User login
Physiological versus pathological cardiac remodeling in athletes
SNOWMASS, COLO. – according to Matthew W. Martinez, MD, medical director of the Sports Cardiology and Hypertrophic Cardiomyopathy Center at the Lehigh Valley Health Network in Allentown, Pa.
“The MRI may be the single test that best helps you sort out when you’re not quite sure. If you think about a single study that’s going to help you identify cardiac arrest etiologies – hypertrophic cardiomyopathy, myocarditis, anomalous coronaries, left-sided disease, right-sided disease like arrhythmogenic right ventricular cardiomyopathy, valvular heart disease, aortic disease – MRI is a very powerful tool because it will help you evaluate all of those groups more than 90% of the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Dr. Martinez, who serves as lead cardiologist for U.S. Major League Soccer and is also heavily involved with the National Football League, spends a lot of time with elite professional or Olympic athletes who fall into what he calls “the gray zone,” with a left ventricular wall thickness of 12-15 mm as measured on echocardiography. While that would clearly be considered abnormal in a nonathlete or a recreational sports enthusiast, his experience as well as that of other sports cardiologists working with professional soccer, football, and basketball players, bicyclists, and high-level track and field competitors has been that wall thickness in the 12- to 15-mm range in elite athletes can represent physiological adaptation to their enormous cardiovascular workloads. For example, more than 10% of National Football League players have a maximum left ventricular wall thickness of 13 mm or more, as do more than 10% of National Basketball Association players.
But what if that echocardiographic measurement of wall thickness is off by a millimeter or two, as is often par for the course?
“It’s well described that MRI gives a better look at wall thickness than echocardiography, especially where there’s areas of hypertrophy next to normal wall. In that gray zone, where we have to know if it’s really 10-12 or 14-16 mm, the MRI better identifies the actual thickness,” he said.
In addition, cardiac MRI readily provides accurate, reproducible measurements of left and right ventricular chamber size. But the most important way in which cardiac MRI helps in evaluating the significance of cardiac remodeling in athletes is via the gadolinium study. Late gadolinium enhancement is a concerning finding. It indicates the presence of myocardial fibrosis and scar, which at least in the general population is a prognostic sign for worse outcome.
“If you detect fibrosis, the search for pathology has to start,” the cardiologist emphasized.
He noted that the most comprehensive review to date of myocardial fibrosis in endurance athletes identified the intraventricular septum and the junction of the right ventricle and septum as the most common sites of involvement. The investigators concluded that, while there is a lack of compelling data on the clinical impact and prognosis of myocardial fibrosis in athletes, potential mechanisms include exercise-induced repetitive microinjury, pulmonary artery pressure overload, genetic predisposition, and silent myocarditis (Mayo Clin Proc. 2016 Nov;91[11]:1617-31).
That being said about the value of cardiac MRI as a tiebreaker, Dr. Martinez asserted that “there’s no specific test that’s going to get you out of jail. ... I would submit to you that you have to load the boat. Be comprehensive and try to build a case for one side or the other. And I would encourage you to ask for help; we do it all the time.”
Dilated chambers outside the normal range are common in competitive athletes. Don’t accept the echocardiographic hard numeric cutoffs that have been established as “normal” in the general population. For example, 36% of National Basketball Association players have a left ventricular end diastolic dimension (LVEDD) greater than 60 mm.
“I’ve seen LVEDDs up to 70 mm in cyclists. And all but a handful have a normal left ventricular ejection fraction greater than 50%,” he noted.
Dilated chambers in elite athletes are reassuring, provided stroke volume is preserved or, as is more often the case, enhanced.
“One of the hallmarks of being an athlete is the ability to suck in blood and increase stroke volume as a result. A typical stroke volume in an athlete is well above normal, with 85-90 cc or more being common. On tissue Doppler assessment, you shouldn’t have a normal inflow pattern or normal relaxation. A septal E prime velocity of 11-14 cm/sec is what I typically expect in an athlete. A lower E prime velocity suggests early pathologic change. If you find an E prime velocity of less than 9 cm/sec on tissue Doppler, or an elevated filling pressure like 15 mm Hg, that correlates with a greater than 90% sensitivity for pathology, such as hypertrophic cardiomyopathy. The average E prime velocity in Major League Soccer players is about 13 cm/sec, so that’s an important number to keep in your head,” according to the cardiologist.
Cardiac remodeling in elite athletes tends towards one of two forms, depending upon their sport. Endurance athletes, such as marathon runners, are repetitively volume challenged, so expect a tendency towards aortic regurgitation. For pressure-challenged athletes, such as power weightlifters, the tendency is toward aortic stenosis.
“But also expect a blend. It’s rarely just one or the other. Understanding that can help you discern the gray zone athlete,” he said.
Dr. Martinez reported having no financial conflicts of interest regarding his presentation.
SNOWMASS, COLO. – according to Matthew W. Martinez, MD, medical director of the Sports Cardiology and Hypertrophic Cardiomyopathy Center at the Lehigh Valley Health Network in Allentown, Pa.
“The MRI may be the single test that best helps you sort out when you’re not quite sure. If you think about a single study that’s going to help you identify cardiac arrest etiologies – hypertrophic cardiomyopathy, myocarditis, anomalous coronaries, left-sided disease, right-sided disease like arrhythmogenic right ventricular cardiomyopathy, valvular heart disease, aortic disease – MRI is a very powerful tool because it will help you evaluate all of those groups more than 90% of the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Dr. Martinez, who serves as lead cardiologist for U.S. Major League Soccer and is also heavily involved with the National Football League, spends a lot of time with elite professional or Olympic athletes who fall into what he calls “the gray zone,” with a left ventricular wall thickness of 12-15 mm as measured on echocardiography. While that would clearly be considered abnormal in a nonathlete or a recreational sports enthusiast, his experience as well as that of other sports cardiologists working with professional soccer, football, and basketball players, bicyclists, and high-level track and field competitors has been that wall thickness in the 12- to 15-mm range in elite athletes can represent physiological adaptation to their enormous cardiovascular workloads. For example, more than 10% of National Football League players have a maximum left ventricular wall thickness of 13 mm or more, as do more than 10% of National Basketball Association players.
But what if that echocardiographic measurement of wall thickness is off by a millimeter or two, as is often par for the course?
“It’s well described that MRI gives a better look at wall thickness than echocardiography, especially where there’s areas of hypertrophy next to normal wall. In that gray zone, where we have to know if it’s really 10-12 or 14-16 mm, the MRI better identifies the actual thickness,” he said.
In addition, cardiac MRI readily provides accurate, reproducible measurements of left and right ventricular chamber size. But the most important way in which cardiac MRI helps in evaluating the significance of cardiac remodeling in athletes is via the gadolinium study. Late gadolinium enhancement is a concerning finding. It indicates the presence of myocardial fibrosis and scar, which at least in the general population is a prognostic sign for worse outcome.
“If you detect fibrosis, the search for pathology has to start,” the cardiologist emphasized.
He noted that the most comprehensive review to date of myocardial fibrosis in endurance athletes identified the intraventricular septum and the junction of the right ventricle and septum as the most common sites of involvement. The investigators concluded that, while there is a lack of compelling data on the clinical impact and prognosis of myocardial fibrosis in athletes, potential mechanisms include exercise-induced repetitive microinjury, pulmonary artery pressure overload, genetic predisposition, and silent myocarditis (Mayo Clin Proc. 2016 Nov;91[11]:1617-31).
That being said about the value of cardiac MRI as a tiebreaker, Dr. Martinez asserted that “there’s no specific test that’s going to get you out of jail. ... I would submit to you that you have to load the boat. Be comprehensive and try to build a case for one side or the other. And I would encourage you to ask for help; we do it all the time.”
Dilated chambers outside the normal range are common in competitive athletes. Don’t accept the echocardiographic hard numeric cutoffs that have been established as “normal” in the general population. For example, 36% of National Basketball Association players have a left ventricular end diastolic dimension (LVEDD) greater than 60 mm.
“I’ve seen LVEDDs up to 70 mm in cyclists. And all but a handful have a normal left ventricular ejection fraction greater than 50%,” he noted.
Dilated chambers in elite athletes are reassuring, provided stroke volume is preserved or, as is more often the case, enhanced.
