atrial appendage closure was associated with about half as many disabling or fatal strokes and lower mortality after a stroke, compared with dual oral anticoagulant therapy in patients with atrial fibrillation (AFib), new observational research shows.

METHODOLOGY:

• The retrospective registry analysis included 447 adult patients with nonvalvular AFib, mean age 74 years, who were hospitalized with an ischemic stroke, 322 of whom were receiving direct oral anticoagulant (DOAC) therapy, mostly (84%) apixaban or rivaroxaban, and 125 were treated with left atrial appendage closure (LAAC), almost all (97%) with Watchman or Watchman-FLX devices.
• All patients received standard stroke care, monitoring, and treatment as well as physical therapy/rehabilitation.
• For the primary outcome, researchers used the modified Rankin Scale (mRS) to determine disabling (mRS score of 3-5) and fatal (mRS score of 6) strokes at discharge and at 3 months.
• The study adjusted for age, smoking, paroxysmal AFib, prior major bleeding, prior hemorrhagic stroke, medication adherence, and other risk factors.

TAKEAWAY:

• The incidence of disabling or fatal IS was significantly lower with LAAC versus with DOAC at discharge (38.3% vs. 70.3%; P < .001) and at 3 months (33.3% vs. 56.2%; P < .001), even though the LAAC group had more baseline comorbidity, for example, older age, more smokers, and more prior major bleeding.
• There was no significant difference in mortality between groups during hospitalization, but at 3 months, mortality was lower in the LAAC group (14.7% vs. 32.1%; P = .002).
• Multivariate linear regression analysis showed LAAC independently predicted more favorable mRS at discharge (2.8) and 3 months (1.4) (both P < .001) and was associated with less all-cause death at 3 months (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = .002).
• Including those that excluded the 14.4% of LAAC patients who also received DOAC therapy, sensitivity analyses patients who got reduced dose DOACs and nonadherent patients yielded nearly identical outcomes to the full cohort analysis.

IN PRACTICE:

“Despite a higher baseline risk profile, patients treated with LAAC who developed IS had better outcomes than those receiving DOAC prophylaxis,” the authors conclude, adding that several ongoing prospective trials could, “shed light on the mechanism(s) responsible for differences in stroke severity.”

SOURCE:

The study was conducted by Mohit K. Turagam, MD, Icahn School of Medicine at Mount Sinai, New York, and colleagues. It was published online in JACC: Clinical Electrophysiology.

LIMITATIONS:

Despite sensitivity analyses and adjustment for risk factors, selection bias, missing data, and other confounding factors could have affected outcomes. The study didn’t evaluate recurrent IS or type and intensity of rehabilitation on outcomes. Lack of imaging data comparing stroke infarct size and volume limits understanding of exact mechanism driving higher stroke severity with DOACs. Because patients who died before reaching hospital weren’t captured in the registry, the actual mortality may be higher than reported.

DISCLOSURES:

Dr. Turagam has served as a consultant for Biosense Webster and Sanofi.

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

TOPLINE:

Left atrial appendage closure was associated with about half as many disabling or fatal strokes and lower mortality after a stroke, compared with dual oral anticoagulant therapy in patients with atrial fibrillation (AFib), new observational research shows.

METHODOLOGY:

• The retrospective registry analysis included 447 adult patients with nonvalvular AFib, mean age 74 years, who were hospitalized with an ischemic stroke, 322 of whom were receiving direct oral anticoagulant (DOAC) therapy, mostly (84%) apixaban or rivaroxaban, and 125 were treated with left atrial appendage closure (LAAC), almost all (97%) with Watchman or Watchman-FLX devices.
• All patients received standard stroke care, monitoring, and treatment as well as physical therapy/rehabilitation.
• For the primary outcome, researchers used the modified Rankin Scale (mRS) to determine disabling (mRS score of 3-5) and fatal (mRS score of 6) strokes at discharge and at 3 months.
• The study adjusted for age, smoking, paroxysmal AFib, prior major bleeding, prior hemorrhagic stroke, medication adherence, and other risk factors.

TAKEAWAY:

• The incidence of disabling or fatal IS was significantly lower with LAAC versus with DOAC at discharge (38.3% vs. 70.3%; P < .001) and at 3 months (33.3% vs. 56.2%; P < .001), even though the LAAC group had more baseline comorbidity, for example, older age, more smokers, and more prior major bleeding.
• There was no significant difference in mortality between groups during hospitalization, but at 3 months, mortality was lower in the LAAC group (14.7% vs. 32.1%; P = .002).
• Multivariate linear regression analysis showed LAAC independently predicted more favorable mRS at discharge (2.8) and 3 months (1.4) (both P < .001) and was associated with less all-cause death at 3 months (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = .002).
• Including those that excluded the 14.4% of LAAC patients who also received DOAC therapy, sensitivity analyses patients who got reduced dose DOACs and nonadherent patients yielded nearly identical outcomes to the full cohort analysis.

IN PRACTICE:

“Despite a higher baseline risk profile, patients treated with LAAC who developed IS had better outcomes than those receiving DOAC prophylaxis,” the authors conclude, adding that several ongoing prospective trials could, “shed light on the mechanism(s) responsible for differences in stroke severity.”

SOURCE:

The study was conducted by Mohit K. Turagam, MD, Icahn School of Medicine at Mount Sinai, New York, and colleagues. It was published online in JACC: Clinical Electrophysiology.

LIMITATIONS:

Despite sensitivity analyses and adjustment for risk factors, selection bias, missing data, and other confounding factors could have affected outcomes. The study didn’t evaluate recurrent IS or type and intensity of rehabilitation on outcomes. Lack of imaging data comparing stroke infarct size and volume limits understanding of exact mechanism driving higher stroke severity with DOACs. Because patients who died before reaching hospital weren’t captured in the registry, the actual mortality may be higher than reported.

