Patrice Wendling

CHICAGO – A randomized trial suggests resistance exercise promotes better sleep than other workouts among inactive adults, particularly those who are poor sleepers.

“We thought resistance exercise would be somewhere in the same neighborhood as aerobic exercise or that maybe combined exercise would be a little bit better but, no, it was consistently resistance exercise, on its own, that seemed to show the most benefits across the board,” Angelique Brellenthin, PhD, told this news organization.

The results were presented at the recent Epidemiology, Prevention/Lifestyle & Cardiometabolic Health meeting sponsored by the American Heart Association.

Even before the pandemic and bedtime “doom scrolling” took hold, research showed that a third of Americans regularly get less than 7 hours of sleep. The AHA recommends aerobic exercise to improve sleep and promote cardiovascular health, yet little is known on how it compares with other types of exercise in the general population, she said.

Dr. Brellenthin and coinvestigator Duck-chul Lee, PhD, both of Iowa State University in Ames, recruited 406 inactive adults, aged 35-70 years, who had obesity or overweight (mean body mass index, 31.2 kg/m²) and had elevated or stage 1 hypertension and randomly assigned them to no exercise or 60 minutes of supervised aerobic, resistance, or combination exercise three times per week for 12 months.

The aerobic exercise group could choose among treadmills, upright or recumbent bikes, and ellipticals, and the participants had their heart rate monitored to ensure they were continuously getting moderate- to vigorous-intensity exercise.

The resistance exercise group performed three sets of 8-16 repetitions at 50%-80% of their one-rep maximum on 12 resistance machines: a leg press, chest press, lat pulldown, leg curl, leg extension, biceps curl, triceps pushdown, shoulder press, abdominal crunch, lower back extension, torso rotation, and hip abduction.

The combination group did 30 minutes of aerobic exercise at moderate to vigorous intensity, and then two sets of 8-16 repetitions of resistance exercise on 9 machines instead of 12.

Exercise adherence over the year was 84%, 77%, and 85%, respectively.

Participants also completed the Pittsburgh Sleep Quality Index (PSQI) at baseline and 12 months. Among the 386 participants (53% women) with evaluable data, 35% had poor-quality sleep, as indicated by a global PSQI score of more than 5, and 42% regularly slept less than 7 hours per night.

In adjusted analyses, sleep duration at 12 months, on average, increased by 13 minutes in the resistance-exercise group (P = .009), decreased by 0.6 minute in the aerobic-exercise group, and increased by 2 minutes in the combined-exercise group and by 4 minutes in the control group.

Among participants who got less than 7 hours of sleep at baseline, however, sleep duration increased by 40 minutes (P < .0001), compared with increases of 23 minutes in the aerobic group, 17 minutes in the combined group, and 15 minutes in the control group.

Overall sleep efficiency, or the ratio of total sleep time to time in bed, improved in the resistance (P = .0005) and combined (P = .03) exercise groups, but not in the aerobic or control groups.

Sleep latency, or the time needed to fall asleep, decreased by 3 minutes in the resistance-exercise group, with no notable changes in the other groups.

Sleep quality and the number of sleep disturbances improved in all groups, including the control group. This could be due to simply being part of a health intervention, which included a month of lifestyle education classes, Dr. Brellenthin suggested.

It’s unclear why the aerobic-exercise group didn’t show greater gains, given the wealth of research showing it improves sleep, she said, but it had fewer poor sleepers at baseline than the resistance group (33% vs. 42%). “So it may be that people who were already getting good sleep didn’t have much room to improve.”

Among the poor-quality sleepers at baseline, resistance exercise significantly improved sleep quality (-2.4 vs. -1.0 points; P = .009) and duration (+36 vs. +3 minutes; P = .02), compared with the control group. It also improved sleep efficiency by 9.0%, compared with 0.9% in the control group (P = .002) and 8.0% for the combined-exercise group (P = .01).

“For a lot of people who know their sleep could be a bit better, this could be a place to start without resorting to medications, if they wanted to focus on a lifestyle intervention,” Dr. Brellenthin said.

It’s not fully understood how resistance exercise improves sleep, but it might contribute to better overall mental health and it might enhance the synthesis and release of certain hormones, such as testosterone and human growth hormone, which are associated with better sleep, Dr. Brellenthin said. Another hypothesis is that it causes direct microscopic damage to muscle tissue, forcing that tissue to adapt and grow over time. “So potentially that microscopic damage could provide that extra signal boost to the brain to replenish and repair, and get this person sleep.”

The study was limited by the use of self-reported sleep outcomes and a lack of detailed information on sleep medications, although 81% of participants reported taking no such medications.

The research was supported by a National Institutes of Health/National Heart, Lung, and Blood Institute grant to Dr. Lee. Dr. Brellenthin reports no relevant financial relationships.
 

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

CHICAGO – A randomized trial suggests resistance exercise promotes better sleep than other workouts among inactive adults, particularly those who are poor sleepers.

“We thought resistance exercise would be somewhere in the same neighborhood as aerobic exercise or that maybe combined exercise would be a little bit better but, no, it was consistently resistance exercise, on its own, that seemed to show the most benefits across the board,” Angelique Brellenthin, PhD, told this news organization.

The results were presented at the recent Epidemiology, Prevention/Lifestyle & Cardiometabolic Health meeting sponsored by the American Heart Association.

Even before the pandemic and bedtime “doom scrolling” took hold, research showed that a third of Americans regularly get less than 7 hours of sleep. The AHA recommends aerobic exercise to improve sleep and promote cardiovascular health, yet little is known on how it compares with other types of exercise in the general population, she said.

Dr. Brellenthin and coinvestigator Duck-chul Lee, PhD, both of Iowa State University in Ames, recruited 406 inactive adults, aged 35-70 years, who had obesity or overweight (mean body mass index, 31.2 kg/m²) and had elevated or stage 1 hypertension and randomly assigned them to no exercise or 60 minutes of supervised aerobic, resistance, or combination exercise three times per week for 12 months.

The aerobic exercise group could choose among treadmills, upright or recumbent bikes, and ellipticals, and the participants had their heart rate monitored to ensure they were continuously getting moderate- to vigorous-intensity exercise.

The resistance exercise group performed three sets of 8-16 repetitions at 50%-80% of their one-rep maximum on 12 resistance machines: a leg press, chest press, lat pulldown, leg curl, leg extension, biceps curl, triceps pushdown, shoulder press, abdominal crunch, lower back extension, torso rotation, and hip abduction.

The combination group did 30 minutes of aerobic exercise at moderate to vigorous intensity, and then two sets of 8-16 repetitions of resistance exercise on 9 machines instead of 12.

Exercise adherence over the year was 84%, 77%, and 85%, respectively.

Participants also completed the Pittsburgh Sleep Quality Index (PSQI) at baseline and 12 months. Among the 386 participants (53% women) with evaluable data, 35% had poor-quality sleep, as indicated by a global PSQI score of more than 5, and 42% regularly slept less than 7 hours per night.

In adjusted analyses, sleep duration at 12 months, on average, increased by 13 minutes in the resistance-exercise group (P = .009), decreased by 0.6 minute in the aerobic-exercise group, and increased by 2 minutes in the combined-exercise group and by 4 minutes in the control group.

Among participants who got less than 7 hours of sleep at baseline, however, sleep duration increased by 40 minutes (P < .0001), compared with increases of 23 minutes in the aerobic group, 17 minutes in the combined group, and 15 minutes in the control group.

Overall sleep efficiency, or the ratio of total sleep time to time in bed, improved in the resistance (P = .0005) and combined (P = .03) exercise groups, but not in the aerobic or control groups.

Sleep latency, or the time needed to fall asleep, decreased by 3 minutes in the resistance-exercise group, with no notable changes in the other groups.

Sleep quality and the number of sleep disturbances improved in all groups, including the control group. This could be due to simply being part of a health intervention, which included a month of lifestyle education classes, Dr. Brellenthin suggested.

It’s unclear why the aerobic-exercise group didn’t show greater gains, given the wealth of research showing it improves sleep, she said, but it had fewer poor sleepers at baseline than the resistance group (33% vs. 42%). “So it may be that people who were already getting good sleep didn’t have much room to improve.”

Among the poor-quality sleepers at baseline, resistance exercise significantly improved sleep quality (-2.4 vs. -1.0 points; P = .009) and duration (+36 vs. +3 minutes; P = .02), compared with the control group. It also improved sleep efficiency by 9.0%, compared with 0.9% in the control group (P = .002) and 8.0% for the combined-exercise group (P = .01).

“For a lot of people who know their sleep could be a bit better, this could be a place to start without resorting to medications, if they wanted to focus on a lifestyle intervention,” Dr. Brellenthin said.

It’s not fully understood how resistance exercise improves sleep, but it might contribute to better overall mental health and it might enhance the synthesis and release of certain hormones, such as testosterone and human growth hormone, which are associated with better sleep, Dr. Brellenthin said. Another hypothesis is that it causes direct microscopic damage to muscle tissue, forcing that tissue to adapt and grow over time. “So potentially that microscopic damage could provide that extra signal boost to the brain to replenish and repair, and get this person sleep.”