“One of the hallmarks of being an athlete is the ability to suck in blood and increase stroke volume as a result. A typical stroke volume in an athlete is well above normal, with 85-90 cc or more being common. On tissue Doppler assessment, you shouldn’t have a normal inflow pattern or normal relaxation. A septal E prime velocity of 11-14 cm/sec is what I typically expect in an athlete. A lower E prime velocity suggests early pathologic change. If you find an E prime velocity of less than 9 cm/sec on tissue Doppler, or an elevated filling pressure like 15 mm Hg, that correlates with a greater than 90% sensitivity for pathology, such as hypertrophic cardiomyopathy. The average E prime velocity in Major League Soccer players is about 13 cm/sec, so that’s an important number to keep in your head,” according to the cardiologist.
Cardiac remodeling in elite athletes tends towards one of two forms, depending upon their sport. Endurance athletes, such as marathon runners, are repetitively volume challenged, so expect a tendency towards aortic regurgitation. For pressure-challenged athletes, such as power weightlifters, the tendency is toward aortic stenosis.
“But also expect a blend. It’s rarely just one or the other. Understanding that can help you discern the gray zone athlete,” he said.
Dr. Martinez reported having no financial conflicts of interest regarding his presentation.
SNOWMASS, COLO. – according to Matthew W. Martinez, MD, medical director of the Sports Cardiology and Hypertrophic Cardiomyopathy Center at the Lehigh Valley Health Network in Allentown, Pa.
“The MRI may be the single test that best helps you sort out when you’re not quite sure. If you think about a single study that’s going to help you identify cardiac arrest etiologies – hypertrophic cardiomyopathy, myocarditis, anomalous coronaries, left-sided disease, right-sided disease like arrhythmogenic right ventricular cardiomyopathy, valvular heart disease, aortic disease – MRI is a very powerful tool because it will help you evaluate all of those groups more than 90% of the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Dr. Martinez, who serves as lead cardiologist for U.S. Major League Soccer and is also heavily involved with the National Football League, spends a lot of time with elite professional or Olympic athletes who fall into what he calls “the gray zone,” with a left ventricular wall thickness of 12-15 mm as measured on echocardiography. While that would clearly be considered abnormal in a nonathlete or a recreational sports enthusiast, his experience as well as that of other sports cardiologists working with professional soccer, football, and basketball players, bicyclists, and high-level track and field competitors has been that wall thickness in the 12- to 15-mm range in elite athletes can represent physiological adaptation to their enormous cardiovascular workloads. For example, more than 10% of National Football League players have a maximum left ventricular wall thickness of 13 mm or more, as do more than 10% of National Basketball Association players.
But what if that echocardiographic measurement of wall thickness is off by a millimeter or two, as is often par for the course?
“It’s well described that MRI gives a better look at wall thickness than echocardiography, especially where there’s areas of hypertrophy next to normal wall. In that gray zone, where we have to know if it’s really 10-12 or 14-16 mm, the MRI better identifies the actual thickness,” he said.
In addition, cardiac MRI readily provides accurate, reproducible measurements of left and right ventricular chamber size. But the most important way in which cardiac MRI helps in evaluating the significance of cardiac remodeling in athletes is via the gadolinium study. Late gadolinium enhancement is a concerning finding. It indicates the presence of myocardial fibrosis and scar, which at least in the general population is a prognostic sign for worse outcome.
“If you detect fibrosis, the search for pathology has to start,” the cardiologist emphasized.
He noted that the most comprehensive review to date of myocardial fibrosis in endurance athletes identified the intraventricular septum and the junction of the right ventricle and septum as the most common sites of involvement. The investigators concluded that, while there is a lack of compelling data on the clinical impact and prognosis of myocardial fibrosis in athletes, potential mechanisms include exercise-induced repetitive microinjury, pulmonary artery pressure overload, genetic predisposition, and silent myocarditis (Mayo Clin Proc. 2016 Nov;91[11]:1617-31).
That being said about the value of cardiac MRI as a tiebreaker, Dr. Martinez asserted that “there’s no specific test that’s going to get you out of jail. ... I would submit to you that you have to load the boat. Be comprehensive and try to build a case for one side or the other. And I would encourage you to ask for help; we do it all the time.”
Dilated chambers outside the normal range are common in competitive athletes. Don’t accept the echocardiographic hard numeric cutoffs that have been established as “normal” in the general population. For example, 36% of National Basketball Association players have a left ventricular end diastolic dimension (LVEDD) greater than 60 mm.
“I’ve seen LVEDDs up to 70 mm in cyclists. And all but a handful have a normal left ventricular ejection fraction greater than 50%,” he noted.
Dilated chambers in elite athletes are reassuring, provided stroke volume is preserved or, as is more often the case, enhanced.
“One of the hallmarks of being an athlete is the ability to suck in blood and increase stroke volume as a result. A typical stroke volume in an athlete is well above normal, with 85-90 cc or more being common. On tissue Doppler assessment, you shouldn’t have a normal inflow pattern or normal relaxation. A septal E prime velocity of 11-14 cm/sec is what I typically expect in an athlete. A lower E prime velocity suggests early pathologic change. If you find an E prime velocity of less than 9 cm/sec on tissue Doppler, or an elevated filling pressure like 15 mm Hg, that correlates with a greater than 90% sensitivity for pathology, such as hypertrophic cardiomyopathy. The average E prime velocity in Major League Soccer players is about 13 cm/sec, so that’s an important number to keep in your head,” according to the cardiologist.
Cardiac remodeling in elite athletes tends towards one of two forms, depending upon their sport. Endurance athletes, such as marathon runners, are repetitively volume challenged, so expect a tendency towards aortic regurgitation. For pressure-challenged athletes, such as power weightlifters, the tendency is toward aortic stenosis.
“But also expect a blend. It’s rarely just one or the other. Understanding that can help you discern the gray zone athlete,” he said.
Dr. Martinez reported having no financial conflicts of interest regarding his presentation.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Consider adopting the MESA 10-year CHD risk calculator
SNOWMASS, COLO. – The Multi-Ethnic Study of Atherosclerosis–based 10-year coronary heart disease risk calculator offers significant advantages over the far more widely used Atherosclerotic Cardiovascular Disease risk estimator based upon the pooled cohort equations recommended in the American College of Cardiology/American Heart Association guidelines, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I don’t use the PCE very much. I use the MESA [Multi-Ethnic Study of Atherosclerosis]. I like it because it gives me options I don’t have with the PCE [pooled cohort equations],” Dr. Vogel, a preventive cardiology expert at the University of Colorado at Denver, Aurora, said at the meeting sponsored by the American College of Cardiology.
Those added options include, importantly, the ability to plug in a patient’s coronary artery calcium score. MESA, a landmark longitudinal National Institutes of Health–sponsored study, generated a great deal of the data that established the prognostic value of measuring coronary artery calcium.
“You can do the MESA worksheet with or without coronary artery calcium, either way,” Dr. Vogel noted.
Another big advantage for the MESA risk calculator: It asks a yes/no question about family history of heart attack in first-degree relatives. That’s truly risk-altering information, and yet it’s absent from the ACC/AHA ASCVD (Atherosclerotic Cardiovascular Disease) risk calculator, the cardiologist continued.
Plus, the MESA risk calculator includes four ethnic options: Caucasian, African American, Chinese, or Hispanic, while the ACC/AHA’s PCE-based tool includes only the categories of white, African American, or other.
Dr. Vogel offered a case example for purposes of comparison and contrast of the two risk calculators: a 48-year-old white man with no history or symptoms of cardiovascular disease whose father had an MI at age 52. He wants to know whether he should start taking a statin. The patient is a former smoker who quit 3 years ago. His physical exam is normal. He has a body mass index of 29 kg/m2, an LDL cholesterol of 134 mg/dL, a total cholesterol of 194 mg/dL, a triglyceride level of 92 mg/dL, blood pressure of 128/78 mm Hg, an HDL cholesterol of 42 mg/dL, and a hemoglobin A1c of 5.9%.
Using the PCE-based risk calculator, the man’s 10-year risk of cardiovascular disease is only 3.3%, which falls below the ACC/AHA guideline-recommended threshold for statin therapy for primary prevention. But with the MESA score, as a result of the additional information regarding the family history of premature cardiovascular disease, the patient’s risk jumps to 4.9%, even without including a coronary artery calcium score.
“This shows you how big a factor the family history is. I think it’s unfortunate that the PCE doesn’t put it in,” Dr. Vogel said.
Indeed, in an analysis from MESA, a 60-year-old man with a lipid and blood pressure profile similar to that of Dr. Vogel’s patient would have a 10-year cardiovascular disease risk of 6% with a negative family history and a 9% risk with a positive history, he noted.