DISCLOSURES:

Dr. Turagam has served as a consultant for Biosense Webster and Sanofi.

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

For preventing rejection of cardiac transplants in children, the combination of everolimus and low-dose tacrolimus should now be considered an alternative to mycophenolate mofetil (MMF) plus standard-dose tacrolimus, according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.

Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.

Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.

In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
 

Everolimus- vs. MMF-based antirejection

The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m² every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).

In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).

The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).

Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
 

Numerical advantage for everolimus on efficacy

The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.

Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.

On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.

In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).

Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).

Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
 

Study supports safety of everolimus regimen

The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.

However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.

“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.

Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.

He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.

Early mortality based on infection “was not observed in our study,” he said.

The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.

Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,

Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.

For preventing rejection of cardiac transplants in children, the combination of everolimus and low-dose tacrolimus should now be considered an alternative to mycophenolate mofetil (MMF) plus standard-dose tacrolimus, according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.

Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.

Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.

In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
 

Everolimus- vs. MMF-based antirejection

The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m² every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).

In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).

The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).

Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
 

Numerical advantage for everolimus on efficacy

The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.

Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.

On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.

In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).

Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).

Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
 

Study supports safety of everolimus regimen

The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.

However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.

“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.

Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.

He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.

Early mortality based on infection “was not observed in our study,” he said.

The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.

Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,

Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.

For preventing rejection of cardiac transplants in children, the combination of everolimus and low-dose tacrolimus should now be considered an alternative to mycophenolate mofetil (MMF) plus standard-dose tacrolimus, according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.

Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.

Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.

In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
 

Everolimus- vs. MMF-based antirejection

The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m² every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).

In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).

The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).

Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
 

Numerical advantage for everolimus on efficacy

The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.

Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.

On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.

In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).

Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).

Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
 

Study supports safety of everolimus regimen

The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.

However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.

“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.

Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.

He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.

Early mortality based on infection “was not observed in our study,” he said.

The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.

Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,

Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.

PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.

“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.

AHA/Scott Morgan

Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.

They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.

Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
 

Trial results

The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*

He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).

The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.

The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”

Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
 

‘Novel’ for an AI trial

“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”

AHA/Scott Morgan

Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”

He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”

However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.

Dr. Lin and Dr. Nallamothu have no relevant disclosures.

*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.

PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.

“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.

AHA/Scott Morgan

Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.

They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.

Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
 

Trial results

The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*

He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).

The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.

The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”

Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
 

‘Novel’ for an AI trial

“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”

AHA/Scott Morgan

Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”

He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”

However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.

Dr. Lin and Dr. Nallamothu have no relevant disclosures.

*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.

PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.

“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.

AHA/Scott Morgan

Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.

They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.

Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
 

Trial results

The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*

He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).

The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.

The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”

Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
 

‘Novel’ for an AI trial

“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”

AHA/Scott Morgan

Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”

He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”

However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.

Dr. Lin and Dr. Nallamothu have no relevant disclosures.

*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.

PHILADELPHIA – Percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) reduces angina frequency, increases exercise capacity, and improves quality of life, results of a placebo-controlled, randomized trial show, confirming advantages that have never before been proven.

“The effect of PCI was immediate, sustained over 12 weeks, and consistent across all endpoints,” reported Christopher A. Rajkumar, MBBS, an interventional cardiology registrar at the Imperial College Healthcare Trust, London.

Results of the trial, ORBITA-2, were presented at the annual scientific sessions of the American Heart Association and simultaneously published online in the New England Journal of Medicine.

Symptom relief has long been a justification for PCI in patients with stable CAD, but the evidence has been derived from uncontrolled studies, Dr. Rajkumar said. However, the first ORBITA trial, which was also placebo controlled and randomized, failed to show benefit.

Dr. Rajkumar acknowledged that the benefit of PCI in ORBITA-2 was lower than previously reported in nonrandomized trials. He also noted that 59% of patients still had at least some angina symptoms following PCI.

Even though ORBITA-2 proves that PCI is better than no PCI, he agreed that well-informed patients, such as those who wish to avoid an invasive procedure, might still reasonably select antianginal medication over PCI. Current guidelines recommend PCI for patients with refractory angina despite medical therapy.

While Dr. Rajkumar was unwilling to speculate on how these data might change guidelines, he did say that patients with stable CAD and angina “now have a choice of two first-line evidence-based pathways.”
 

‘Remarkable’ trial

“ORBITA 2 is a rather remarkable trial because my surgical colleagues have been asking me for many decades whether PCI actually works,” said Martin B. Leon, MD, professor of medicine, Columbia University Irving Medical Center, New York. “Now I can say with confidence on the basis of a placebo-controlled trial that PCI certainly does have a favorable impact in patients with documented angina, severe coronary stenosis, and demonstrated ischemia.”

The key enrollment criteria for ORBITA-2 were angina, severe coronary stenosis in at least one vessel, and ischemia on stress imaging or invasive physiology. Unlike the previous ORBITA trial, which was limited to single-vessel disease and did not require objective evidence of ischemia, ORBITA 2 employed change in angina, rather than improved exercise capacity, as its primary endpoint.

Relative to sham PCI, patients randomly assigned to an interventional procedure had a more than twofold increase in the odds ratio of improved angina control (OR, 2.2; P < .001) based on a patient scoring system that captured angina symptoms as well as angina medication use on a smartphone application.  

The advantage of PCI over sham PCI was also significant for all secondary outcomes. These included a nearly fourfold greater (OR, 3.76; P < .001) likelihood of improvement in the Canadian Cardiovascular Society angina grade and a 1-minute increase (from 10 min. 40 seconds to 11 min. 40 seconds) in treadmill exercise time (P = .008).