The study was limited by the use of self-reported sleep outcomes and a lack of detailed information on sleep medications, although 81% of participants reported taking no such medications.

The research was supported by a National Institutes of Health/National Heart, Lung, and Blood Institute grant to Dr. Lee. Dr. Brellenthin reports no relevant financial relationships.
 

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

CHICAGO – A randomized trial suggests resistance exercise promotes better sleep than other workouts among inactive adults, particularly those who are poor sleepers.

“We thought resistance exercise would be somewhere in the same neighborhood as aerobic exercise or that maybe combined exercise would be a little bit better but, no, it was consistently resistance exercise, on its own, that seemed to show the most benefits across the board,” Angelique Brellenthin, PhD, told this news organization.

The results were presented at the recent Epidemiology, Prevention/Lifestyle & Cardiometabolic Health meeting sponsored by the American Heart Association.

Even before the pandemic and bedtime “doom scrolling” took hold, research showed that a third of Americans regularly get less than 7 hours of sleep. The AHA recommends aerobic exercise to improve sleep and promote cardiovascular health, yet little is known on how it compares with other types of exercise in the general population, she said.

Dr. Brellenthin and coinvestigator Duck-chul Lee, PhD, both of Iowa State University in Ames, recruited 406 inactive adults, aged 35-70 years, who had obesity or overweight (mean body mass index, 31.2 kg/m²) and had elevated or stage 1 hypertension and randomly assigned them to no exercise or 60 minutes of supervised aerobic, resistance, or combination exercise three times per week for 12 months.

The aerobic exercise group could choose among treadmills, upright or recumbent bikes, and ellipticals, and the participants had their heart rate monitored to ensure they were continuously getting moderate- to vigorous-intensity exercise.

The resistance exercise group performed three sets of 8-16 repetitions at 50%-80% of their one-rep maximum on 12 resistance machines: a leg press, chest press, lat pulldown, leg curl, leg extension, biceps curl, triceps pushdown, shoulder press, abdominal crunch, lower back extension, torso rotation, and hip abduction.

The combination group did 30 minutes of aerobic exercise at moderate to vigorous intensity, and then two sets of 8-16 repetitions of resistance exercise on 9 machines instead of 12.

Exercise adherence over the year was 84%, 77%, and 85%, respectively.

Participants also completed the Pittsburgh Sleep Quality Index (PSQI) at baseline and 12 months. Among the 386 participants (53% women) with evaluable data, 35% had poor-quality sleep, as indicated by a global PSQI score of more than 5, and 42% regularly slept less than 7 hours per night.

In adjusted analyses, sleep duration at 12 months, on average, increased by 13 minutes in the resistance-exercise group (P = .009), decreased by 0.6 minute in the aerobic-exercise group, and increased by 2 minutes in the combined-exercise group and by 4 minutes in the control group.

Among participants who got less than 7 hours of sleep at baseline, however, sleep duration increased by 40 minutes (P < .0001), compared with increases of 23 minutes in the aerobic group, 17 minutes in the combined group, and 15 minutes in the control group.

Overall sleep efficiency, or the ratio of total sleep time to time in bed, improved in the resistance (P = .0005) and combined (P = .03) exercise groups, but not in the aerobic or control groups.

Sleep latency, or the time needed to fall asleep, decreased by 3 minutes in the resistance-exercise group, with no notable changes in the other groups.

Sleep quality and the number of sleep disturbances improved in all groups, including the control group. This could be due to simply being part of a health intervention, which included a month of lifestyle education classes, Dr. Brellenthin suggested.

It’s unclear why the aerobic-exercise group didn’t show greater gains, given the wealth of research showing it improves sleep, she said, but it had fewer poor sleepers at baseline than the resistance group (33% vs. 42%). “So it may be that people who were already getting good sleep didn’t have much room to improve.”

Among the poor-quality sleepers at baseline, resistance exercise significantly improved sleep quality (-2.4 vs. -1.0 points; P = .009) and duration (+36 vs. +3 minutes; P = .02), compared with the control group. It also improved sleep efficiency by 9.0%, compared with 0.9% in the control group (P = .002) and 8.0% for the combined-exercise group (P = .01).

“For a lot of people who know their sleep could be a bit better, this could be a place to start without resorting to medications, if they wanted to focus on a lifestyle intervention,” Dr. Brellenthin said.

It’s not fully understood how resistance exercise improves sleep, but it might contribute to better overall mental health and it might enhance the synthesis and release of certain hormones, such as testosterone and human growth hormone, which are associated with better sleep, Dr. Brellenthin said. Another hypothesis is that it causes direct microscopic damage to muscle tissue, forcing that tissue to adapt and grow over time. “So potentially that microscopic damage could provide that extra signal boost to the brain to replenish and repair, and get this person sleep.”

The study was limited by the use of self-reported sleep outcomes and a lack of detailed information on sleep medications, although 81% of participants reported taking no such medications.

The research was supported by a National Institutes of Health/National Heart, Lung, and Blood Institute grant to Dr. Lee. Dr. Brellenthin reports no relevant financial relationships.
 

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

The chance that patients with severe aortic stenosis (AS) will receive aortic valve replacement (AVR) is worse than the flip of a coin, even a decade after the gamechanging transcatheter option became available, a new study suggests.

Of the study’s 6,150 patients with an indication or potential indication for AVR, 48% received the procedure at Massachusetts General Hospital and its partner institution Brigham and Women’s Hospital, both in Boston – both of which have active, high-volume transcatheter and surgical AVR (TAVR/SAVR) programs.

“Essentially, this is a best-case scenario. So, unfortunately, I think on the national level we are likely to see rates that are far worse than what we observed here,” senior author Sammy Elmariah, MD, PhD, Massachusetts General Hospital, told this news organization.

The volume of AVR increased more than 10-fold over the 18-year study period (2000 to 2017), driven by the exponential growth of TAVR, he noted. However, the graying of America led to an even greater increase in the number of patients with severe AS and an indication for AVR.

The study, led by Shawn X. Li, MD, MBA, of Mass General, was published in the March 8 issue of the Journal of the American College of Cardiology.

Previous research has provided equally compelling data on the undertreatment of AS, including a 2021 study using natural language processing (NLP) that found AVR use was just 35.6% within 1 year of diagnosis and varied wildly among managing cardiologists.

The present study used NLP tools to identify symptoms consistent with severe AS in the medical record coupled with echocardiographic data from 10,795 patients with severe AS (valve area <1 cm2). Patients were divided into four AS subtypes and then classified as having a class 1 indication (high-gradient AS with symptoms or reduced ejection fraction [EF]) or a potential class 2a indication (low-gradient AS with symptoms) for AVR.

Among patients with high-gradient AS and class 1 indication for AVR, 1 in 3 did not receive AVR over the study period, including 30% with a normal EF and 47% with a low EF.

In those with low-gradient AS, 67% with a normal EF and 62% with a low EF did not receive AVR. The low-gradient groups were significantly less likely to receive AVR both in the entire study period and in the more contemporary period from 2014 to 2017, despite the valvular heart disease guideline 2014 update indicating AVR was “reasonable” in patients with low-gradient AS – a 2a recommendation upgraded to class 1 in the most recent 2020 update.
 

Better survival

In patients with a class 1 or potential class 2a indication, AVR was associated with a significantly lower risk of mortality in all four AS subgroups:

• High gradient/normal EF: 3% vs. 15%; adjusted hazard ratio, 0.42
• High-gradient/low EF: 16% vs. 72%; aHR, 0.28
• Low-gradient/normal EF: 5% vs. 14%; aHR, 0.73
• Low-gradient/low EF: 11% vs. 34%; aHR, 0.48; P < .001 for all

“I think what we need to do is change the paradigm, such that patients with a valve area that is less than or equal to 1 [cm2] is severe aortic stenosis until proven otherwise, and that essentially establishes a premise by which we default to treat these patients unless we can prove that it is in fact moderate,” Dr. Elmariah said.

Unfortunately, the opposite is currently true today, he said, and the default is not to treat and put patients through surgery or an invasive TAVR procedure unless physicians can definitively prove that it is severe AS. But they’re not always correct and don’t always have the ability to truly differentiate moderate from severe disease.

“The question, therefore, is ‘What do we do with those patients?’” Dr. Elmariah asked. “I think if a patient has symptoms, then we are obligated to intervene, given the stark difference in mortality that one sees when these patients go undertreated.”
 

Sounding the alarm

Robert Bonow, MD, a professor of cardiology at Northwestern University in Chicago and a writing committee member for the 2014 guideline update, said the study is a “big wake-up call” and “the take-home message is that we are missing some patients who have treatable aortic stenosis.”

The sheer magnitude of the problem, however, can be difficult to fully ascertain from administrative data like this, he said. Notably, patients who did not receive AVR were significantly older, with 37% aged 81-90 years and 12% over age 90, and had a lower hematocrit and lower estimated glomerular filtration rate. But it’s not clear how many had cancer, end-stage renal disease, or severe lung disease, which could have factored into the decision to undergo AVR.

“What’s also an issue is that over 50% of patients had low gradient disease, which is very problematic and takes careful assessment in an individual patient,” said Dr. Bonow, who is also editor-in-chief of JAMA Cardiology. “That’s all being generated by a low valve area of less than 1 cm2 from echo reports, so that’s not necessarily a careful prospective echo assessment ... so some of the patients with low-gradient disease may not have true severe aortic stenosis.”