In the 48-year-old patient used as an example by Dr. Vogel, plugging into the MESA risk calculator a coronary artery calcium score of, say, 50, 100, or 150 Agatston units would boost the 10-year cardiovascular disease risk to 7.5%, 8.9%, and 9.9%, respectively.
Both the MESA and the ACC/AHA risk calculators incorporate diabetes as a simple yes/no item. It’s either present or absent. This is too crude a dichotomy for Dr. Vogel’s liking in light of data showing that individuals with impaired glucose tolerance have a cumulative risk of cardiovascular mortality that’s intermediate between diabetic and normoglycemic individuals. And of course, the patient in his case example had a HbA1c of 5.9%. So what is a physician to do?
“I fudge the numbers,” he said. “
He also adjusts a former smoker’s estimated 10-year cardiovascular risk based upon how long ago the smoker quit. An ex-smoker’s hazard ratio for coronary heart disease doesn’t drop to that of a never-smoker until 8 years after quitting. And since the patient in this example has been tobacco-free for only 3 years, Dr. Vogel bumps up that individual’s risk level once again. So at this point, even without the additional information that would be provided by a coronary calcium score, the patient’s adjusted MESA 10-year risk is in the 10% range, compared with the 3.3% figure derived using the PCE-based risk calculator.
He reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center, receiving research grants from Sanofi, and serving on speakers bureaus for Regeneron and Sanofi.
SNOWMASS, COLO. – The Multi-Ethnic Study of Atherosclerosis–based 10-year coronary heart disease risk calculator offers significant advantages over the far more widely used Atherosclerotic Cardiovascular Disease risk estimator based upon the pooled cohort equations recommended in the American College of Cardiology/American Heart Association guidelines, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I don’t use the PCE very much. I use the MESA [Multi-Ethnic Study of Atherosclerosis]. I like it because it gives me options I don’t have with the PCE [pooled cohort equations],” Dr. Vogel, a preventive cardiology expert at the University of Colorado at Denver, Aurora, said at the meeting sponsored by the American College of Cardiology.
Those added options include, importantly, the ability to plug in a patient’s coronary artery calcium score. MESA, a landmark longitudinal National Institutes of Health–sponsored study, generated a great deal of the data that established the prognostic value of measuring coronary artery calcium.
“You can do the MESA worksheet with or without coronary artery calcium, either way,” Dr. Vogel noted.
Another big advantage for the MESA risk calculator: It asks a yes/no question about family history of heart attack in first-degree relatives. That’s truly risk-altering information, and yet it’s absent from the ACC/AHA ASCVD (Atherosclerotic Cardiovascular Disease) risk calculator, the cardiologist continued.
Plus, the MESA risk calculator includes four ethnic options: Caucasian, African American, Chinese, or Hispanic, while the ACC/AHA’s PCE-based tool includes only the categories of white, African American, or other.
Dr. Vogel offered a case example for purposes of comparison and contrast of the two risk calculators: a 48-year-old white man with no history or symptoms of cardiovascular disease whose father had an MI at age 52. He wants to know whether he should start taking a statin. The patient is a former smoker who quit 3 years ago. His physical exam is normal. He has a body mass index of 29 kg/m2, an LDL cholesterol of 134 mg/dL, a total cholesterol of 194 mg/dL, a triglyceride level of 92 mg/dL, blood pressure of 128/78 mm Hg, an HDL cholesterol of 42 mg/dL, and a hemoglobin A1c of 5.9%.
Using the PCE-based risk calculator, the man’s 10-year risk of cardiovascular disease is only 3.3%, which falls below the ACC/AHA guideline-recommended threshold for statin therapy for primary prevention. But with the MESA score, as a result of the additional information regarding the family history of premature cardiovascular disease, the patient’s risk jumps to 4.9%, even without including a coronary artery calcium score.
“This shows you how big a factor the family history is. I think it’s unfortunate that the PCE doesn’t put it in,” Dr. Vogel said.
Indeed, in an analysis from MESA, a 60-year-old man with a lipid and blood pressure profile similar to that of Dr. Vogel’s patient would have a 10-year cardiovascular disease risk of 6% with a negative family history and a 9% risk with a positive history, he noted.
In the 48-year-old patient used as an example by Dr. Vogel, plugging into the MESA risk calculator a coronary artery calcium score of, say, 50, 100, or 150 Agatston units would boost the 10-year cardiovascular disease risk to 7.5%, 8.9%, and 9.9%, respectively.
Both the MESA and the ACC/AHA risk calculators incorporate diabetes as a simple yes/no item. It’s either present or absent. This is too crude a dichotomy for Dr. Vogel’s liking in light of data showing that individuals with impaired glucose tolerance have a cumulative risk of cardiovascular mortality that’s intermediate between diabetic and normoglycemic individuals. And of course, the patient in his case example had a HbA1c of 5.9%. So what is a physician to do?
“I fudge the numbers,” he said. “
He also adjusts a former smoker’s estimated 10-year cardiovascular risk based upon how long ago the smoker quit. An ex-smoker’s hazard ratio for coronary heart disease doesn’t drop to that of a never-smoker until 8 years after quitting. And since the patient in this example has been tobacco-free for only 3 years, Dr. Vogel bumps up that individual’s risk level once again. So at this point, even without the additional information that would be provided by a coronary calcium score, the patient’s adjusted MESA 10-year risk is in the 10% range, compared with the 3.3% figure derived using the PCE-based risk calculator.
He reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center, receiving research grants from Sanofi, and serving on speakers bureaus for Regeneron and Sanofi.
SNOWMASS, COLO. – The Multi-Ethnic Study of Atherosclerosis–based 10-year coronary heart disease risk calculator offers significant advantages over the far more widely used Atherosclerotic Cardiovascular Disease risk estimator based upon the pooled cohort equations recommended in the American College of Cardiology/American Heart Association guidelines, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I don’t use the PCE very much. I use the MESA [Multi-Ethnic Study of Atherosclerosis]. I like it because it gives me options I don’t have with the PCE [pooled cohort equations],” Dr. Vogel, a preventive cardiology expert at the University of Colorado at Denver, Aurora, said at the meeting sponsored by the American College of Cardiology.
Those added options include, importantly, the ability to plug in a patient’s coronary artery calcium score. MESA, a landmark longitudinal National Institutes of Health–sponsored study, generated a great deal of the data that established the prognostic value of measuring coronary artery calcium.
“You can do the MESA worksheet with or without coronary artery calcium, either way,” Dr. Vogel noted.
Another big advantage for the MESA risk calculator: It asks a yes/no question about family history of heart attack in first-degree relatives. That’s truly risk-altering information, and yet it’s absent from the ACC/AHA ASCVD (Atherosclerotic Cardiovascular Disease) risk calculator, the cardiologist continued.
Plus, the MESA risk calculator includes four ethnic options: Caucasian, African American, Chinese, or Hispanic, while the ACC/AHA’s PCE-based tool includes only the categories of white, African American, or other.
Dr. Vogel offered a case example for purposes of comparison and contrast of the two risk calculators: a 48-year-old white man with no history or symptoms of cardiovascular disease whose father had an MI at age 52. He wants to know whether he should start taking a statin. The patient is a former smoker who quit 3 years ago. His physical exam is normal. He has a body mass index of 29 kg/m2, an LDL cholesterol of 134 mg/dL, a total cholesterol of 194 mg/dL, a triglyceride level of 92 mg/dL, blood pressure of 128/78 mm Hg, an HDL cholesterol of 42 mg/dL, and a hemoglobin A1c of 5.9%.
Using the PCE-based risk calculator, the man’s 10-year risk of cardiovascular disease is only 3.3%, which falls below the ACC/AHA guideline-recommended threshold for statin therapy for primary prevention. But with the MESA score, as a result of the additional information regarding the family history of premature cardiovascular disease, the patient’s risk jumps to 4.9%, even without including a coronary artery calcium score.
“This shows you how big a factor the family history is. I think it’s unfortunate that the PCE doesn’t put it in,” Dr. Vogel said.
Indeed, in an analysis from MESA, a 60-year-old man with a lipid and blood pressure profile similar to that of Dr. Vogel’s patient would have a 10-year cardiovascular disease risk of 6% with a negative family history and a 9% risk with a positive history, he noted.
In the 48-year-old patient used as an example by Dr. Vogel, plugging into the MESA risk calculator a coronary artery calcium score of, say, 50, 100, or 150 Agatston units would boost the 10-year cardiovascular disease risk to 7.5%, 8.9%, and 9.9%, respectively.