On quality of life measured with the self-assessment questionnaire and the EQ-5D-5L, almost all endpoints were highly statistically significant in favor of PCI (typically on the level of P < .001).

The study had a bold design: At enrollment patients stopped all antianginal medications to undergo dobutamine echocardiography and other baseline tests. They were stopped again 2 weeks later, when patients were randomized.  

With a study protocol that enrolled patients off medication, “we intentionally diverged from the clinical guidelines,” Dr. Rajkumar said.

Of the 439 patients enrolled, 301 were randomly assigned at the end of the 2-week period, when patients were already sedated. Control patients remained sedated for at least 15 minutes. All 151 of those randomized to PCI and the 150 control patients were available for the intent-to-treat analysis at the end of 12 weeks.

The novel angina symptom burden score was created from daily angina episodes and units of daily antianginal medication captured on the smartphone app. On an ordinal scale, a score of 0 on any given day represented no anginal symptoms and no antianginal medication.

As angina severity or medication use increased, it raised the daily scores. If there was unacceptable angina (requiring the patient to be removed from the blind), acute coronary syndrome, or death, it produced the highest scores, which reached a maximum of 79.

The favorable OR for a lower symptom burden in the PCI group reflected a relative reduction in angina observed the first day after the procedure. Over the entire follow-up, more patients in the PCI group had an angina score of 0 and more of those who had angina did not take antianginal medications.

This objective evidence that PCI reduces symptoms and improves quality of life in patients with angina and stable CAD was met at the AHA late-breaking session with a sustained ovation.
 

ORBITA-2 addresses ORBITA criticisms

Connie N. Hess, MD, the AHA-invited discussant and an interventional cardiologist at the University of Colorado Medicine, Aurora, provided perspective on the differences between ORBITA 2 and ORBITA, which she said “addressed a fundamentally different hypothesis” by focusing on angina rather than exercise capacity.

Of the criticisms of the original ORBITA, which Dr. Hess noted was the first sham-controlled PCI trial ever conducted in stable CAD, one is that patients with multivessel disease were excluded, another was that objectively proven ischemia was not required, and a third was that the study of 6 weeks had a short duration.

“ORBITA 2 addressed many of these concerns,” Dr. Hess said, but, when noting that 80% of patients in the newer trial still had single vessel disease, she questioned whether the true effect of PCI for improving symptoms might still be underestimated.

ORBITA-2 was supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre, the Medical Research Council, NIHR, the British Heart Foundation, Philips, and St. Mary’s Coronary Flow Trust. Dr. Rajkumar reported relevant financial relationships. Dr. Leon reported financial relationships with Abbott Vascular, Anteris, Boston Scientific, Edwards Lifesciences, Foldax, and Medtronic. Dr. Hess has financial relationships with more than 20 pharmaceutical companies, but none related specifically to this presentation.

PHILADELPHIA – Percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) reduces angina frequency, increases exercise capacity, and improves quality of life, results of a placebo-controlled, randomized trial show, confirming advantages that have never before been proven.

“The effect of PCI was immediate, sustained over 12 weeks, and consistent across all endpoints,” reported Christopher A. Rajkumar, MBBS, an interventional cardiology registrar at the Imperial College Healthcare Trust, London.

Results of the trial, ORBITA-2, were presented at the annual scientific sessions of the American Heart Association and simultaneously published online in the New England Journal of Medicine.

Symptom relief has long been a justification for PCI in patients with stable CAD, but the evidence has been derived from uncontrolled studies, Dr. Rajkumar said. However, the first ORBITA trial, which was also placebo controlled and randomized, failed to show benefit.

Dr. Rajkumar acknowledged that the benefit of PCI in ORBITA-2 was lower than previously reported in nonrandomized trials. He also noted that 59% of patients still had at least some angina symptoms following PCI.

Even though ORBITA-2 proves that PCI is better than no PCI, he agreed that well-informed patients, such as those who wish to avoid an invasive procedure, might still reasonably select antianginal medication over PCI. Current guidelines recommend PCI for patients with refractory angina despite medical therapy.

While Dr. Rajkumar was unwilling to speculate on how these data might change guidelines, he did say that patients with stable CAD and angina “now have a choice of two first-line evidence-based pathways.”
 

‘Remarkable’ trial

“ORBITA 2 is a rather remarkable trial because my surgical colleagues have been asking me for many decades whether PCI actually works,” said Martin B. Leon, MD, professor of medicine, Columbia University Irving Medical Center, New York. “Now I can say with confidence on the basis of a placebo-controlled trial that PCI certainly does have a favorable impact in patients with documented angina, severe coronary stenosis, and demonstrated ischemia.”

The key enrollment criteria for ORBITA-2 were angina, severe coronary stenosis in at least one vessel, and ischemia on stress imaging or invasive physiology. Unlike the previous ORBITA trial, which was limited to single-vessel disease and did not require objective evidence of ischemia, ORBITA 2 employed change in angina, rather than improved exercise capacity, as its primary endpoint.

Relative to sham PCI, patients randomly assigned to an interventional procedure had a more than twofold increase in the odds ratio of improved angina control (OR, 2.2; P < .001) based on a patient scoring system that captured angina symptoms as well as angina medication use on a smartphone application.  

The advantage of PCI over sham PCI was also significant for all secondary outcomes. These included a nearly fourfold greater (OR, 3.76; P < .001) likelihood of improvement in the Canadian Cardiovascular Society angina grade and a 1-minute increase (from 10 min. 40 seconds to 11 min. 40 seconds) in treadmill exercise time (P = .008).

On quality of life measured with the self-assessment questionnaire and the EQ-5D-5L, almost all endpoints were highly statistically significant in favor of PCI (typically on the level of P < .001).