Dr. Elmariah agreed that echocardiogram reports are not always clear cut and pointed out that referral to a valve specialist was highly predictive of whether or not a patient underwent AVR, supporting the class 1 guideline recommendation.

He also noted that Mass General is launching the DETECT-AS trial to determine whether electronic physician notifications highlighting clinical practice guideline recommendations will improve AVR utilization over standard care in 940 patients with severe AS on echocardiogram, defined by a valve area less than 1 cm2.

Reached for comment, Catherine Otto, MD, director of the Heart Valve Clinic at the University of Washington, Seattle, and a fellow member of the 2014 guideline writing committee, said “this adds to the data [that] we’re undertreating severe aortic stenosis, and it continues to be surprising given the availability of transcatheter options.”

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

The chance that patients with severe aortic stenosis (AS) will receive aortic valve replacement (AVR) is worse than the flip of a coin, even a decade after the gamechanging transcatheter option became available, a new study suggests.

Of the study’s 6,150 patients with an indication or potential indication for AVR, 48% received the procedure at Massachusetts General Hospital and its partner institution Brigham and Women’s Hospital, both in Boston – both of which have active, high-volume transcatheter and surgical AVR (TAVR/SAVR) programs.

“Essentially, this is a best-case scenario. So, unfortunately, I think on the national level we are likely to see rates that are far worse than what we observed here,” senior author Sammy Elmariah, MD, PhD, Massachusetts General Hospital, told this news organization.

The volume of AVR increased more than 10-fold over the 18-year study period (2000 to 2017), driven by the exponential growth of TAVR, he noted. However, the graying of America led to an even greater increase in the number of patients with severe AS and an indication for AVR.

The study, led by Shawn X. Li, MD, MBA, of Mass General, was published in the March 8 issue of the Journal of the American College of Cardiology.

Previous research has provided equally compelling data on the undertreatment of AS, including a 2021 study using natural language processing (NLP) that found AVR use was just 35.6% within 1 year of diagnosis and varied wildly among managing cardiologists.

The present study used NLP tools to identify symptoms consistent with severe AS in the medical record coupled with echocardiographic data from 10,795 patients with severe AS (valve area <1 cm2). Patients were divided into four AS subtypes and then classified as having a class 1 indication (high-gradient AS with symptoms or reduced ejection fraction [EF]) or a potential class 2a indication (low-gradient AS with symptoms) for AVR.

Among patients with high-gradient AS and class 1 indication for AVR, 1 in 3 did not receive AVR over the study period, including 30% with a normal EF and 47% with a low EF.

In those with low-gradient AS, 67% with a normal EF and 62% with a low EF did not receive AVR. The low-gradient groups were significantly less likely to receive AVR both in the entire study period and in the more contemporary period from 2014 to 2017, despite the valvular heart disease guideline 2014 update indicating AVR was “reasonable” in patients with low-gradient AS – a 2a recommendation upgraded to class 1 in the most recent 2020 update.
 

Better survival

In patients with a class 1 or potential class 2a indication, AVR was associated with a significantly lower risk of mortality in all four AS subgroups:

• High gradient/normal EF: 3% vs. 15%; adjusted hazard ratio, 0.42
• High-gradient/low EF: 16% vs. 72%; aHR, 0.28
• Low-gradient/normal EF: 5% vs. 14%; aHR, 0.73
• Low-gradient/low EF: 11% vs. 34%; aHR, 0.48; P < .001 for all

“I think what we need to do is change the paradigm, such that patients with a valve area that is less than or equal to 1 [cm2] is severe aortic stenosis until proven otherwise, and that essentially establishes a premise by which we default to treat these patients unless we can prove that it is in fact moderate,” Dr. Elmariah said.

Unfortunately, the opposite is currently true today, he said, and the default is not to treat and put patients through surgery or an invasive TAVR procedure unless physicians can definitively prove that it is severe AS. But they’re not always correct and don’t always have the ability to truly differentiate moderate from severe disease.

“The question, therefore, is ‘What do we do with those patients?’” Dr. Elmariah asked. “I think if a patient has symptoms, then we are obligated to intervene, given the stark difference in mortality that one sees when these patients go undertreated.”
 

Sounding the alarm

Robert Bonow, MD, a professor of cardiology at Northwestern University in Chicago and a writing committee member for the 2014 guideline update, said the study is a “big wake-up call” and “the take-home message is that we are missing some patients who have treatable aortic stenosis.”

The sheer magnitude of the problem, however, can be difficult to fully ascertain from administrative data like this, he said. Notably, patients who did not receive AVR were significantly older, with 37% aged 81-90 years and 12% over age 90, and had a lower hematocrit and lower estimated glomerular filtration rate. But it’s not clear how many had cancer, end-stage renal disease, or severe lung disease, which could have factored into the decision to undergo AVR.

“What’s also an issue is that over 50% of patients had low gradient disease, which is very problematic and takes careful assessment in an individual patient,” said Dr. Bonow, who is also editor-in-chief of JAMA Cardiology. “That’s all being generated by a low valve area of less than 1 cm2 from echo reports, so that’s not necessarily a careful prospective echo assessment ... so some of the patients with low-gradient disease may not have true severe aortic stenosis.”

Dr. Elmariah agreed that echocardiogram reports are not always clear cut and pointed out that referral to a valve specialist was highly predictive of whether or not a patient underwent AVR, supporting the class 1 guideline recommendation.

He also noted that Mass General is launching the DETECT-AS trial to determine whether electronic physician notifications highlighting clinical practice guideline recommendations will improve AVR utilization over standard care in 940 patients with severe AS on echocardiogram, defined by a valve area less than 1 cm2.

Reached for comment, Catherine Otto, MD, director of the Heart Valve Clinic at the University of Washington, Seattle, and a fellow member of the 2014 guideline writing committee, said “this adds to the data [that] we’re undertreating severe aortic stenosis, and it continues to be surprising given the availability of transcatheter options.”

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

The chance that patients with severe aortic stenosis (AS) will receive aortic valve replacement (AVR) is worse than the flip of a coin, even a decade after the gamechanging transcatheter option became available, a new study suggests.

Of the study’s 6,150 patients with an indication or potential indication for AVR, 48% received the procedure at Massachusetts General Hospital and its partner institution Brigham and Women’s Hospital, both in Boston – both of which have active, high-volume transcatheter and surgical AVR (TAVR/SAVR) programs.

“Essentially, this is a best-case scenario. So, unfortunately, I think on the national level we are likely to see rates that are far worse than what we observed here,” senior author Sammy Elmariah, MD, PhD, Massachusetts General Hospital, told this news organization.

The volume of AVR increased more than 10-fold over the 18-year study period (2000 to 2017), driven by the exponential growth of TAVR, he noted. However, the graying of America led to an even greater increase in the number of patients with severe AS and an indication for AVR.

The study, led by Shawn X. Li, MD, MBA, of Mass General, was published in the March 8 issue of the Journal of the American College of Cardiology.

Previous research has provided equally compelling data on the undertreatment of AS, including a 2021 study using natural language processing (NLP) that found AVR use was just 35.6% within 1 year of diagnosis and varied wildly among managing cardiologists.

The present study used NLP tools to identify symptoms consistent with severe AS in the medical record coupled with echocardiographic data from 10,795 patients with severe AS (valve area <1 cm2). Patients were divided into four AS subtypes and then classified as having a class 1 indication (high-gradient AS with symptoms or reduced ejection fraction [EF]) or a potential class 2a indication (low-gradient AS with symptoms) for AVR.

Among patients with high-gradient AS and class 1 indication for AVR, 1 in 3 did not receive AVR over the study period, including 30% with a normal EF and 47% with a low EF.

In those with low-gradient AS, 67% with a normal EF and 62% with a low EF did not receive AVR. The low-gradient groups were significantly less likely to receive AVR both in the entire study period and in the more contemporary period from 2014 to 2017, despite the valvular heart disease guideline 2014 update indicating AVR was “reasonable” in patients with low-gradient AS – a 2a recommendation upgraded to class 1 in the most recent 2020 update.
 

Better survival

In patients with a class 1 or potential class 2a indication, AVR was associated with a significantly lower risk of mortality in all four AS subgroups:

• High gradient/normal EF: 3% vs. 15%; adjusted hazard ratio, 0.42
• High-gradient/low EF: 16% vs. 72%; aHR, 0.28
• Low-gradient/normal EF: 5% vs. 14%; aHR, 0.73
• Low-gradient/low EF: 11% vs. 34%; aHR, 0.48; P < .001 for all

“I think what we need to do is change the paradigm, such that patients with a valve area that is less than or equal to 1 [cm2] is severe aortic stenosis until proven otherwise, and that essentially establishes a premise by which we default to treat these patients unless we can prove that it is in fact moderate,” Dr. Elmariah said.

Unfortunately, the opposite is currently true today, he said, and the default is not to treat and put patients through surgery or an invasive TAVR procedure unless physicians can definitively prove that it is severe AS. But they’re not always correct and don’t always have the ability to truly differentiate moderate from severe disease.