Both the MESA and the ACC/AHA risk calculators incorporate diabetes as a simple yes/no item. It’s either present or absent. This is too crude a dichotomy for Dr. Vogel’s liking in light of data showing that individuals with impaired glucose tolerance have a cumulative risk of cardiovascular mortality that’s intermediate between diabetic and normoglycemic individuals. And of course, the patient in his case example had a HbA1c of 5.9%. So what is a physician to do?
“I fudge the numbers,” he said. “
He also adjusts a former smoker’s estimated 10-year cardiovascular risk based upon how long ago the smoker quit. An ex-smoker’s hazard ratio for coronary heart disease doesn’t drop to that of a never-smoker until 8 years after quitting. And since the patient in this example has been tobacco-free for only 3 years, Dr. Vogel bumps up that individual’s risk level once again. So at this point, even without the additional information that would be provided by a coronary calcium score, the patient’s adjusted MESA 10-year risk is in the 10% range, compared with the 3.3% figure derived using the PCE-based risk calculator.
He reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center, receiving research grants from Sanofi, and serving on speakers bureaus for Regeneron and Sanofi.
REPORTING FROM ACC SNOWMASS 2019
How to get surgical-like results using MitraClip
SNOWMASS, COLO. – Achieving optimal surgical-like results via transcatheter repair of primary mitral regurgitation using the MitraClip in prohibitively high-surgical-risk patients becomes much more likely by taking into account key predictive anatomic and procedural features as well as the major comorbidities influencing outcome, Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
. Dr. Sorajja was first author of a study of 1-year outcomes in 2,952 patients with MR in the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry (STS/ACC TVT) who were commercially treated with the MitraClip, at present the only transcatheter device approved for this indication. Sixty-two percent had a surgical-like result, and their 1-year mortality rate of 21.7% was significantly lower than the 29.2% rate for patients with residual grade 2 MR and the 48.9% mortality in patients left with grade 3 or 4 MR.
It’s noteworthy that even though the acute procedural success rate – defined as residual grade 2 or less MR – was impressively high at 91.8% in this group of nearly 3,000 patients, roughly one in five in the overall series was rehospitalized for heart failure within 1 year, and one in four was dead. So there remains considerable room for improvement in long-term outcomes of transcatheter repair of MR, said Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute.
Anatomic predictors of good short-term outcome
“There are specific anatomic criteria, but an easier way to think about whether your patient could get an optimal result is to remember the physical limits of this therapy. What I teach is 1-2-5-50: the MitraClip device is about 1 cm tall, about 2 cm wide, and you need about 5 mm of leaflet inside the clip to create coaptation for MR reduction. And if you do that, you will reduce the mitral valve area by about 50%, so you have to be very careful in patients with small valve areas because you can worsen mitral stenosis,” the cardiologist explained.
Only two transechocardiographic views are needed to know if a patient will have a good result with the MitraClip. A bicommissural view traversing the valve medial to lateral shows where the MR jet is; if it’s in the middle of the mitral valve, that’s favorable because it means the interventionalist has a lot of freedom to operate. Then, going orthogonal from the bicommissural view to get an anterior-posterior view allows the operator to get a good look at the valve leaflets and apply the 1-2-5 rule to determine if the leaflet approximation is favorable, he continued.
Some mitral valve anatomy variants make it challenging to get surgical-like results with a transcatheter repair. These include calcified leaflets, large gaps between leaflets, Barlow’s valves, and small leaflets. Be aware of key success-limiting comorbidities.
In the STS/ACC TVT registry study, severe tricuspid regurgitation, present in 10% of patients preprocedurally, virtually doubled the adjusted risk of 1-year mortality in multivariate analyses.
“Tricuspid regurgitation is one of the most common concomitant lesions. And the presence of tricuspid regurgitation is ominous,” Dr. Sorajja said. “Treatment of concomitant lesions such as this is going to be necessary for us to get a truly surgical-like result in outcomes.”
Toward this end, he put in a plug to consider referring patients with severe tricuspid regurgitation for enrollment in the TRILUMINATE II trial, the pivotal U.S. trial for the investigational Tri-Clip device for transcatheter tricuspid valve repair, for which he is coprincipal investigator. The trial, pitting the Tri-Clip against medical therapy, is due to start in the spring of 2019.
In multivariate analyses of the MitraClip registry study, other predictors of the combined endpoint of death and rehospitalization for heart failure at 1 year, in addition to severe tricuspid regurgitation, included dialysis, with an adjusted 2.09-fold increased risk; moderate or severe lung disease, with a 1.28-fold risk; postprocedural residual MR; diminished left ventricular ejection fraction; and advanced age (J Am Coll Cardiol. 2017 Nov 7;70[19]:2315-27).
Case experience counts
In a soon-to-be-published more up-to-date analysis of more than 12,000 MitraClip patients in the STS/ACC TVT registry, which captures all U.S. commercial use of the device for its approved indication, Dr. Sorajja and his coinvestigators documented a procedural truism: The more cases an interventionalist performs, the better the results. However, even inexperienced users of the MitraClip were able to obtain at least moderate results – that is, residual grade 2 or less MR – 90% of the time or more.
“There is some change with greater experience, but it’s actually quite small,” according to Dr. Sorajja.
However, optimal results – grade 0 or 1 MR – are another matter entirely.
“For grade 1 or less, the learning curve is much steeper. It plateaus somewhere between 50 and 75 cases. In other words, in most cases you can get to moderate MR, but getting to grade 1 requires more experience. That relationship between case experience and outcome also applies to complication rates and case time,” he said.
Although at present the MitraClip is the only Food and Drug Administration–approved transcatheter device for MR repair, there are many others in the developmental pipeline, the he noted.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Achieving optimal surgical-like results via transcatheter repair of primary mitral regurgitation using the MitraClip in prohibitively high-surgical-risk patients becomes much more likely by taking into account key predictive anatomic and procedural features as well as the major comorbidities influencing outcome, Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
. Dr. Sorajja was first author of a study of 1-year outcomes in 2,952 patients with MR in the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry (STS/ACC TVT) who were commercially treated with the MitraClip, at present the only transcatheter device approved for this indication. Sixty-two percent had a surgical-like result, and their 1-year mortality rate of 21.7% was significantly lower than the 29.2% rate for patients with residual grade 2 MR and the 48.9% mortality in patients left with grade 3 or 4 MR.
It’s noteworthy that even though the acute procedural success rate – defined as residual grade 2 or less MR – was impressively high at 91.8% in this group of nearly 3,000 patients, roughly one in five in the overall series was rehospitalized for heart failure within 1 year, and one in four was dead. So there remains considerable room for improvement in long-term outcomes of transcatheter repair of MR, said Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute.
Anatomic predictors of good short-term outcome
“There are specific anatomic criteria, but an easier way to think about whether your patient could get an optimal result is to remember the physical limits of this therapy. What I teach is 1-2-5-50: the MitraClip device is about 1 cm tall, about 2 cm wide, and you need about 5 mm of leaflet inside the clip to create coaptation for MR reduction. And if you do that, you will reduce the mitral valve area by about 50%, so you have to be very careful in patients with small valve areas because you can worsen mitral stenosis,” the cardiologist explained.
Only two transechocardiographic views are needed to know if a patient will have a good result with the MitraClip. A bicommissural view traversing the valve medial to lateral shows where the MR jet is; if it’s in the middle of the mitral valve, that’s favorable because it means the interventionalist has a lot of freedom to operate. Then, going orthogonal from the bicommissural view to get an anterior-posterior view allows the operator to get a good look at the valve leaflets and apply the 1-2-5 rule to determine if the leaflet approximation is favorable, he continued.
Some mitral valve anatomy variants make it challenging to get surgical-like results with a transcatheter repair. These include calcified leaflets, large gaps between leaflets, Barlow’s valves, and small leaflets. Be aware of key success-limiting comorbidities.
In the STS/ACC TVT registry study, severe tricuspid regurgitation, present in 10% of patients preprocedurally, virtually doubled the adjusted risk of 1-year mortality in multivariate analyses.
“Tricuspid regurgitation is one of the most common concomitant lesions. And the presence of tricuspid regurgitation is ominous,” Dr. Sorajja said. “Treatment of concomitant lesions such as this is going to be necessary for us to get a truly surgical-like result in outcomes.”