The study had a bold design: At enrollment patients stopped all antianginal medications to undergo dobutamine echocardiography and other baseline tests. They were stopped again 2 weeks later, when patients were randomized.  

With a study protocol that enrolled patients off medication, “we intentionally diverged from the clinical guidelines,” Dr. Rajkumar said.

Of the 439 patients enrolled, 301 were randomly assigned at the end of the 2-week period, when patients were already sedated. Control patients remained sedated for at least 15 minutes. All 151 of those randomized to PCI and the 150 control patients were available for the intent-to-treat analysis at the end of 12 weeks.

The novel angina symptom burden score was created from daily angina episodes and units of daily antianginal medication captured on the smartphone app. On an ordinal scale, a score of 0 on any given day represented no anginal symptoms and no antianginal medication.

As angina severity or medication use increased, it raised the daily scores. If there was unacceptable angina (requiring the patient to be removed from the blind), acute coronary syndrome, or death, it produced the highest scores, which reached a maximum of 79.

The favorable OR for a lower symptom burden in the PCI group reflected a relative reduction in angina observed the first day after the procedure. Over the entire follow-up, more patients in the PCI group had an angina score of 0 and more of those who had angina did not take antianginal medications.

This objective evidence that PCI reduces symptoms and improves quality of life in patients with angina and stable CAD was met at the AHA late-breaking session with a sustained ovation.
 

ORBITA-2 addresses ORBITA criticisms

Connie N. Hess, MD, the AHA-invited discussant and an interventional cardiologist at the University of Colorado Medicine, Aurora, provided perspective on the differences between ORBITA 2 and ORBITA, which she said “addressed a fundamentally different hypothesis” by focusing on angina rather than exercise capacity.

Of the criticisms of the original ORBITA, which Dr. Hess noted was the first sham-controlled PCI trial ever conducted in stable CAD, one is that patients with multivessel disease were excluded, another was that objectively proven ischemia was not required, and a third was that the study of 6 weeks had a short duration.

“ORBITA 2 addressed many of these concerns,” Dr. Hess said, but, when noting that 80% of patients in the newer trial still had single vessel disease, she questioned whether the true effect of PCI for improving symptoms might still be underestimated.

ORBITA-2 was supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre, the Medical Research Council, NIHR, the British Heart Foundation, Philips, and St. Mary’s Coronary Flow Trust. Dr. Rajkumar reported relevant financial relationships. Dr. Leon reported financial relationships with Abbott Vascular, Anteris, Boston Scientific, Edwards Lifesciences, Foldax, and Medtronic. Dr. Hess has financial relationships with more than 20 pharmaceutical companies, but none related specifically to this presentation.

PHILADELPHIA – Percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) reduces angina frequency, increases exercise capacity, and improves quality of life, results of a placebo-controlled, randomized trial show, confirming advantages that have never before been proven.

“The effect of PCI was immediate, sustained over 12 weeks, and consistent across all endpoints,” reported Christopher A. Rajkumar, MBBS, an interventional cardiology registrar at the Imperial College Healthcare Trust, London.

Results of the trial, ORBITA-2, were presented at the annual scientific sessions of the American Heart Association and simultaneously published online in the New England Journal of Medicine.

Symptom relief has long been a justification for PCI in patients with stable CAD, but the evidence has been derived from uncontrolled studies, Dr. Rajkumar said. However, the first ORBITA trial, which was also placebo controlled and randomized, failed to show benefit.

Dr. Rajkumar acknowledged that the benefit of PCI in ORBITA-2 was lower than previously reported in nonrandomized trials. He also noted that 59% of patients still had at least some angina symptoms following PCI.

Even though ORBITA-2 proves that PCI is better than no PCI, he agreed that well-informed patients, such as those who wish to avoid an invasive procedure, might still reasonably select antianginal medication over PCI. Current guidelines recommend PCI for patients with refractory angina despite medical therapy.

While Dr. Rajkumar was unwilling to speculate on how these data might change guidelines, he did say that patients with stable CAD and angina “now have a choice of two first-line evidence-based pathways.”
 

‘Remarkable’ trial

“ORBITA 2 is a rather remarkable trial because my surgical colleagues have been asking me for many decades whether PCI actually works,” said Martin B. Leon, MD, professor of medicine, Columbia University Irving Medical Center, New York. “Now I can say with confidence on the basis of a placebo-controlled trial that PCI certainly does have a favorable impact in patients with documented angina, severe coronary stenosis, and demonstrated ischemia.”

The key enrollment criteria for ORBITA-2 were angina, severe coronary stenosis in at least one vessel, and ischemia on stress imaging or invasive physiology. Unlike the previous ORBITA trial, which was limited to single-vessel disease and did not require objective evidence of ischemia, ORBITA 2 employed change in angina, rather than improved exercise capacity, as its primary endpoint.

Relative to sham PCI, patients randomly assigned to an interventional procedure had a more than twofold increase in the odds ratio of improved angina control (OR, 2.2; P < .001) based on a patient scoring system that captured angina symptoms as well as angina medication use on a smartphone application.  

The advantage of PCI over sham PCI was also significant for all secondary outcomes. These included a nearly fourfold greater (OR, 3.76; P < .001) likelihood of improvement in the Canadian Cardiovascular Society angina grade and a 1-minute increase (from 10 min. 40 seconds to 11 min. 40 seconds) in treadmill exercise time (P = .008).

On quality of life measured with the self-assessment questionnaire and the EQ-5D-5L, almost all endpoints were highly statistically significant in favor of PCI (typically on the level of P < .001).