“The question, therefore, is ‘What do we do with those patients?’” Dr. Elmariah asked. “I think if a patient has symptoms, then we are obligated to intervene, given the stark difference in mortality that one sees when these patients go undertreated.”
 

Sounding the alarm

Robert Bonow, MD, a professor of cardiology at Northwestern University in Chicago and a writing committee member for the 2014 guideline update, said the study is a “big wake-up call” and “the take-home message is that we are missing some patients who have treatable aortic stenosis.”

The sheer magnitude of the problem, however, can be difficult to fully ascertain from administrative data like this, he said. Notably, patients who did not receive AVR were significantly older, with 37% aged 81-90 years and 12% over age 90, and had a lower hematocrit and lower estimated glomerular filtration rate. But it’s not clear how many had cancer, end-stage renal disease, or severe lung disease, which could have factored into the decision to undergo AVR.

“What’s also an issue is that over 50% of patients had low gradient disease, which is very problematic and takes careful assessment in an individual patient,” said Dr. Bonow, who is also editor-in-chief of JAMA Cardiology. “That’s all being generated by a low valve area of less than 1 cm2 from echo reports, so that’s not necessarily a careful prospective echo assessment ... so some of the patients with low-gradient disease may not have true severe aortic stenosis.”

Dr. Elmariah agreed that echocardiogram reports are not always clear cut and pointed out that referral to a valve specialist was highly predictive of whether or not a patient underwent AVR, supporting the class 1 guideline recommendation.

He also noted that Mass General is launching the DETECT-AS trial to determine whether electronic physician notifications highlighting clinical practice guideline recommendations will improve AVR utilization over standard care in 940 patients with severe AS on echocardiogram, defined by a valve area less than 1 cm2.

Reached for comment, Catherine Otto, MD, director of the Heart Valve Clinic at the University of Washington, Seattle, and a fellow member of the 2014 guideline writing committee, said “this adds to the data [that] we’re undertreating severe aortic stenosis, and it continues to be surprising given the availability of transcatheter options.”

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

Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).

The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.

However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.

The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).

“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”

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

Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).

The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.

However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.

The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).

“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”

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

Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).

The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.

However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.

The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).

“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”

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

Catholic Medical Center has agreed to pay $3.8 million to settle claims it provided free call coverage to a cardiologist in exchange for patient referrals to the Manchester, N.H., hospital, according to federal officials.

“The cardiologist who received the free call coverage referred millions of dollars in medical procedures and services to CMC over the decade in which the free services were provided,” the Department of Justice said in a news release.

Because the hospital submitted claims for payment to Medicare, Medicaid, and other federal health care programs for the services referred by the cardiologist, the government alleged the claims were the result of unlawful kickbacks.

The settlement resolves allegations brought in a whistleblower lawsuit filed in 2018 by cardiologist David Goldberg, MD, who previously worked at Catholic Medical Center (CMC) and is represented by Douglas, Leonard & Garvey.

The news release did not name the cardiologist involved in the alleged kickback scheme but the recently unsealed lawsuit says CMC paid its cardiologists above market rates ($10,000 per weekend, $3,000 per night) to provide free coverage services for Mary-Claire Paicopolis, MD.

The lawsuit also claims Dr. Paicopolis insisted the hospital implant only Boston Scientific devices in her patients and that her preferred electrophysiologist use only its Rhythmia mapping system during ablation procedures. To keep CMC from objecting, the suit alleges Boston Scientific offered CMC early access to its Watchman left atrial appendage occluder and provided “unprecedented” support to a nonacademic community hospital site.

“It went back several years, and that and the other issues in the suit were strong motivators for Dr. Goldberg to try to rectify the situation and he deserves a lot of credit for having done so,” attorney Charles G. Douglas III told this news organization.

Dr. Goldberg will receive $570,000 of the $3.8 million settlement as well as $145,361 in expenses, attorney fees, and costs.

Although not addressed in the federal news release, the lawsuit also alleges that CMC staff manipulated mortality data by discharging patients from the ICU and then readmitting them to hospice with a new patient number, “thereby avoiding the need to claim a surgical mortality.”

The lawsuit also says CMC “created a practice of covering up medical errors” and detailed 12 patient deaths between 2012 and 2018, alleging that these deaths were the result of substandard care.

CMC spokesperson Lauren Collins-Cline said in an email that the call coverage arrangement is no longer in place and originated almost 15 years ago with the input of legal counsel in order to provide high-quality care for patients.

“While CMC vigorously disagrees with the government’s allegations that this arrangement violated federal law, we have agreed to settle in order to avoid long costly civil litigation,” she said.

As to the other claims in the complaint, Ms. Collins-Cline said they were investigated by the government and dismissed per the settlement agreement. “CMC holds itself to the highest ethical standards in patient care and business conduct. That’s embedded in our mission and will always remain our highest priority.”

Mr. Douglas, however, said the government retains the right to pursue other claims in the lawsuit in the future. “So, [the hospital] is a little more optimistic than the reality of what the government agrees is the situation.”

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

Catholic Medical Center has agreed to pay $3.8 million to settle claims it provided free call coverage to a cardiologist in exchange for patient referrals to the Manchester, N.H., hospital, according to federal officials.

“The cardiologist who received the free call coverage referred millions of dollars in medical procedures and services to CMC over the decade in which the free services were provided,” the Department of Justice said in a news release.

Because the hospital submitted claims for payment to Medicare, Medicaid, and other federal health care programs for the services referred by the cardiologist, the government alleged the claims were the result of unlawful kickbacks.

The settlement resolves allegations brought in a whistleblower lawsuit filed in 2018 by cardiologist David Goldberg, MD, who previously worked at Catholic Medical Center (CMC) and is represented by Douglas, Leonard & Garvey.

The news release did not name the cardiologist involved in the alleged kickback scheme but the recently unsealed lawsuit says CMC paid its cardiologists above market rates ($10,000 per weekend, $3,000 per night) to provide free coverage services for Mary-Claire Paicopolis, MD.

The lawsuit also claims Dr. Paicopolis insisted the hospital implant only Boston Scientific devices in her patients and that her preferred electrophysiologist use only its Rhythmia mapping system during ablation procedures. To keep CMC from objecting, the suit alleges Boston Scientific offered CMC early access to its Watchman left atrial appendage occluder and provided “unprecedented” support to a nonacademic community hospital site.

“It went back several years, and that and the other issues in the suit were strong motivators for Dr. Goldberg to try to rectify the situation and he deserves a lot of credit for having done so,” attorney Charles G. Douglas III told this news organization.

Dr. Goldberg will receive $570,000 of the $3.8 million settlement as well as $145,361 in expenses, attorney fees, and costs.

Although not addressed in the federal news release, the lawsuit also alleges that CMC staff manipulated mortality data by discharging patients from the ICU and then readmitting them to hospice with a new patient number, “thereby avoiding the need to claim a surgical mortality.”

The lawsuit also says CMC “created a practice of covering up medical errors” and detailed 12 patient deaths between 2012 and 2018, alleging that these deaths were the result of substandard care.

CMC spokesperson Lauren Collins-Cline said in an email that the call coverage arrangement is no longer in place and originated almost 15 years ago with the input of legal counsel in order to provide high-quality care for patients.

“While CMC vigorously disagrees with the government’s allegations that this arrangement violated federal law, we have agreed to settle in order to avoid long costly civil litigation,” she said.

As to the other claims in the complaint, Ms. Collins-Cline said they were investigated by the government and dismissed per the settlement agreement. “CMC holds itself to the highest ethical standards in patient care and business conduct. That’s embedded in our mission and will always remain our highest priority.”

Mr. Douglas, however, said the government retains the right to pursue other claims in the lawsuit in the future. “So, [the hospital] is a little more optimistic than the reality of what the government agrees is the situation.”

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

Catholic Medical Center has agreed to pay $3.8 million to settle claims it provided free call coverage to a cardiologist in exchange for patient referrals to the Manchester, N.H., hospital, according to federal officials.

“The cardiologist who received the free call coverage referred millions of dollars in medical procedures and services to CMC over the decade in which the free services were provided,” the Department of Justice said in a news release.

Because the hospital submitted claims for payment to Medicare, Medicaid, and other federal health care programs for the services referred by the cardiologist, the government alleged the claims were the result of unlawful kickbacks.

The settlement resolves allegations brought in a whistleblower lawsuit filed in 2018 by cardiologist David Goldberg, MD, who previously worked at Catholic Medical Center (CMC) and is represented by Douglas, Leonard & Garvey.

The news release did not name the cardiologist involved in the alleged kickback scheme but the recently unsealed lawsuit says CMC paid its cardiologists above market rates ($10,000 per weekend, $3,000 per night) to provide free coverage services for Mary-Claire Paicopolis, MD.

The lawsuit also claims Dr. Paicopolis insisted the hospital implant only Boston Scientific devices in her patients and that her preferred electrophysiologist use only its Rhythmia mapping system during ablation procedures. To keep CMC from objecting, the suit alleges Boston Scientific offered CMC early access to its Watchman left atrial appendage occluder and provided “unprecedented” support to a nonacademic community hospital site.