Toward this end, he put in a plug to consider referring patients with severe tricuspid regurgitation for enrollment in the TRILUMINATE II trial, the pivotal U.S. trial for the investigational Tri-Clip device for transcatheter tricuspid valve repair, for which he is coprincipal investigator. The trial, pitting the Tri-Clip against medical therapy, is due to start in the spring of 2019.
In multivariate analyses of the MitraClip registry study, other predictors of the combined endpoint of death and rehospitalization for heart failure at 1 year, in addition to severe tricuspid regurgitation, included dialysis, with an adjusted 2.09-fold increased risk; moderate or severe lung disease, with a 1.28-fold risk; postprocedural residual MR; diminished left ventricular ejection fraction; and advanced age (J Am Coll Cardiol. 2017 Nov 7;70[19]:2315-27).
Case experience counts
In a soon-to-be-published more up-to-date analysis of more than 12,000 MitraClip patients in the STS/ACC TVT registry, which captures all U.S. commercial use of the device for its approved indication, Dr. Sorajja and his coinvestigators documented a procedural truism: The more cases an interventionalist performs, the better the results. However, even inexperienced users of the MitraClip were able to obtain at least moderate results – that is, residual grade 2 or less MR – 90% of the time or more.
“There is some change with greater experience, but it’s actually quite small,” according to Dr. Sorajja.
However, optimal results – grade 0 or 1 MR – are another matter entirely.
“For grade 1 or less, the learning curve is much steeper. It plateaus somewhere between 50 and 75 cases. In other words, in most cases you can get to moderate MR, but getting to grade 1 requires more experience. That relationship between case experience and outcome also applies to complication rates and case time,” he said.
Although at present the MitraClip is the only Food and Drug Administration–approved transcatheter device for MR repair, there are many others in the developmental pipeline, the he noted.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Achieving optimal surgical-like results via transcatheter repair of primary mitral regurgitation using the MitraClip in prohibitively high-surgical-risk patients becomes much more likely by taking into account key predictive anatomic and procedural features as well as the major comorbidities influencing outcome, Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
. Dr. Sorajja was first author of a study of 1-year outcomes in 2,952 patients with MR in the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry (STS/ACC TVT) who were commercially treated with the MitraClip, at present the only transcatheter device approved for this indication. Sixty-two percent had a surgical-like result, and their 1-year mortality rate of 21.7% was significantly lower than the 29.2% rate for patients with residual grade 2 MR and the 48.9% mortality in patients left with grade 3 or 4 MR.
It’s noteworthy that even though the acute procedural success rate – defined as residual grade 2 or less MR – was impressively high at 91.8% in this group of nearly 3,000 patients, roughly one in five in the overall series was rehospitalized for heart failure within 1 year, and one in four was dead. So there remains considerable room for improvement in long-term outcomes of transcatheter repair of MR, said Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute.
Anatomic predictors of good short-term outcome
“There are specific anatomic criteria, but an easier way to think about whether your patient could get an optimal result is to remember the physical limits of this therapy. What I teach is 1-2-5-50: the MitraClip device is about 1 cm tall, about 2 cm wide, and you need about 5 mm of leaflet inside the clip to create coaptation for MR reduction. And if you do that, you will reduce the mitral valve area by about 50%, so you have to be very careful in patients with small valve areas because you can worsen mitral stenosis,” the cardiologist explained.
Only two transechocardiographic views are needed to know if a patient will have a good result with the MitraClip. A bicommissural view traversing the valve medial to lateral shows where the MR jet is; if it’s in the middle of the mitral valve, that’s favorable because it means the interventionalist has a lot of freedom to operate. Then, going orthogonal from the bicommissural view to get an anterior-posterior view allows the operator to get a good look at the valve leaflets and apply the 1-2-5 rule to determine if the leaflet approximation is favorable, he continued.
Some mitral valve anatomy variants make it challenging to get surgical-like results with a transcatheter repair. These include calcified leaflets, large gaps between leaflets, Barlow’s valves, and small leaflets. Be aware of key success-limiting comorbidities.
In the STS/ACC TVT registry study, severe tricuspid regurgitation, present in 10% of patients preprocedurally, virtually doubled the adjusted risk of 1-year mortality in multivariate analyses.
“Tricuspid regurgitation is one of the most common concomitant lesions. And the presence of tricuspid regurgitation is ominous,” Dr. Sorajja said. “Treatment of concomitant lesions such as this is going to be necessary for us to get a truly surgical-like result in outcomes.”
Toward this end, he put in a plug to consider referring patients with severe tricuspid regurgitation for enrollment in the TRILUMINATE II trial, the pivotal U.S. trial for the investigational Tri-Clip device for transcatheter tricuspid valve repair, for which he is coprincipal investigator. The trial, pitting the Tri-Clip against medical therapy, is due to start in the spring of 2019.
In multivariate analyses of the MitraClip registry study, other predictors of the combined endpoint of death and rehospitalization for heart failure at 1 year, in addition to severe tricuspid regurgitation, included dialysis, with an adjusted 2.09-fold increased risk; moderate or severe lung disease, with a 1.28-fold risk; postprocedural residual MR; diminished left ventricular ejection fraction; and advanced age (J Am Coll Cardiol. 2017 Nov 7;70[19]:2315-27).
Case experience counts
In a soon-to-be-published more up-to-date analysis of more than 12,000 MitraClip patients in the STS/ACC TVT registry, which captures all U.S. commercial use of the device for its approved indication, Dr. Sorajja and his coinvestigators documented a procedural truism: The more cases an interventionalist performs, the better the results. However, even inexperienced users of the MitraClip were able to obtain at least moderate results – that is, residual grade 2 or less MR – 90% of the time or more.
“There is some change with greater experience, but it’s actually quite small,” according to Dr. Sorajja.
However, optimal results – grade 0 or 1 MR – are another matter entirely.
“For grade 1 or less, the learning curve is much steeper. It plateaus somewhere between 50 and 75 cases. In other words, in most cases you can get to moderate MR, but getting to grade 1 requires more experience. That relationship between case experience and outcome also applies to complication rates and case time,” he said.
Although at present the MitraClip is the only Food and Drug Administration–approved transcatheter device for MR repair, there are many others in the developmental pipeline, the he noted.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
SGLT2 inhibitors morph into HF drugs
SNOWMASS, COLO. – The oral sodium-glucose cotransporter-2 (SGLT2) inhibitors are the focus of a slew of ongoing phase 3 clinical trials in patients with symptomatic heart failure but no diabetes.
“We have a wide array of exciting opportunities to modify cardiovascular risk with agents that were initially developed for the therapy of diabetes. I think we’re increasingly moving to an age where these agents are actually cardiovascular drugs that happen to lower blood glucose, rather than the other way around, which is how they were initially conceived,” Akshay S. Desai, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
These are each multi-thousand-patient trials, variously due to be completed in 2019-2021. Of note, several of them are restricted to nondiabetic patients with heart failure with preserved ejection fraction (HFpEF), a common, serious, understudied, extremely high-cost disease sorely in need of effective pharmacotherapies, added Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital and a cardiologist at Harvard Medical School, Boston.
All of these placebo-controlled trials have as their composite primary endpoint cardiovascular death and heart failure hospitalization.
EMPEROR-Preserved has randomized 4,126 patients with HFpEF to empagliflozin (Jardiance) or placebo, while EMPEROR-Reduced involves 2,850 patients with heart failure with reduced ejection fraction (HFrEF). Both are due to be completed in 2020.
In addition, the DELIVER trial is focused on 4,700 HFpEF patients randomized to dapagliflozin (Farxiga) or placebo, while Dapa-HF employs the SGLT2 inhibitor in a study of 4,500 patients with HFrEF. Dapa-HF will be completed by late 2019. DELIVER wraps up in mid-2021.
Again, remarkably, none of the participants in these trials has diabetes. All have symptomatic heart failure with elevated N-terminal pro b-type natriuretic peptide levels. The impetus for this ongoing round of studies was the impressive reduction in the risk of hospitalization for heart failure seen in the pivotal trials that earned the SGLT2 inhibitors empagliflozin, canagliflozin (Invokana), and dapagliflozin marketing approval for treatment of type 2 diabetes from the Food and Drug Administration.
Dr. Desai called attention to a new systematic review and meta-analysis of cardiovascular outcomes in randomized, placebo-controlled trials of SGLT2 inhibitors in more than 34,000 patients with type 2 diabetes. The conclusion: These drugs impressively reduced the risk of heart failure hospitalization by 32% in patients with a baseline history of heart failure and similarly by 29% in those with no such history. Also notable was the 45% reduction in the risk of progression of renal disease regardless of whether patients had atherosclerotic cardiovascular disease (Lancet. 2019 Jan 5;393[10166]:31-9).