The study had a bold design: At enrollment patients stopped all antianginal medications to undergo dobutamine echocardiography and other baseline tests. They were stopped again 2 weeks later, when patients were randomized.  

With a study protocol that enrolled patients off medication, “we intentionally diverged from the clinical guidelines,” Dr. Rajkumar said.

Of the 439 patients enrolled, 301 were randomly assigned at the end of the 2-week period, when patients were already sedated. Control patients remained sedated for at least 15 minutes. All 151 of those randomized to PCI and the 150 control patients were available for the intent-to-treat analysis at the end of 12 weeks.

The novel angina symptom burden score was created from daily angina episodes and units of daily antianginal medication captured on the smartphone app. On an ordinal scale, a score of 0 on any given day represented no anginal symptoms and no antianginal medication.

As angina severity or medication use increased, it raised the daily scores. If there was unacceptable angina (requiring the patient to be removed from the blind), acute coronary syndrome, or death, it produced the highest scores, which reached a maximum of 79.

The favorable OR for a lower symptom burden in the PCI group reflected a relative reduction in angina observed the first day after the procedure. Over the entire follow-up, more patients in the PCI group had an angina score of 0 and more of those who had angina did not take antianginal medications.

This objective evidence that PCI reduces symptoms and improves quality of life in patients with angina and stable CAD was met at the AHA late-breaking session with a sustained ovation.
 

ORBITA-2 addresses ORBITA criticisms

Connie N. Hess, MD, the AHA-invited discussant and an interventional cardiologist at the University of Colorado Medicine, Aurora, provided perspective on the differences between ORBITA 2 and ORBITA, which she said “addressed a fundamentally different hypothesis” by focusing on angina rather than exercise capacity.

Of the criticisms of the original ORBITA, which Dr. Hess noted was the first sham-controlled PCI trial ever conducted in stable CAD, one is that patients with multivessel disease were excluded, another was that objectively proven ischemia was not required, and a third was that the study of 6 weeks had a short duration.

“ORBITA 2 addressed many of these concerns,” Dr. Hess said, but, when noting that 80% of patients in the newer trial still had single vessel disease, she questioned whether the true effect of PCI for improving symptoms might still be underestimated.

ORBITA-2 was supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre, the Medical Research Council, NIHR, the British Heart Foundation, Philips, and St. Mary’s Coronary Flow Trust. Dr. Rajkumar reported relevant financial relationships. Dr. Leon reported financial relationships with Abbott Vascular, Anteris, Boston Scientific, Edwards Lifesciences, Foldax, and Medtronic. Dr. Hess has financial relationships with more than 20 pharmaceutical companies, but none related specifically to this presentation.

TOPLINE:

About 83% of adults with aortic valve disease who underwent the Ross procedure, which uses a valve substitute that preserves mobility of the neo-aortic root, are still alive at 25 years postprocedure, a survival rate equivalent to that of the general population, results of a new study show. The need for reintervention in these patients is low.

METHODOLOGY:

• The study was a post hoc analysis of a randomized clinical trial that showed superior survival, freedom from reoperation, and quality of life at 10 years for patients who received the Ross procedure, compared with those who got homograft root replacement.
• This new analysis included 108 patients, median age 38 years and mostly male and of British origin, who underwent the Ross procedure. Of these, 45% had aortic regurgitation (AR) as the main hemodynamic lesion.
• The primary outcome was long-term survival, compared with an age-, sex-, and country of origin–matched general U.K. population using a novel, patient-level matching strategy. Secondary outcomes included freedom from any valve-related reintervention, autograft reintervention, or homograft reintervention.

TAKEAWAY:

• Survival at 25 years was 83.0% (95% confidence interval, 75.5%-91.2%), representing a relative survival of 99.1% (95% CI, 91.8%-100%), compared with the matched general population (survival in general population was 83.7%).
• At 25 years, freedom from any Ross-related reintervention was 71.1% (95% CI, 61.6%-82.0%); freedom from autograft reintervention was 80.3% (95% CI, 71.9%-89.6%); and freedom from homograft reintervention was 86.3% (95% CI, 79.0%-94.3%).
• There was no increased hazard for autograft deterioration in patients presenting with versus without preoperative AR, an important finding since it has been suggested Ross procedure benefits may not extend fully to patients with preoperative AR, said the authors.
• 86% of patients had New York Heart Association class I or II status at the latest clinical follow-up (approaching 25 years).

IN PRACTICE:

This study shows the Ross procedure “provided excellent survival into the third decade after surgery,” with the new data further supporting “the unique benefits” of the valve substitute in adults, the authors conclude.

Authors of an accompanying editorial, Tsuyoshi Kaneko, MD, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, and Maral Ouzounian, MD, PhD, Peter Munk Cardiac Centre, Division of Cardiac Surgery, University Health Network, University of Toronto, write that the new evidence suggests the Ross procedure is “a truly attractive option in younger patients with long life expectancy.” However, they note that aortic regurgitation in the cohort worsened over time, potentially leading to late reinterventions; echocardiographic follow-up was available in only 71% of patients; and generalizing the Ross procedure to a broader group of surgeons is challenging.

SOURCE:

The study was conducted by Maximiliaan L. Notenboom, BSc, department of cardiothoracic surgery, Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis reflects a single-surgeon experience, so it’s difficult to extrapolate the results, although the operative steps involved in the Ross procedure have now been clearly delineated, making the operation reproducible. The duration of echocardiographic follow-up was shorter and less complete than the clinical follow-up. Outcomes of the cohort that underwent homograft procedures in the randomized clinical trial were not reported, but since that procedure has nearly disappeared from practice, reporting on its long-term outcomes would be of limited clinical significance.