“It went back several years, and that and the other issues in the suit were strong motivators for Dr. Goldberg to try to rectify the situation and he deserves a lot of credit for having done so,” attorney Charles G. Douglas III told this news organization.

Dr. Goldberg will receive $570,000 of the $3.8 million settlement as well as $145,361 in expenses, attorney fees, and costs.

Although not addressed in the federal news release, the lawsuit also alleges that CMC staff manipulated mortality data by discharging patients from the ICU and then readmitting them to hospice with a new patient number, “thereby avoiding the need to claim a surgical mortality.”

The lawsuit also says CMC “created a practice of covering up medical errors” and detailed 12 patient deaths between 2012 and 2018, alleging that these deaths were the result of substandard care.

CMC spokesperson Lauren Collins-Cline said in an email that the call coverage arrangement is no longer in place and originated almost 15 years ago with the input of legal counsel in order to provide high-quality care for patients.

“While CMC vigorously disagrees with the government’s allegations that this arrangement violated federal law, we have agreed to settle in order to avoid long costly civil litigation,” she said.

As to the other claims in the complaint, Ms. Collins-Cline said they were investigated by the government and dismissed per the settlement agreement. “CMC holds itself to the highest ethical standards in patient care and business conduct. That’s embedded in our mission and will always remain our highest priority.”

Mr. Douglas, however, said the government retains the right to pursue other claims in the lawsuit in the future. “So, [the hospital] is a little more optimistic than the reality of what the government agrees is the situation.”

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

Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.

Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).

The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.

The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).

Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).

“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.

But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.

“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.

“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.

Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).

“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”

The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.

“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”

Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.

The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”

Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.

“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”

In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”

A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.

Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”

Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.

They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.

“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”

Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.

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

Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.

Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).

The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.

The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).

Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).

“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.

But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.

“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.

“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.

Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).

“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”

The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.

“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”

Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.

The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”

Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.

“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”

In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”

A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.

Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”

Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.

They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.

“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”

Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.

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

Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.

Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).

The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.

The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).

Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).

“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.

But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.

“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.

“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.

Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).

“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”

The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.

“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”

Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.

The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”

Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.

“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”

In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”

A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.

Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”

Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.

They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.

“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”

Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.

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

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

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

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

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

Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.

Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.

High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.

SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.

The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.

No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.

Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.

Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.

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

Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.

A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.

Bruce Jancin/MDedge News

Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).

“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.

The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”

The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”

All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.

Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.

The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.

The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
 

Guidelines upside down?

In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.

“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.

In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.

“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.

“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”

In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
 

Not all strategies are ‘created equal’

The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).

Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.

He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.

The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.

“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”

Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.

“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”

As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”

Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.

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

Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.

A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.

Bruce Jancin/MDedge News

Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).

“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.

The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”

The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”

All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.

Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.

The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.

The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
 

Guidelines upside down?

In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.

“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.

In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.

“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.

“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”

In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
 

Not all strategies are ‘created equal’

The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).

Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.

He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.

The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.

“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”

Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.

“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”

As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”

Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.

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

Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.

A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.

Bruce Jancin/MDedge News

Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).

“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.

The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”

The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”

All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.

Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.

The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.

The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
 

Guidelines upside down?

In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.

“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.

In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.

“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.

“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”

In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
 

Not all strategies are ‘created equal’

The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).

Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.

He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.

The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.

“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”

Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.

“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”

As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”

Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.

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

People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.

“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”

Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”

Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.

“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”

For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.

As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.

“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.

Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:

• Stroke: HR, 1.52; burden, 4.03
• Transient ischemic attack: HR, 1.49; burden, 1.84
• Dysrhythmias: HR, 1.69; burden, 19.86
• Ischemic heart disease: HR, 1.66; burden, 7.28
• Heart failure: HR, 1.72; burden, 11.61
• Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
• Pulmonary embolism: HR, 2.93; burden, 5.47
• Deep vein thrombosis: HR, 2.09; burden, 4.18
• Pericarditis: HR, 1.85, burden, 0.98
• Myocarditis: HR, 5.38; burden, 0.31

Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.

The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.

The overall results were also consistent when compared with the historical control subjects.

“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”

With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”

Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”

The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.

The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.

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

People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.

“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”

Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”

Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.

“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”

For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.

As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.

“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.

Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:

• Stroke: HR, 1.52; burden, 4.03
• Transient ischemic attack: HR, 1.49; burden, 1.84
• Dysrhythmias: HR, 1.69; burden, 19.86
• Ischemic heart disease: HR, 1.66; burden, 7.28
• Heart failure: HR, 1.72; burden, 11.61
• Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
• Pulmonary embolism: HR, 2.93; burden, 5.47
• Deep vein thrombosis: HR, 2.09; burden, 4.18
• Pericarditis: HR, 1.85, burden, 0.98
• Myocarditis: HR, 5.38; burden, 0.31

Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.

The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.

The overall results were also consistent when compared with the historical control subjects.

“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”

With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”

Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”

The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.

The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.

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

People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.

“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”

Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”

Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.

“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”

For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.

As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.

“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.

Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:

• Stroke: HR, 1.52; burden, 4.03
• Transient ischemic attack: HR, 1.49; burden, 1.84
• Dysrhythmias: HR, 1.69; burden, 19.86
• Ischemic heart disease: HR, 1.66; burden, 7.28
• Heart failure: HR, 1.72; burden, 11.61
• Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
• Pulmonary embolism: HR, 2.93; burden, 5.47
• Deep vein thrombosis: HR, 2.09; burden, 4.18
• Pericarditis: HR, 1.85, burden, 0.98
• Myocarditis: HR, 5.38; burden, 0.31

Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.

The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.

The overall results were also consistent when compared with the historical control subjects.

“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”

With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”

Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”

The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.

The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.

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

A new study offers early validation of the recently released Valve Academic Research Consortium 3 (VARC-3) definition of technical success after transcatheter aortic valve replacement (TAVR) and highlights its role in patient prognosis.

Results show that one in 10 patients (11.6%) undergoing TAVR with contemporary devices and techniques experiences technical failure, according to VARC-3.

At 30 days, patients with technical failure had significantly higher rates of the composite of cardiovascular (CV) death or stroke (11.5% vs. 3.5%), CV death (6.0% vs. 1.0%), and stroke (7.2% vs. 2.9%), compared with those with technical success.

Technical failure after TAVR was also independently associated with a twofold higher risk for CV death or stroke at 1 year (20.0% vs. 10.3%; hazard ratio, 2.01; 95% CI, 1.37-2.95).

Other independent predictors were history of peripheral artery disease (HR, 1.97), New York Heart Association III or IV disease (HR, 1.86), baseline moderate or greater mitral regurgitation (HR, 1.48), atrial fibrillation (HR, 1.40), and Society of Thoracic Surgeons predicted mortality risk (HR, 1.04).

“We were expecting that we were getting better over time with device iterations, with more experience, so we weren’t surprised by the result. But I think what is somewhat surprising is how much of an impact it has on the outcome,” senior study author Thomas Pilgrim, MD, Inselspital, University of Bern, Switzerland, told this news organization.

The VARC-3 document, introduced last year to some controversy, features a heavier focus on patient outcomes, as well as composite safety and efficacy endpoints. The definition of technical success after TAVR includes freedom from death; successful access, delivery of the device, and retrieval of the delivery system; correct positioning of a prosthetic heart valve into the proper anatomical location; and freedom from surgery or intervention related to the device or to an access-related or cardiac structural complication.

The composite endpoint is meant to replace the VARC-2 definition of “device success,” which also included freedom from death and correct valve positioning but required echocardiographic evaluation. With VARC-3, there is an “immediate measure” of success without having to wait for echocardiography, observed Dr. Pilgrim.

As reported in the Journal of the American College of Cardiology Cardiovascular Interventions, TAVR was a technical success in 1,435 of 1,624 (88.4%) patients. Technical failure occurred in 189 patients related to either vascular complications (8.6%) or procedural death or cardiac complications (3.0%).

The VARC-2 endpoint of device success was observed in 66.1% of patients. The high rate of device failure was largely attributed to a 28% incidence of prosthesis-patient mismatch.

“If you use the VARC-2 device success [definition], you include this patient–prosthesis mismatch, the [valve] gradients, [and] regurgitation and then device success is always lower,” Dr. Pilgrim said.

Asked whether the VARC-3 definition may be missing case failures, he replied: “At this stage, we don’t know how important these echocardiographic parameters are for hard clinical endpoints. Maybe the VARC-2 endpoint was too sensitive or the VARC-3 endpoint is not sensitive enough. This is something we just don’t know at this stage.”

Marco Barbanti, MD, an interventional cardiologist at Rodolico Polyclinic University Hospital-San Marco, Catania, Italy, and author of an accompanying editorial, said VARC-3 represents a more accurate indicator of immediate success of the procedure.

“It’s a more pertinent definition according to what really has an impact on prognosis, and, according to the results of this paper, actually, the calibration of this new definition is quite good,” Dr. Barbanti said in an interview.

Patients with VARC-3 technical failure were older, had a higher body mass index, and had more advanced heart failure symptoms than those with technical success. There were no significant differences between the two groups in echocardiographic or CT data, anesthetic strategy, valve type or size, or use of pre- or post-dilation.