Only one of the ongoing round of phase 3 trials of SGLT2 inhibitors in heart failure is being conducted in patients with comorbid type 2 diabetes: the 4,000-subject SOLOIST-WHF trial. This study features the investigational dual inhibitor of SGLT1 and 2, sotagliflozin, with a primary outcome of cardiovascular death or heart failure hospitalization. Results are expected in early 2021.
What the latest guidelines say
The 2018 American Diabetes Association/European Association for the Study of Diabetes joint consensus statement on management of hyperglycemia in type 2 diabetes reflects an appreciation of the cardiovascular benefits of the SGLT2 inhibitors as well as the injectable glucagon-like peptide-1 receptor (GLP-1) agonists, which have shown significant reductions in major adverse cardiovascular events in pivotal trials including LEADER, HARMONY, and REWIND, albeit without the impressive reduction in heart failure hospitalizations documented with the SGLT2 inhibitors.
The consensus statement emphasizes that aggressive lifestyle modification advice is step No. 1, with the first-line medication being metformin titrated to a target of 1,000 mg twice daily. For patients with clinical heart failure or chronic kidney disease and atherosclerotic cardiovascular heart disease, the next drug recommended is an SGLT2 inhibitor with proven cardiovascular benefit. A GLP-1 agonist is recommended as the first injectable medication, ahead of insulin.
Who will take the lead in this new treatment strategy?
Dr. Desai presented data showing that overall utilization of SGLT2 inhibitors and GLP-1 agonists is going up, but not as steeply as it should.
“Cardiologists need to take a more active role,” he declared.
“It’s increasingly clear that, if we’re interested in modifying cardiovascular outcomes, we need to take ownership of this problem, much as we’ve done for lipids and hypertension, because modulating cardiovascular risk is our job,” Dr. Desai asserted. “These drugs may have modest influence on glycemic control, but the primary goal with these agents is to influence cardiovascular outcomes – and if we leave that job to our colleagues, then it often is just a can that gets kicked down the road.”
As a practical matter in prescribing SGLT2 inhibitors and GLP-1 agonists, he emphasized the value of partnering with a primary care physician, endocrinologist, and/or pharmacist by creating pathways for accelerated referral for pharmacologic teaching and, in the case of GLP-1 agonists, injection-related instruction. Pharmacists are often particularly helpful in obtaining prior authorization and financial approval for these medications, and they are familiar with drug discounts and vouchers.
“A great way to jump start collaboration is to provide the patient with a prescription before leaving your office. I think often what we do is just suggest it to the patient, and then a year later they come back and nothing has changed,” the cardiologist said.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
SNOWMASS, COLO. – The oral sodium-glucose cotransporter-2 (SGLT2) inhibitors are the focus of a slew of ongoing phase 3 clinical trials in patients with symptomatic heart failure but no diabetes.
“We have a wide array of exciting opportunities to modify cardiovascular risk with agents that were initially developed for the therapy of diabetes. I think we’re increasingly moving to an age where these agents are actually cardiovascular drugs that happen to lower blood glucose, rather than the other way around, which is how they were initially conceived,” Akshay S. Desai, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
These are each multi-thousand-patient trials, variously due to be completed in 2019-2021. Of note, several of them are restricted to nondiabetic patients with heart failure with preserved ejection fraction (HFpEF), a common, serious, understudied, extremely high-cost disease sorely in need of effective pharmacotherapies, added Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital and a cardiologist at Harvard Medical School, Boston.
All of these placebo-controlled trials have as their composite primary endpoint cardiovascular death and heart failure hospitalization.
EMPEROR-Preserved has randomized 4,126 patients with HFpEF to empagliflozin (Jardiance) or placebo, while EMPEROR-Reduced involves 2,850 patients with heart failure with reduced ejection fraction (HFrEF). Both are due to be completed in 2020.
In addition, the DELIVER trial is focused on 4,700 HFpEF patients randomized to dapagliflozin (Farxiga) or placebo, while Dapa-HF employs the SGLT2 inhibitor in a study of 4,500 patients with HFrEF. Dapa-HF will be completed by late 2019. DELIVER wraps up in mid-2021.
Again, remarkably, none of the participants in these trials has diabetes. All have symptomatic heart failure with elevated N-terminal pro b-type natriuretic peptide levels. The impetus for this ongoing round of studies was the impressive reduction in the risk of hospitalization for heart failure seen in the pivotal trials that earned the SGLT2 inhibitors empagliflozin, canagliflozin (Invokana), and dapagliflozin marketing approval for treatment of type 2 diabetes from the Food and Drug Administration.
Dr. Desai called attention to a new systematic review and meta-analysis of cardiovascular outcomes in randomized, placebo-controlled trials of SGLT2 inhibitors in more than 34,000 patients with type 2 diabetes. The conclusion: These drugs impressively reduced the risk of heart failure hospitalization by 32% in patients with a baseline history of heart failure and similarly by 29% in those with no such history. Also notable was the 45% reduction in the risk of progression of renal disease regardless of whether patients had atherosclerotic cardiovascular disease (Lancet. 2019 Jan 5;393[10166]:31-9).
Only one of the ongoing round of phase 3 trials of SGLT2 inhibitors in heart failure is being conducted in patients with comorbid type 2 diabetes: the 4,000-subject SOLOIST-WHF trial. This study features the investigational dual inhibitor of SGLT1 and 2, sotagliflozin, with a primary outcome of cardiovascular death or heart failure hospitalization. Results are expected in early 2021.
What the latest guidelines say
The 2018 American Diabetes Association/European Association for the Study of Diabetes joint consensus statement on management of hyperglycemia in type 2 diabetes reflects an appreciation of the cardiovascular benefits of the SGLT2 inhibitors as well as the injectable glucagon-like peptide-1 receptor (GLP-1) agonists, which have shown significant reductions in major adverse cardiovascular events in pivotal trials including LEADER, HARMONY, and REWIND, albeit without the impressive reduction in heart failure hospitalizations documented with the SGLT2 inhibitors.
The consensus statement emphasizes that aggressive lifestyle modification advice is step No. 1, with the first-line medication being metformin titrated to a target of 1,000 mg twice daily. For patients with clinical heart failure or chronic kidney disease and atherosclerotic cardiovascular heart disease, the next drug recommended is an SGLT2 inhibitor with proven cardiovascular benefit. A GLP-1 agonist is recommended as the first injectable medication, ahead of insulin.
Who will take the lead in this new treatment strategy?
Dr. Desai presented data showing that overall utilization of SGLT2 inhibitors and GLP-1 agonists is going up, but not as steeply as it should.
“Cardiologists need to take a more active role,” he declared.
“It’s increasingly clear that, if we’re interested in modifying cardiovascular outcomes, we need to take ownership of this problem, much as we’ve done for lipids and hypertension, because modulating cardiovascular risk is our job,” Dr. Desai asserted. “These drugs may have modest influence on glycemic control, but the primary goal with these agents is to influence cardiovascular outcomes – and if we leave that job to our colleagues, then it often is just a can that gets kicked down the road.”
As a practical matter in prescribing SGLT2 inhibitors and GLP-1 agonists, he emphasized the value of partnering with a primary care physician, endocrinologist, and/or pharmacist by creating pathways for accelerated referral for pharmacologic teaching and, in the case of GLP-1 agonists, injection-related instruction. Pharmacists are often particularly helpful in obtaining prior authorization and financial approval for these medications, and they are familiar with drug discounts and vouchers.
“A great way to jump start collaboration is to provide the patient with a prescription before leaving your office. I think often what we do is just suggest it to the patient, and then a year later they come back and nothing has changed,” the cardiologist said.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
SNOWMASS, COLO. – The oral sodium-glucose cotransporter-2 (SGLT2) inhibitors are the focus of a slew of ongoing phase 3 clinical trials in patients with symptomatic heart failure but no diabetes.
“We have a wide array of exciting opportunities to modify cardiovascular risk with agents that were initially developed for the therapy of diabetes. I think we’re increasingly moving to an age where these agents are actually cardiovascular drugs that happen to lower blood glucose, rather than the other way around, which is how they were initially conceived,” Akshay S. Desai, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
These are each multi-thousand-patient trials, variously due to be completed in 2019-2021. Of note, several of them are restricted to nondiabetic patients with heart failure with preserved ejection fraction (HFpEF), a common, serious, understudied, extremely high-cost disease sorely in need of effective pharmacotherapies, added Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital and a cardiologist at Harvard Medical School, Boston.