DISCLOSURES:

Mr. Notenboom has disclosed no relevant financial relationships. Co-author Fabio De Robertis, MD, department of cardiothoracic surgery and transplantation, Royal Brompton & Harefield Hospitals, London, received nonfinancial support from Edwards Lifescience for travel and personal fees from Bristol Myers Squibb for consulting outside the submitted work, and has a service agreement with Medtronic U.K., which paid a fee to the Royal Brompton & Harefield Hospitals Charity Fund.

Editorial co-author Kaneko received personal fees from Edwards Lifesciences, Medtronic, Abbott, and Johnson & Johnson outside the submitted work; Ouzounian received personal fees from Medtronic, Edwards Lifesciences, and Terumo Aortic outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

About 83% of adults with aortic valve disease who underwent the Ross procedure, which uses a valve substitute that preserves mobility of the neo-aortic root, are still alive at 25 years postprocedure, a survival rate equivalent to that of the general population, results of a new study show. The need for reintervention in these patients is low.

METHODOLOGY:

• The study was a post hoc analysis of a randomized clinical trial that showed superior survival, freedom from reoperation, and quality of life at 10 years for patients who received the Ross procedure, compared with those who got homograft root replacement.
• This new analysis included 108 patients, median age 38 years and mostly male and of British origin, who underwent the Ross procedure. Of these, 45% had aortic regurgitation (AR) as the main hemodynamic lesion.
• The primary outcome was long-term survival, compared with an age-, sex-, and country of origin–matched general U.K. population using a novel, patient-level matching strategy. Secondary outcomes included freedom from any valve-related reintervention, autograft reintervention, or homograft reintervention.

TAKEAWAY:

• Survival at 25 years was 83.0% (95% confidence interval, 75.5%-91.2%), representing a relative survival of 99.1% (95% CI, 91.8%-100%), compared with the matched general population (survival in general population was 83.7%).
• At 25 years, freedom from any Ross-related reintervention was 71.1% (95% CI, 61.6%-82.0%); freedom from autograft reintervention was 80.3% (95% CI, 71.9%-89.6%); and freedom from homograft reintervention was 86.3% (95% CI, 79.0%-94.3%).
• There was no increased hazard for autograft deterioration in patients presenting with versus without preoperative AR, an important finding since it has been suggested Ross procedure benefits may not extend fully to patients with preoperative AR, said the authors.
• 86% of patients had New York Heart Association class I or II status at the latest clinical follow-up (approaching 25 years).

IN PRACTICE:

This study shows the Ross procedure “provided excellent survival into the third decade after surgery,” with the new data further supporting “the unique benefits” of the valve substitute in adults, the authors conclude.

Authors of an accompanying editorial, Tsuyoshi Kaneko, MD, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, and Maral Ouzounian, MD, PhD, Peter Munk Cardiac Centre, Division of Cardiac Surgery, University Health Network, University of Toronto, write that the new evidence suggests the Ross procedure is “a truly attractive option in younger patients with long life expectancy.” However, they note that aortic regurgitation in the cohort worsened over time, potentially leading to late reinterventions; echocardiographic follow-up was available in only 71% of patients; and generalizing the Ross procedure to a broader group of surgeons is challenging.

SOURCE:

The study was conducted by Maximiliaan L. Notenboom, BSc, department of cardiothoracic surgery, Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis reflects a single-surgeon experience, so it’s difficult to extrapolate the results, although the operative steps involved in the Ross procedure have now been clearly delineated, making the operation reproducible. The duration of echocardiographic follow-up was shorter and less complete than the clinical follow-up. Outcomes of the cohort that underwent homograft procedures in the randomized clinical trial were not reported, but since that procedure has nearly disappeared from practice, reporting on its long-term outcomes would be of limited clinical significance.

DISCLOSURES:

Mr. Notenboom has disclosed no relevant financial relationships. Co-author Fabio De Robertis, MD, department of cardiothoracic surgery and transplantation, Royal Brompton & Harefield Hospitals, London, received nonfinancial support from Edwards Lifescience for travel and personal fees from Bristol Myers Squibb for consulting outside the submitted work, and has a service agreement with Medtronic U.K., which paid a fee to the Royal Brompton & Harefield Hospitals Charity Fund.

Editorial co-author Kaneko received personal fees from Edwards Lifesciences, Medtronic, Abbott, and Johnson & Johnson outside the submitted work; Ouzounian received personal fees from Medtronic, Edwards Lifesciences, and Terumo Aortic outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

About 83% of adults with aortic valve disease who underwent the Ross procedure, which uses a valve substitute that preserves mobility of the neo-aortic root, are still alive at 25 years postprocedure, a survival rate equivalent to that of the general population, results of a new study show. The need for reintervention in these patients is low.

METHODOLOGY:

• The study was a post hoc analysis of a randomized clinical trial that showed superior survival, freedom from reoperation, and quality of life at 10 years for patients who received the Ross procedure, compared with those who got homograft root replacement.
• This new analysis included 108 patients, median age 38 years and mostly male and of British origin, who underwent the Ross procedure. Of these, 45% had aortic regurgitation (AR) as the main hemodynamic lesion.
• The primary outcome was long-term survival, compared with an age-, sex-, and country of origin–matched general U.K. population using a novel, patient-level matching strategy. Secondary outcomes included freedom from any valve-related reintervention, autograft reintervention, or homograft reintervention.

TAKEAWAY:

• Survival at 25 years was 83.0% (95% confidence interval, 75.5%-91.2%), representing a relative survival of 99.1% (95% CI, 91.8%-100%), compared with the matched general population (survival in general population was 83.7%).
• At 25 years, freedom from any Ross-related reintervention was 71.1% (95% CI, 61.6%-82.0%); freedom from autograft reintervention was 80.3% (95% CI, 71.9%-89.6%); and freedom from homograft reintervention was 86.3% (95% CI, 79.0%-94.3%).
• There was no increased hazard for autograft deterioration in patients presenting with versus without preoperative AR, an important finding since it has been suggested Ross procedure benefits may not extend fully to patients with preoperative AR, said the authors.
• 86% of patients had New York Heart Association class I or II status at the latest clinical follow-up (approaching 25 years).