All patients underwent TAVR with current balloon-expandable (Sapien 3/Sapien Ultra, Edwards Lifesciences) or self-expanding (Evolut R/PRO [Medtronic], Portico [Abbott], Symetis ACURATE/ACURATE neo [Boston Scientific]) devices between March 2012 and December 2019. A transfemoral approach was used in 92.5% of patients.

In a landmark analysis with the landmark set at 30 days, the effect of technical failure on adverse outcome was limited to the first 30 days (composite endpoint 0-30 days: HR, 3.42; P < .001; 30-360 days: HR, 1.36; P = .266; P for interaction = .002).

At 1 year, the composite of CV death and stroke endpoint occurred in 24.1% of patients with cardiac technical failure, in 18.8% of patients with vascular technical failure, and in 10.3% of patients with technical success.

In multivariate analyses, cardiac and vascular technical failures were independently associated with a 2.6-fold and 1.9-fold increased risk, respectively, for the composite of cardiovascular death and stroke at 1 year.

Female sex, larger device landing zone calcium volume, and earlier procedures (March 2012 to July 2016) were associated with a higher risk for cardiac technical failure, whereas, consistent with previous studies, higher body mass index and use of the Prostar/Manta versus the ProGlide closure device predicted vascular technical failure.

The findings “underscore that technical success is highly clinically relevant and may serve as one of the pivotal endpoints to evaluate the improvement of TAVR or for head-to-head comparisons of new devices in future clinical trials,” the authors conclude.

The findings reflect the experience of a single high-volume center with highly experienced operators in the prospective BERN TAVR registry, however, and may not be generalizable to other heart centers, they note. Although the registry has standardized follow-up, independent analysis of echocardiographic and CT, and independent event adjudication, vascular anatomy was not systematically assessed, and the potential exists for confounding from unmeasured variables.

Dr. Pilgrim reports research grants to the institution from Edwards Lifesciences, Boston Scientific, and Biotronik, personal fees from Biotronik and Boston Scientific, and other from HighLife SAS. Dr. Barbanti is a consultant for Edwards Lifesciences and Boston Scientific.

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

A new study offers early validation of the recently released Valve Academic Research Consortium 3 (VARC-3) definition of technical success after transcatheter aortic valve replacement (TAVR) and highlights its role in patient prognosis.

Results show that one in 10 patients (11.6%) undergoing TAVR with contemporary devices and techniques experiences technical failure, according to VARC-3.

At 30 days, patients with technical failure had significantly higher rates of the composite of cardiovascular (CV) death or stroke (11.5% vs. 3.5%), CV death (6.0% vs. 1.0%), and stroke (7.2% vs. 2.9%), compared with those with technical success.

Technical failure after TAVR was also independently associated with a twofold higher risk for CV death or stroke at 1 year (20.0% vs. 10.3%; hazard ratio, 2.01; 95% CI, 1.37-2.95).

Other independent predictors were history of peripheral artery disease (HR, 1.97), New York Heart Association III or IV disease (HR, 1.86), baseline moderate or greater mitral regurgitation (HR, 1.48), atrial fibrillation (HR, 1.40), and Society of Thoracic Surgeons predicted mortality risk (HR, 1.04).

“We were expecting that we were getting better over time with device iterations, with more experience, so we weren’t surprised by the result. But I think what is somewhat surprising is how much of an impact it has on the outcome,” senior study author Thomas Pilgrim, MD, Inselspital, University of Bern, Switzerland, told this news organization.

The VARC-3 document, introduced last year to some controversy, features a heavier focus on patient outcomes, as well as composite safety and efficacy endpoints. The definition of technical success after TAVR includes freedom from death; successful access, delivery of the device, and retrieval of the delivery system; correct positioning of a prosthetic heart valve into the proper anatomical location; and freedom from surgery or intervention related to the device or to an access-related or cardiac structural complication.

The composite endpoint is meant to replace the VARC-2 definition of “device success,” which also included freedom from death and correct valve positioning but required echocardiographic evaluation. With VARC-3, there is an “immediate measure” of success without having to wait for echocardiography, observed Dr. Pilgrim.

As reported in the Journal of the American College of Cardiology Cardiovascular Interventions, TAVR was a technical success in 1,435 of 1,624 (88.4%) patients. Technical failure occurred in 189 patients related to either vascular complications (8.6%) or procedural death or cardiac complications (3.0%).

The VARC-2 endpoint of device success was observed in 66.1% of patients. The high rate of device failure was largely attributed to a 28% incidence of prosthesis-patient mismatch.

“If you use the VARC-2 device success [definition], you include this patient–prosthesis mismatch, the [valve] gradients, [and] regurgitation and then device success is always lower,” Dr. Pilgrim said.

Asked whether the VARC-3 definition may be missing case failures, he replied: “At this stage, we don’t know how important these echocardiographic parameters are for hard clinical endpoints. Maybe the VARC-2 endpoint was too sensitive or the VARC-3 endpoint is not sensitive enough. This is something we just don’t know at this stage.”

Marco Barbanti, MD, an interventional cardiologist at Rodolico Polyclinic University Hospital-San Marco, Catania, Italy, and author of an accompanying editorial, said VARC-3 represents a more accurate indicator of immediate success of the procedure.

“It’s a more pertinent definition according to what really has an impact on prognosis, and, according to the results of this paper, actually, the calibration of this new definition is quite good,” Dr. Barbanti said in an interview.

Patients with VARC-3 technical failure were older, had a higher body mass index, and had more advanced heart failure symptoms than those with technical success. There were no significant differences between the two groups in echocardiographic or CT data, anesthetic strategy, valve type or size, or use of pre- or post-dilation.

All patients underwent TAVR with current balloon-expandable (Sapien 3/Sapien Ultra, Edwards Lifesciences) or self-expanding (Evolut R/PRO [Medtronic], Portico [Abbott], Symetis ACURATE/ACURATE neo [Boston Scientific]) devices between March 2012 and December 2019. A transfemoral approach was used in 92.5% of patients.

In a landmark analysis with the landmark set at 30 days, the effect of technical failure on adverse outcome was limited to the first 30 days (composite endpoint 0-30 days: HR, 3.42; P < .001; 30-360 days: HR, 1.36; P = .266; P for interaction = .002).

At 1 year, the composite of CV death and stroke endpoint occurred in 24.1% of patients with cardiac technical failure, in 18.8% of patients with vascular technical failure, and in 10.3% of patients with technical success.

In multivariate analyses, cardiac and vascular technical failures were independently associated with a 2.6-fold and 1.9-fold increased risk, respectively, for the composite of cardiovascular death and stroke at 1 year.

Female sex, larger device landing zone calcium volume, and earlier procedures (March 2012 to July 2016) were associated with a higher risk for cardiac technical failure, whereas, consistent with previous studies, higher body mass index and use of the Prostar/Manta versus the ProGlide closure device predicted vascular technical failure.

The findings “underscore that technical success is highly clinically relevant and may serve as one of the pivotal endpoints to evaluate the improvement of TAVR or for head-to-head comparisons of new devices in future clinical trials,” the authors conclude.

The findings reflect the experience of a single high-volume center with highly experienced operators in the prospective BERN TAVR registry, however, and may not be generalizable to other heart centers, they note. Although the registry has standardized follow-up, independent analysis of echocardiographic and CT, and independent event adjudication, vascular anatomy was not systematically assessed, and the potential exists for confounding from unmeasured variables.

Dr. Pilgrim reports research grants to the institution from Edwards Lifesciences, Boston Scientific, and Biotronik, personal fees from Biotronik and Boston Scientific, and other from HighLife SAS. Dr. Barbanti is a consultant for Edwards Lifesciences and Boston Scientific.

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

A new study offers early validation of the recently released Valve Academic Research Consortium 3 (VARC-3) definition of technical success after transcatheter aortic valve replacement (TAVR) and highlights its role in patient prognosis.

Results show that one in 10 patients (11.6%) undergoing TAVR with contemporary devices and techniques experiences technical failure, according to VARC-3.

At 30 days, patients with technical failure had significantly higher rates of the composite of cardiovascular (CV) death or stroke (11.5% vs. 3.5%), CV death (6.0% vs. 1.0%), and stroke (7.2% vs. 2.9%), compared with those with technical success.

Technical failure after TAVR was also independently associated with a twofold higher risk for CV death or stroke at 1 year (20.0% vs. 10.3%; hazard ratio, 2.01; 95% CI, 1.37-2.95).

Other independent predictors were history of peripheral artery disease (HR, 1.97), New York Heart Association III or IV disease (HR, 1.86), baseline moderate or greater mitral regurgitation (HR, 1.48), atrial fibrillation (HR, 1.40), and Society of Thoracic Surgeons predicted mortality risk (HR, 1.04).

“We were expecting that we were getting better over time with device iterations, with more experience, so we weren’t surprised by the result. But I think what is somewhat surprising is how much of an impact it has on the outcome,” senior study author Thomas Pilgrim, MD, Inselspital, University of Bern, Switzerland, told this news organization.

The VARC-3 document, introduced last year to some controversy, features a heavier focus on patient outcomes, as well as composite safety and efficacy endpoints. The definition of technical success after TAVR includes freedom from death; successful access, delivery of the device, and retrieval of the delivery system; correct positioning of a prosthetic heart valve into the proper anatomical location; and freedom from surgery or intervention related to the device or to an access-related or cardiac structural complication.