All of these placebo-controlled trials have as their composite primary endpoint cardiovascular death and heart failure hospitalization.
EMPEROR-Preserved has randomized 4,126 patients with HFpEF to empagliflozin (Jardiance) or placebo, while EMPEROR-Reduced involves 2,850 patients with heart failure with reduced ejection fraction (HFrEF). Both are due to be completed in 2020.
In addition, the DELIVER trial is focused on 4,700 HFpEF patients randomized to dapagliflozin (Farxiga) or placebo, while Dapa-HF employs the SGLT2 inhibitor in a study of 4,500 patients with HFrEF. Dapa-HF will be completed by late 2019. DELIVER wraps up in mid-2021.
Again, remarkably, none of the participants in these trials has diabetes. All have symptomatic heart failure with elevated N-terminal pro b-type natriuretic peptide levels. The impetus for this ongoing round of studies was the impressive reduction in the risk of hospitalization for heart failure seen in the pivotal trials that earned the SGLT2 inhibitors empagliflozin, canagliflozin (Invokana), and dapagliflozin marketing approval for treatment of type 2 diabetes from the Food and Drug Administration.
Dr. Desai called attention to a new systematic review and meta-analysis of cardiovascular outcomes in randomized, placebo-controlled trials of SGLT2 inhibitors in more than 34,000 patients with type 2 diabetes. The conclusion: These drugs impressively reduced the risk of heart failure hospitalization by 32% in patients with a baseline history of heart failure and similarly by 29% in those with no such history. Also notable was the 45% reduction in the risk of progression of renal disease regardless of whether patients had atherosclerotic cardiovascular disease (Lancet. 2019 Jan 5;393[10166]:31-9).
Only one of the ongoing round of phase 3 trials of SGLT2 inhibitors in heart failure is being conducted in patients with comorbid type 2 diabetes: the 4,000-subject SOLOIST-WHF trial. This study features the investigational dual inhibitor of SGLT1 and 2, sotagliflozin, with a primary outcome of cardiovascular death or heart failure hospitalization. Results are expected in early 2021.
What the latest guidelines say
The 2018 American Diabetes Association/European Association for the Study of Diabetes joint consensus statement on management of hyperglycemia in type 2 diabetes reflects an appreciation of the cardiovascular benefits of the SGLT2 inhibitors as well as the injectable glucagon-like peptide-1 receptor (GLP-1) agonists, which have shown significant reductions in major adverse cardiovascular events in pivotal trials including LEADER, HARMONY, and REWIND, albeit without the impressive reduction in heart failure hospitalizations documented with the SGLT2 inhibitors.
The consensus statement emphasizes that aggressive lifestyle modification advice is step No. 1, with the first-line medication being metformin titrated to a target of 1,000 mg twice daily. For patients with clinical heart failure or chronic kidney disease and atherosclerotic cardiovascular heart disease, the next drug recommended is an SGLT2 inhibitor with proven cardiovascular benefit. A GLP-1 agonist is recommended as the first injectable medication, ahead of insulin.
Who will take the lead in this new treatment strategy?
Dr. Desai presented data showing that overall utilization of SGLT2 inhibitors and GLP-1 agonists is going up, but not as steeply as it should.
“Cardiologists need to take a more active role,” he declared.
“It’s increasingly clear that, if we’re interested in modifying cardiovascular outcomes, we need to take ownership of this problem, much as we’ve done for lipids and hypertension, because modulating cardiovascular risk is our job,” Dr. Desai asserted. “These drugs may have modest influence on glycemic control, but the primary goal with these agents is to influence cardiovascular outcomes – and if we leave that job to our colleagues, then it often is just a can that gets kicked down the road.”
As a practical matter in prescribing SGLT2 inhibitors and GLP-1 agonists, he emphasized the value of partnering with a primary care physician, endocrinologist, and/or pharmacist by creating pathways for accelerated referral for pharmacologic teaching and, in the case of GLP-1 agonists, injection-related instruction. Pharmacists are often particularly helpful in obtaining prior authorization and financial approval for these medications, and they are familiar with drug discounts and vouchers.
“A great way to jump start collaboration is to provide the patient with a prescription before leaving your office. I think often what we do is just suggest it to the patient, and then a year later they come back and nothing has changed,” the cardiologist said.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Moment of truth approaches for low-risk TAVR
SNOWMASS, COLO. – There are now more transcatheter aortic valve replacements performed each year than surgical ones in the United States, a disparity that may grow vastly larger.
That’s if the results of the two pivotal randomized trials comparing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in low-surgical-risk patients scheduled for presentation at the annual scientific session of the American College of Cardiology in March turn out to show TAVR outcomes are equivalent or superior to SAVR.
And that just might be the scenario, provided the eye-popping results already reported from another, much smaller study – the Low Risk TAVR study, a 200-patient, prospective, nonrandomized, observational study – are at all reflective of what’s to come when the pivotal PARTNER 3 and EVOLUT R trials are released at the ACC meeting in New Orleans, Michael J. Mack, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“The TAVR train has left the station on the way to low risk, and I don’t really see it coming back,” said Dr. Mack, medical director for cardiothoracic surgery at Baylor Scott & White Health in Dallas.
He wasn’t part of the Low Risk TAVR study, in which 200 low-surgical-risk patients with symptomatic severe aortic stenosis underwent TAVR with contemporary devices at 11 centers and were matched to 719 historical control SAVR patients at the same centers. But he called the study results “pretty spectacular”: zero 30-day all cause mortality in the TAVR group versus 1.7% with SAVR, no in-hospital strokes with TAVR versus a 0.6% rate with SAVR, and similar permanent pacemaker implantation rates of 5.0% with TAVR and 4.5% with SAVR.
Also, the TAVR group had a mere 3.0% rate of new-onset atrial fibrillation, a 2-day hospital length of stay, and a 0.5% incidence of greater-than-mild paravalvular leak at 30 days (J Am Coll Cardiol. 2018 Oct 30;72[18]:2095-105).
The two major trials due to report 1-year outcomes at the ACC meeting in March are similarly designed. The PARTNER 3 trial includes 1,000 low-surgical-risk patients with a mean age of 73 years and a predicted 30-day surgical mortality risk of 1.9%. Seventy-one percent of them were New York Heart Association (NYHA) Class II at enrollment. Participants were randomized to TAVR with the Edwards Lifesciences Sapien 3 valve or to SAVR, with the primary outcome being a composite of all-cause mortality, stroke, and rehospitalization 1 year post procedure. The EVOLUT R trial is similar, except the TAVR valve is the Medtronic CoreValve.
Both trials will continue to follow patients annually for 10 years in order to address the still-open issue of TAVR and SAVR valve durability. Also, the Food and Drug Administration has mandated that 4D CT imaging substudies be conducted in 800 of the combined 2,000 participants in the two trials in order to provide new insight into the issue of subclinical valve leaflet thrombosis, which was detected in 14% of participants in the Low Risk TAVR study 30 days post procedure.
“The clinical impact and need for anticoagulant therapy are currently unknown. However, clot anywhere else in the body doesn’t do good things, so it’s hard to imagine it’s helping here. Pretending it doesn’t exist isn’t going to make the problem go away,” Dr. Mack said.
The 4D CT imaging substudy results are expected to be presented later this year at the Transcatheter Cardiovascular Therapeutics conference in San Francisco.
In 2017, 51,064 TAVR procedures for symptomatic severe aortic stenosis were done in the United States, compared with 41,490 SAVRs. The past several years have seen a decreasing proportion of TAVRs being done in high-surgical-risk patients and a growing proportion in intermediate-risk patients.
Even if PARTNER 3 and EVOLUT R prove to be resoundingly positive for TAVR in low-risk patients, however, SAVR is not going to vanish, according to Dr. Mack. He cited four factors working against universal adoption of TAVR: the uncertainty surrounding valve durability, which will take years to resolve; the issue of TAVR valve leaflet thrombosis and the for-now theoretic possibility that all TAVR patients might need to receive postprocedure oral anticoagulation; the high rate of new permanent pacemaker implantation associated with TAVR, which Dr. Mack called the procedure’s Achilles heel; and the total absence of high-quality data on TAVR in patients with bicuspid aortic stenosis.