IN PRACTICE:

This study shows the Ross procedure “provided excellent survival into the third decade after surgery,” with the new data further supporting “the unique benefits” of the valve substitute in adults, the authors conclude.

Authors of an accompanying editorial, Tsuyoshi Kaneko, MD, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, and Maral Ouzounian, MD, PhD, Peter Munk Cardiac Centre, Division of Cardiac Surgery, University Health Network, University of Toronto, write that the new evidence suggests the Ross procedure is “a truly attractive option in younger patients with long life expectancy.” However, they note that aortic regurgitation in the cohort worsened over time, potentially leading to late reinterventions; echocardiographic follow-up was available in only 71% of patients; and generalizing the Ross procedure to a broader group of surgeons is challenging.

SOURCE:

The study was conducted by Maximiliaan L. Notenboom, BSc, department of cardiothoracic surgery, Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis reflects a single-surgeon experience, so it’s difficult to extrapolate the results, although the operative steps involved in the Ross procedure have now been clearly delineated, making the operation reproducible. The duration of echocardiographic follow-up was shorter and less complete than the clinical follow-up. Outcomes of the cohort that underwent homograft procedures in the randomized clinical trial were not reported, but since that procedure has nearly disappeared from practice, reporting on its long-term outcomes would be of limited clinical significance.

DISCLOSURES:

Mr. Notenboom has disclosed no relevant financial relationships. Co-author Fabio De Robertis, MD, department of cardiothoracic surgery and transplantation, Royal Brompton & Harefield Hospitals, London, received nonfinancial support from Edwards Lifescience for travel and personal fees from Bristol Myers Squibb for consulting outside the submitted work, and has a service agreement with Medtronic U.K., which paid a fee to the Royal Brompton & Harefield Hospitals Charity Fund.

Editorial co-author Kaneko received personal fees from Edwards Lifesciences, Medtronic, Abbott, and Johnson & Johnson outside the submitted work; Ouzounian received personal fees from Medtronic, Edwards Lifesciences, and Terumo Aortic outside the submitted work.

A version of this article appeared on Medscape.com.

SAN FRANCISCO – Stopping aspirin within 1 month of implanting a drug-eluting stent (DES) for acute coronary syndrome (ACS) followed by ticagrelor monotherapy was shown to be noninferior to 12 months of dual antiplatelet therapy (DAPT) in net adverse cardiovascular and bleeding events in the T-PASS trial.

“Less than 1 month of DAPT followed by ticagrelor monotherapy met a noninferiority threshold and provided evidence of superiority to 12 months of ticagrelor-based DAPT for a 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily due to a significant reduction in bleeding events,” senior author Myeong-Ki Hong, MD, PhD, Yonsei University, Seoul, Korea, told attendees at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

“This study provides evidence that stopping aspirin within 1 month after implantation of drug-eluting stents for ticagrelor monotherapy is a reasonable alternative to 12-month DAPT as for adverse cardiovascular and bleeding events,” Dr. Hong concluded.

The study was published in Circulation ahead of print to coincide with the presentation.
 

Three months to 1 month

Previous trials (TICO and TWILIGHT) have shown that ticagrelor monotherapy after 3 months of DAPT can be safe and effectively prevent ischemic events after percutaneous coronary intervention (PCI) in ACS or high-risk PCI patients.

The current study aimed to investigate whether ticagrelor monotherapy after less than 1 month of DAPT was noninferior to 12 months of ticagrelor-based DAPT for preventing adverse cardiovascular and bleeding events in patients with ACS undergoing PCI with a DES implant.

T-PASS, carried out at 24 centers in Korea, enrolled ACS patients aged 19 years or older who received an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik). They were randomized 1:1 to ticagrelor monotherapy after less than 1 month of DAPT (n = 1,426) or to ticagrelor-based DAPT for 12 months (n = 1,424).

The primary outcome measure was net adverse clinical events (NACE) at 12 months, consisting of major bleeding plus major adverse cardiovascular events. All patients were included in the intention-to-treat analysis.

The study could enroll patients aged 19-80 years. It excluded anyone with active bleeding, at increased risk for bleeding, with anemia (hemoglobin ≤ 8 g/dL), platelets less than 100,000/mcL, need for oral anticoagulation therapy, current or potential pregnancy, or a life expectancy less than 1 year.

Baseline characteristics of the two groups were well balanced. The extended monotherapy and DAPT arms had an average age of 61 ± 10 years, were 84% and 83% male and had diabetes mellitus in 30% and 29%, respectively, with 74% of each group admitted via the emergency room. ST-elevation myocardial infarction occurred in 40% and 41% of patients in each group, respectively.

Results showed that stopping aspirin early was noninferior and possibly superior to 12 months of DAPT.

For the 12-month clinical outcome, fewer patients in the less than 1 month DAPT followed by ticagrelor monotherapy arm reached the primary clinical endpoint of NACE versus the ticagrelor-based 12-month DAPT arm, both in terms of noninferiority (P < .001) and superiority (P = .002). Similar results were found for the 1-month landmark analyses.

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

SAN FRANCISCO – Stopping aspirin within 1 month of implanting a drug-eluting stent (DES) for acute coronary syndrome (ACS) followed by ticagrelor monotherapy was shown to be noninferior to 12 months of dual antiplatelet therapy (DAPT) in net adverse cardiovascular and bleeding events in the T-PASS trial.