The composite endpoint is meant to replace the VARC-2 definition of “device success,” which also included freedom from death and correct valve positioning but required echocardiographic evaluation. With VARC-3, there is an “immediate measure” of success without having to wait for echocardiography, observed Dr. Pilgrim.

As reported in the Journal of the American College of Cardiology Cardiovascular Interventions, TAVR was a technical success in 1,435 of 1,624 (88.4%) patients. Technical failure occurred in 189 patients related to either vascular complications (8.6%) or procedural death or cardiac complications (3.0%).

The VARC-2 endpoint of device success was observed in 66.1% of patients. The high rate of device failure was largely attributed to a 28% incidence of prosthesis-patient mismatch.

“If you use the VARC-2 device success [definition], you include this patient–prosthesis mismatch, the [valve] gradients, [and] regurgitation and then device success is always lower,” Dr. Pilgrim said.

Asked whether the VARC-3 definition may be missing case failures, he replied: “At this stage, we don’t know how important these echocardiographic parameters are for hard clinical endpoints. Maybe the VARC-2 endpoint was too sensitive or the VARC-3 endpoint is not sensitive enough. This is something we just don’t know at this stage.”

Marco Barbanti, MD, an interventional cardiologist at Rodolico Polyclinic University Hospital-San Marco, Catania, Italy, and author of an accompanying editorial, said VARC-3 represents a more accurate indicator of immediate success of the procedure.

“It’s a more pertinent definition according to what really has an impact on prognosis, and, according to the results of this paper, actually, the calibration of this new definition is quite good,” Dr. Barbanti said in an interview.

Patients with VARC-3 technical failure were older, had a higher body mass index, and had more advanced heart failure symptoms than those with technical success. There were no significant differences between the two groups in echocardiographic or CT data, anesthetic strategy, valve type or size, or use of pre- or post-dilation.

All patients underwent TAVR with current balloon-expandable (Sapien 3/Sapien Ultra, Edwards Lifesciences) or self-expanding (Evolut R/PRO [Medtronic], Portico [Abbott], Symetis ACURATE/ACURATE neo [Boston Scientific]) devices between March 2012 and December 2019. A transfemoral approach was used in 92.5% of patients.

In a landmark analysis with the landmark set at 30 days, the effect of technical failure on adverse outcome was limited to the first 30 days (composite endpoint 0-30 days: HR, 3.42; P < .001; 30-360 days: HR, 1.36; P = .266; P for interaction = .002).

At 1 year, the composite of CV death and stroke endpoint occurred in 24.1% of patients with cardiac technical failure, in 18.8% of patients with vascular technical failure, and in 10.3% of patients with technical success.

In multivariate analyses, cardiac and vascular technical failures were independently associated with a 2.6-fold and 1.9-fold increased risk, respectively, for the composite of cardiovascular death and stroke at 1 year.

Female sex, larger device landing zone calcium volume, and earlier procedures (March 2012 to July 2016) were associated with a higher risk for cardiac technical failure, whereas, consistent with previous studies, higher body mass index and use of the Prostar/Manta versus the ProGlide closure device predicted vascular technical failure.

The findings “underscore that technical success is highly clinically relevant and may serve as one of the pivotal endpoints to evaluate the improvement of TAVR or for head-to-head comparisons of new devices in future clinical trials,” the authors conclude.

The findings reflect the experience of a single high-volume center with highly experienced operators in the prospective BERN TAVR registry, however, and may not be generalizable to other heart centers, they note. Although the registry has standardized follow-up, independent analysis of echocardiographic and CT, and independent event adjudication, vascular anatomy was not systematically assessed, and the potential exists for confounding from unmeasured variables.

Dr. Pilgrim reports research grants to the institution from Edwards Lifesciences, Boston Scientific, and Biotronik, personal fees from Biotronik and Boston Scientific, and other from HighLife SAS. Dr. Barbanti is a consultant for Edwards Lifesciences and Boston Scientific.

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

On the occasion of his 100th birthday, The Washington Post wrote of the trailblazing cardiologist and scientist Jeremiah Dr. Stamler, MD: “You may not know him, but he may have saved your life.”

Hyperbole, it was not.

Over a career spanning more than 70 years, Dr. Stamler transformed medicine and the public’s understanding of diet and lifestyle in cardiovascular health and helped introduce the concept of readily measured ‘risk factors’ such as cholesterol, hypertension, smoking, and diabetes.

Dr. Stamler, the founding chair and a professor emeritus of preventive medicine at Northwestern University’s Feinberg School of Medicine, Chicago, died Wednesday at his home in Sag Harbor, New York, at age 102.

“It is no exaggeration to say that few people in history have had as great an impact on human health,” Donald Lloyd-Jones, MD, chair of the department of preventive medicine at Feinberg and president of the American Heart Association, said in a statement.

“Jerry was a giant intellect who founded the fields of cardiovascular epidemiology and preventive cardiology and led [the way] in defining new prevention concepts right up until his last days,” Dr. Lloyd-Jones added in a statement issued by the university.

Tom Frieden, MD, former director of the Centers for Disease Control and Prevention, tweeted, “Jerry and my father did research on sodium together in the early 1950s. He was a giant in the field of public health, and we’re still benefiting from his brilliance and dedication.”

Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, tweeted, “R.I.P., Dr. Jeremiah Stamler, ‘the father of preventive cardiology,’ dies at 102 – a true legendary force for health.”

The son of Russian immigrants, Dr. Stamler was born in Brooklyn in 1919 and received a bachelor’s degree from Columbia University and a medical degree from State University of New York.

Discharged from the U.S. Army with the rank of captain, Dr. Stamler and his first wife, Rose, herself a distinguished cardiology researcher, moved to Chicago in 1947 and began researching nutrition and atherosclerosis under pioneering cardiology researcher Louis N. Katz, MD, ultimately showing that atherosclerosis could be introduced by changing the diet of chickens. She died in 1998.

Dr. Stamler also worked for Chicago’s Public Health Department in the 1950s, starting a rheumatic fever prevention program for children and the Chicago Coronary Prevention Evaluation Program, working with higher-risk middle-aged men.

Dr. Stamler’s international INTERSALT study established an independent relationship between blood pressure and increased sodium intake, as well as body mass index and heavy alcohol intake. First published in 1988, the research faced opposition from fellow scientists and the food industry alike.

In a 2006 interview, Dr. Stamler said he and fellow researchers began pressing the American Heart Association in the late 1950s to adopt a public policy of support to improve lifestyles, including smoking cessation and better nutrition. “It took some doing. The AHA was initially reluctant and was under pressure from industry.”

Their efforts were rewarded with the AHA’s first statement on smoking in 1959 and first statement on diet in 1960, whereas, Dr. Stamler noted, “the first World Health Organization statement did not come out until the 1980s.”

Philip Greenland, MD, professor of cardiology and former chair of preventive medicine at Northwestern, described Dr. Stamler as a “force for truth that never backed down when confronted by others who did not share his passion for truth and the best science.”

“I loved working with him since I always knew he would make our research better, clearer, more relevant, and more impactful,” he said in the AHA statement.

A lifelong activist and opponent of the Vietnam War, Dr. Stamler was subpoenaed in May 1965 by the House Un-American Activities Committee (HUAC) along with his nutritionist-assistant Yolanda Hall. Rather than pleading the Fifth Amendment against self-incrimination, Dr. Stamler and Ms. Hall refused to testify before the committee and were charged with contempt of Congress.

With the help of local attorneys, Dr. Stamler filed a civil suit against the HUAC, charging that its mandate was unconstitutional. After 8½ years of litigation that went all the way to the Supreme Court, the government agreed to drop its indictment against Dr. Stamler and he dropped his civil suit against the committee.

A year after the Stamler v. Willis case ended, the House voted to terminate the HUAC. In an essay detailing the high-profile case, Henry Blackburn quipped, “They simply did not know who they were taking on when they tagged ol’ Jerry Stamler.”

“Dr. Stamler’s exceptional science was paralleled by his remarkable humanity. He was a champion of our best American ideals, he was fearless when facing the status quo, and he was tireless in the pursuit of what was right and just. He remains a beacon for all that is noble in medicine,” said Clyde Yancy, MD, MSc, Northwestern’s chair of cardiology.

Over the course of his career, Dr. Stamler published more than 670 peer-reviewed papers, 22 books and monographs, and his work has been cited more than 56,000 times. A committed mentor, Dr. Stamler was the 2014 recipient of the AHA’s Eugene Braunwald Academic Mentorship Award.

A lifelong proponent of the Mediterranean diet, Dr. Stamler divided his time between New York, a home in Italy, and Chicago, with his wife Gloria Beckerman Stamler, whom he married in 2004 and who preceded him in death.

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

On the occasion of his 100th birthday, The Washington Post wrote of the trailblazing cardiologist and scientist Jeremiah Dr. Stamler, MD: “You may not know him, but he may have saved your life.”

Hyperbole, it was not.

Over a career spanning more than 70 years, Dr. Stamler transformed medicine and the public’s understanding of diet and lifestyle in cardiovascular health and helped introduce the concept of readily measured ‘risk factors’ such as cholesterol, hypertension, smoking, and diabetes.

Dr. Stamler, the founding chair and a professor emeritus of preventive medicine at Northwestern University’s Feinberg School of Medicine, Chicago, died Wednesday at his home in Sag Harbor, New York, at age 102.

“It is no exaggeration to say that few people in history have had as great an impact on human health,” Donald Lloyd-Jones, MD, chair of the department of preventive medicine at Feinberg and president of the American Heart Association, said in a statement.

“Jerry was a giant intellect who founded the fields of cardiovascular epidemiology and preventive cardiology and led [the way] in defining new prevention concepts right up until his last days,” Dr. Lloyd-Jones added in a statement issued by the university.

Tom Frieden, MD, former director of the Centers for Disease Control and Prevention, tweeted, “Jerry and my father did research on sodium together in the early 1950s. He was a giant in the field of public health, and we’re still benefiting from his brilliance and dedication.”

Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, tweeted, “R.I.P., Dr. Jeremiah Stamler, ‘the father of preventive cardiology,’ dies at 102 – a true legendary force for health.”

The son of Russian immigrants, Dr. Stamler was born in Brooklyn in 1919 and received a bachelor’s degree from Columbia University and a medical degree from State University of New York.

Discharged from the U.S. Army with the rank of captain, Dr. Stamler and his first wife, Rose, herself a distinguished cardiology researcher, moved to Chicago in 1947 and began researching nutrition and atherosclerosis under pioneering cardiology researcher Louis N. Katz, MD, ultimately showing that atherosclerosis could be introduced by changing the diet of chickens. She died in 1998.

Dr. Stamler also worked for Chicago’s Public Health Department in the 1950s, starting a rheumatic fever prevention program for children and the Chicago Coronary Prevention Evaluation Program, working with higher-risk middle-aged men.

Dr. Stamler’s international INTERSALT study established an independent relationship between blood pressure and increased sodium intake, as well as body mass index and heavy alcohol intake. First published in 1988, the research faced opposition from fellow scientists and the food industry alike.

In a 2006 interview, Dr. Stamler said he and fellow researchers began pressing the American Heart Association in the late 1950s to adopt a public policy of support to improve lifestyles, including smoking cessation and better nutrition. “It took some doing. The AHA was initially reluctant and was under pressure from industry.”

Their efforts were rewarded with the AHA’s first statement on smoking in 1959 and first statement on diet in 1960, whereas, Dr. Stamler noted, “the first World Health Organization statement did not come out until the 1980s.”

Philip Greenland, MD, professor of cardiology and former chair of preventive medicine at Northwestern, described Dr. Stamler as a “force for truth that never backed down when confronted by others who did not share his passion for truth and the best science.”

“I loved working with him since I always knew he would make our research better, clearer, more relevant, and more impactful,” he said in the AHA statement.

A lifelong activist and opponent of the Vietnam War, Dr. Stamler was subpoenaed in May 1965 by the House Un-American Activities Committee (HUAC) along with his nutritionist-assistant Yolanda Hall. Rather than pleading the Fifth Amendment against self-incrimination, Dr. Stamler and Ms. Hall refused to testify before the committee and were charged with contempt of Congress.

With the help of local attorneys, Dr. Stamler filed a civil suit against the HUAC, charging that its mandate was unconstitutional. After 8½ years of litigation that went all the way to the Supreme Court, the government agreed to drop its indictment against Dr. Stamler and he dropped his civil suit against the committee.

A year after the Stamler v. Willis case ended, the House voted to terminate the HUAC. In an essay detailing the high-profile case, Henry Blackburn quipped, “They simply did not know who they were taking on when they tagged ol’ Jerry Stamler.”

“Dr. Stamler’s exceptional science was paralleled by his remarkable humanity. He was a champion of our best American ideals, he was fearless when facing the status quo, and he was tireless in the pursuit of what was right and just. He remains a beacon for all that is noble in medicine,” said Clyde Yancy, MD, MSc, Northwestern’s chair of cardiology.

Over the course of his career, Dr. Stamler published more than 670 peer-reviewed papers, 22 books and monographs, and his work has been cited more than 56,000 times. A committed mentor, Dr. Stamler was the 2014 recipient of the AHA’s Eugene Braunwald Academic Mentorship Award.

A lifelong proponent of the Mediterranean diet, Dr. Stamler divided his time between New York, a home in Italy, and Chicago, with his wife Gloria Beckerman Stamler, whom he married in 2004 and who preceded him in death.

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

On the occasion of his 100th birthday, The Washington Post wrote of the trailblazing cardiologist and scientist Jeremiah Dr. Stamler, MD: “You may not know him, but he may have saved your life.”

Hyperbole, it was not.

Over a career spanning more than 70 years, Dr. Stamler transformed medicine and the public’s understanding of diet and lifestyle in cardiovascular health and helped introduce the concept of readily measured ‘risk factors’ such as cholesterol, hypertension, smoking, and diabetes.

Dr. Stamler, the founding chair and a professor emeritus of preventive medicine at Northwestern University’s Feinberg School of Medicine, Chicago, died Wednesday at his home in Sag Harbor, New York, at age 102.

“It is no exaggeration to say that few people in history have had as great an impact on human health,” Donald Lloyd-Jones, MD, chair of the department of preventive medicine at Feinberg and president of the American Heart Association, said in a statement.

“Jerry was a giant intellect who founded the fields of cardiovascular epidemiology and preventive cardiology and led [the way] in defining new prevention concepts right up until his last days,” Dr. Lloyd-Jones added in a statement issued by the university.

Tom Frieden, MD, former director of the Centers for Disease Control and Prevention, tweeted, “Jerry and my father did research on sodium together in the early 1950s. He was a giant in the field of public health, and we’re still benefiting from his brilliance and dedication.”

Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, tweeted, “R.I.P., Dr. Jeremiah Stamler, ‘the father of preventive cardiology,’ dies at 102 – a true legendary force for health.”

The son of Russian immigrants, Dr. Stamler was born in Brooklyn in 1919 and received a bachelor’s degree from Columbia University and a medical degree from State University of New York.

Discharged from the U.S. Army with the rank of captain, Dr. Stamler and his first wife, Rose, herself a distinguished cardiology researcher, moved to Chicago in 1947 and began researching nutrition and atherosclerosis under pioneering cardiology researcher Louis N. Katz, MD, ultimately showing that atherosclerosis could be introduced by changing the diet of chickens. She died in 1998.

Dr. Stamler also worked for Chicago’s Public Health Department in the 1950s, starting a rheumatic fever prevention program for children and the Chicago Coronary Prevention Evaluation Program, working with higher-risk middle-aged men.

Dr. Stamler’s international INTERSALT study established an independent relationship between blood pressure and increased sodium intake, as well as body mass index and heavy alcohol intake. First published in 1988, the research faced opposition from fellow scientists and the food industry alike.

In a 2006 interview, Dr. Stamler said he and fellow researchers began pressing the American Heart Association in the late 1950s to adopt a public policy of support to improve lifestyles, including smoking cessation and better nutrition. “It took some doing. The AHA was initially reluctant and was under pressure from industry.”

Their efforts were rewarded with the AHA’s first statement on smoking in 1959 and first statement on diet in 1960, whereas, Dr. Stamler noted, “the first World Health Organization statement did not come out until the 1980s.”

Philip Greenland, MD, professor of cardiology and former chair of preventive medicine at Northwestern, described Dr. Stamler as a “force for truth that never backed down when confronted by others who did not share his passion for truth and the best science.”

“I loved working with him since I always knew he would make our research better, clearer, more relevant, and more impactful,” he said in the AHA statement.

A lifelong activist and opponent of the Vietnam War, Dr. Stamler was subpoenaed in May 1965 by the House Un-American Activities Committee (HUAC) along with his nutritionist-assistant Yolanda Hall. Rather than pleading the Fifth Amendment against self-incrimination, Dr. Stamler and Ms. Hall refused to testify before the committee and were charged with contempt of Congress.

With the help of local attorneys, Dr. Stamler filed a civil suit against the HUAC, charging that its mandate was unconstitutional. After 8½ years of litigation that went all the way to the Supreme Court, the government agreed to drop its indictment against Dr. Stamler and he dropped his civil suit against the committee.

A year after the Stamler v. Willis case ended, the House voted to terminate the HUAC. In an essay detailing the high-profile case, Henry Blackburn quipped, “They simply did not know who they were taking on when they tagged ol’ Jerry Stamler.”

“Dr. Stamler’s exceptional science was paralleled by his remarkable humanity. He was a champion of our best American ideals, he was fearless when facing the status quo, and he was tireless in the pursuit of what was right and just. He remains a beacon for all that is noble in medicine,” said Clyde Yancy, MD, MSc, Northwestern’s chair of cardiology.

Over the course of his career, Dr. Stamler published more than 670 peer-reviewed papers, 22 books and monographs, and his work has been cited more than 56,000 times. A committed mentor, Dr. Stamler was the 2014 recipient of the AHA’s Eugene Braunwald Academic Mentorship Award.

A lifelong proponent of the Mediterranean diet, Dr. Stamler divided his time between New York, a home in Italy, and Chicago, with his wife Gloria Beckerman Stamler, whom he married in 2004 and who preceded him in death.

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