“Less than 1 month of DAPT followed by ticagrelor monotherapy met a noninferiority threshold and provided evidence of superiority to 12 months of ticagrelor-based DAPT for a 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily due to a significant reduction in bleeding events,” senior author Myeong-Ki Hong, MD, PhD, Yonsei University, Seoul, Korea, told attendees at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

“This study provides evidence that stopping aspirin within 1 month after implantation of drug-eluting stents for ticagrelor monotherapy is a reasonable alternative to 12-month DAPT as for adverse cardiovascular and bleeding events,” Dr. Hong concluded.

The study was published in Circulation ahead of print to coincide with the presentation.
 

Three months to 1 month

Previous trials (TICO and TWILIGHT) have shown that ticagrelor monotherapy after 3 months of DAPT can be safe and effectively prevent ischemic events after percutaneous coronary intervention (PCI) in ACS or high-risk PCI patients.

The current study aimed to investigate whether ticagrelor monotherapy after less than 1 month of DAPT was noninferior to 12 months of ticagrelor-based DAPT for preventing adverse cardiovascular and bleeding events in patients with ACS undergoing PCI with a DES implant.

T-PASS, carried out at 24 centers in Korea, enrolled ACS patients aged 19 years or older who received an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik). They were randomized 1:1 to ticagrelor monotherapy after less than 1 month of DAPT (n = 1,426) or to ticagrelor-based DAPT for 12 months (n = 1,424).

The primary outcome measure was net adverse clinical events (NACE) at 12 months, consisting of major bleeding plus major adverse cardiovascular events. All patients were included in the intention-to-treat analysis.

The study could enroll patients aged 19-80 years. It excluded anyone with active bleeding, at increased risk for bleeding, with anemia (hemoglobin ≤ 8 g/dL), platelets less than 100,000/mcL, need for oral anticoagulation therapy, current or potential pregnancy, or a life expectancy less than 1 year.

Baseline characteristics of the two groups were well balanced. The extended monotherapy and DAPT arms had an average age of 61 ± 10 years, were 84% and 83% male and had diabetes mellitus in 30% and 29%, respectively, with 74% of each group admitted via the emergency room. ST-elevation myocardial infarction occurred in 40% and 41% of patients in each group, respectively.

Results showed that stopping aspirin early was noninferior and possibly superior to 12 months of DAPT.

For the 12-month clinical outcome, fewer patients in the less than 1 month DAPT followed by ticagrelor monotherapy arm reached the primary clinical endpoint of NACE versus the ticagrelor-based 12-month DAPT arm, both in terms of noninferiority (P < .001) and superiority (P = .002). Similar results were found for the 1-month landmark analyses.

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

SAN FRANCISCO – Stopping aspirin within 1 month of implanting a drug-eluting stent (DES) for acute coronary syndrome (ACS) followed by ticagrelor monotherapy was shown to be noninferior to 12 months of dual antiplatelet therapy (DAPT) in net adverse cardiovascular and bleeding events in the T-PASS trial.

“Less than 1 month of DAPT followed by ticagrelor monotherapy met a noninferiority threshold and provided evidence of superiority to 12 months of ticagrelor-based DAPT for a 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily due to a significant reduction in bleeding events,” senior author Myeong-Ki Hong, MD, PhD, Yonsei University, Seoul, Korea, told attendees at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

“This study provides evidence that stopping aspirin within 1 month after implantation of drug-eluting stents for ticagrelor monotherapy is a reasonable alternative to 12-month DAPT as for adverse cardiovascular and bleeding events,” Dr. Hong concluded.

The study was published in Circulation ahead of print to coincide with the presentation.
 

Three months to 1 month

Previous trials (TICO and TWILIGHT) have shown that ticagrelor monotherapy after 3 months of DAPT can be safe and effectively prevent ischemic events after percutaneous coronary intervention (PCI) in ACS or high-risk PCI patients.

The current study aimed to investigate whether ticagrelor monotherapy after less than 1 month of DAPT was noninferior to 12 months of ticagrelor-based DAPT for preventing adverse cardiovascular and bleeding events in patients with ACS undergoing PCI with a DES implant.

T-PASS, carried out at 24 centers in Korea, enrolled ACS patients aged 19 years or older who received an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik). They were randomized 1:1 to ticagrelor monotherapy after less than 1 month of DAPT (n = 1,426) or to ticagrelor-based DAPT for 12 months (n = 1,424).

The primary outcome measure was net adverse clinical events (NACE) at 12 months, consisting of major bleeding plus major adverse cardiovascular events. All patients were included in the intention-to-treat analysis.

The study could enroll patients aged 19-80 years. It excluded anyone with active bleeding, at increased risk for bleeding, with anemia (hemoglobin ≤ 8 g/dL), platelets less than 100,000/mcL, need for oral anticoagulation therapy, current or potential pregnancy, or a life expectancy less than 1 year.

Baseline characteristics of the two groups were well balanced. The extended monotherapy and DAPT arms had an average age of 61 ± 10 years, were 84% and 83% male and had diabetes mellitus in 30% and 29%, respectively, with 74% of each group admitted via the emergency room. ST-elevation myocardial infarction occurred in 40% and 41% of patients in each group, respectively.

Results showed that stopping aspirin early was noninferior and possibly superior to 12 months of DAPT.

For the 12-month clinical outcome, fewer patients in the less than 1 month DAPT followed by ticagrelor monotherapy arm reached the primary clinical endpoint of NACE versus the ticagrelor-based 12-month DAPT arm, both in terms of noninferiority (P < .001) and superiority (P = .002). Similar results were found for the 1-month landmark analyses.

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