Even though TAVR for diseased bicuspid valves is not off-label therapy – the FDA’s indication for TAVR is for native valve aortic stenosis – patients with bicuspid valves weren’t included in any of the randomized trials, he explained.
Younger patients are likely to stick with SAVR for the foreseeable future, regardless of the outcomes of PARTNER 3 and EVOLUT R, according to the surgeon, because of the unresolved issue of valve durability, as well as TAVR’s greater associated need for a permanent pacemaker, both significant considerations in individuals with a life expectancy of another 20-30 years.
There are now roughly 600 TAVR centers and 1,150 SAVR centers nationally. One of the hot topics in the field stems from the fact that half of these TAVR centers do only one TAVR per week or less. That’s concerning in light of a recent New York State study showing a clear association between operator volume and outcomes.
“The more you do, the better your outcomes are, similar to many other procedures in medicine,” Dr. Mack commented.
On the other hand, it’s unlikely that patients who present to one of the roughly 550 SAVR-only centers are truly getting informed consent as to their options, he added.
TAVR timeline for 2019
March
PARTNER 3 and EVOLUT R primary outcomes to be presented at the American College of Cardiology annual scientific session.
Centers for Medicare & Medicaid Services to issue proposal for a revised National Coverage Determination for TAVR reimbursement.
June
Following a public comment period, CMS will release final revised criteria for TAVR reimbursement.
September
Results of the PARTNER 3 and EVOLUT R 4D CT imaging substudies will probably be presented late in the month at the annual Transcatheter Cardiovascular Therapeutics conference in San Francisco.
Late 2019
If PARTNER 3 and EVOLUT R trials are positive, FDA approval of the TAVR valves in low-surgical-risk patients is expected.
Dr. Mack is coprincipal investigator of PARTNER 3, which was sponsored by Edwards Lifesciences, and of Abbott Vascular’s COAPT trial. He’s also on the executive committee of the INTREPID trial, sponsored by Medtronic.
SNOWMASS, COLO. – There are now more transcatheter aortic valve replacements performed each year than surgical ones in the United States, a disparity that may grow vastly larger.
That’s if the results of the two pivotal randomized trials comparing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in low-surgical-risk patients scheduled for presentation at the annual scientific session of the American College of Cardiology in March turn out to show TAVR outcomes are equivalent or superior to SAVR.
And that just might be the scenario, provided the eye-popping results already reported from another, much smaller study – the Low Risk TAVR study, a 200-patient, prospective, nonrandomized, observational study – are at all reflective of what’s to come when the pivotal PARTNER 3 and EVOLUT R trials are released at the ACC meeting in New Orleans, Michael J. Mack, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“The TAVR train has left the station on the way to low risk, and I don’t really see it coming back,” said Dr. Mack, medical director for cardiothoracic surgery at Baylor Scott & White Health in Dallas.
He wasn’t part of the Low Risk TAVR study, in which 200 low-surgical-risk patients with symptomatic severe aortic stenosis underwent TAVR with contemporary devices at 11 centers and were matched to 719 historical control SAVR patients at the same centers. But he called the study results “pretty spectacular”: zero 30-day all cause mortality in the TAVR group versus 1.7% with SAVR, no in-hospital strokes with TAVR versus a 0.6% rate with SAVR, and similar permanent pacemaker implantation rates of 5.0% with TAVR and 4.5% with SAVR.
Also, the TAVR group had a mere 3.0% rate of new-onset atrial fibrillation, a 2-day hospital length of stay, and a 0.5% incidence of greater-than-mild paravalvular leak at 30 days (J Am Coll Cardiol. 2018 Oct 30;72[18]:2095-105).
The two major trials due to report 1-year outcomes at the ACC meeting in March are similarly designed. The PARTNER 3 trial includes 1,000 low-surgical-risk patients with a mean age of 73 years and a predicted 30-day surgical mortality risk of 1.9%. Seventy-one percent of them were New York Heart Association (NYHA) Class II at enrollment. Participants were randomized to TAVR with the Edwards Lifesciences Sapien 3 valve or to SAVR, with the primary outcome being a composite of all-cause mortality, stroke, and rehospitalization 1 year post procedure. The EVOLUT R trial is similar, except the TAVR valve is the Medtronic CoreValve.
Both trials will continue to follow patients annually for 10 years in order to address the still-open issue of TAVR and SAVR valve durability. Also, the Food and Drug Administration has mandated that 4D CT imaging substudies be conducted in 800 of the combined 2,000 participants in the two trials in order to provide new insight into the issue of subclinical valve leaflet thrombosis, which was detected in 14% of participants in the Low Risk TAVR study 30 days post procedure.
“The clinical impact and need for anticoagulant therapy are currently unknown. However, clot anywhere else in the body doesn’t do good things, so it’s hard to imagine it’s helping here. Pretending it doesn’t exist isn’t going to make the problem go away,” Dr. Mack said.
The 4D CT imaging substudy results are expected to be presented later this year at the Transcatheter Cardiovascular Therapeutics conference in San Francisco.
In 2017, 51,064 TAVR procedures for symptomatic severe aortic stenosis were done in the United States, compared with 41,490 SAVRs. The past several years have seen a decreasing proportion of TAVRs being done in high-surgical-risk patients and a growing proportion in intermediate-risk patients.
Even if PARTNER 3 and EVOLUT R prove to be resoundingly positive for TAVR in low-risk patients, however, SAVR is not going to vanish, according to Dr. Mack. He cited four factors working against universal adoption of TAVR: the uncertainty surrounding valve durability, which will take years to resolve; the issue of TAVR valve leaflet thrombosis and the for-now theoretic possibility that all TAVR patients might need to receive postprocedure oral anticoagulation; the high rate of new permanent pacemaker implantation associated with TAVR, which Dr. Mack called the procedure’s Achilles heel; and the total absence of high-quality data on TAVR in patients with bicuspid aortic stenosis.
Even though TAVR for diseased bicuspid valves is not off-label therapy – the FDA’s indication for TAVR is for native valve aortic stenosis – patients with bicuspid valves weren’t included in any of the randomized trials, he explained.
Younger patients are likely to stick with SAVR for the foreseeable future, regardless of the outcomes of PARTNER 3 and EVOLUT R, according to the surgeon, because of the unresolved issue of valve durability, as well as TAVR’s greater associated need for a permanent pacemaker, both significant considerations in individuals with a life expectancy of another 20-30 years.
There are now roughly 600 TAVR centers and 1,150 SAVR centers nationally. One of the hot topics in the field stems from the fact that half of these TAVR centers do only one TAVR per week or less. That’s concerning in light of a recent New York State study showing a clear association between operator volume and outcomes.
“The more you do, the better your outcomes are, similar to many other procedures in medicine,” Dr. Mack commented.
On the other hand, it’s unlikely that patients who present to one of the roughly 550 SAVR-only centers are truly getting informed consent as to their options, he added.
TAVR timeline for 2019
March
PARTNER 3 and EVOLUT R primary outcomes to be presented at the American College of Cardiology annual scientific session.
Centers for Medicare & Medicaid Services to issue proposal for a revised National Coverage Determination for TAVR reimbursement.
June
Following a public comment period, CMS will release final revised criteria for TAVR reimbursement.
September
Results of the PARTNER 3 and EVOLUT R 4D CT imaging substudies will probably be presented late in the month at the annual Transcatheter Cardiovascular Therapeutics conference in San Francisco.
Late 2019
If PARTNER 3 and EVOLUT R trials are positive, FDA approval of the TAVR valves in low-surgical-risk patients is expected.
Dr. Mack is coprincipal investigator of PARTNER 3, which was sponsored by Edwards Lifesciences, and of Abbott Vascular’s COAPT trial. He’s also on the executive committee of the INTREPID trial, sponsored by Medtronic.
SNOWMASS, COLO. – There are now more transcatheter aortic valve replacements performed each year than surgical ones in the United States, a disparity that may grow vastly larger.
That’s if the results of the two pivotal randomized trials comparing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in low-surgical-risk patients scheduled for presentation at the annual scientific session of the American College of Cardiology in March turn out to show TAVR outcomes are equivalent or superior to SAVR.
And that just might be the scenario, provided the eye-popping results already reported from another, much smaller study – the Low Risk TAVR study, a 200-patient, prospective, nonrandomized, observational study – are at all reflective of what’s to come when the pivotal PARTNER 3 and EVOLUT R trials are released at the ACC meeting in New Orleans, Michael J. Mack, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“The TAVR train has left the station on the way to low risk, and I don’t really see it coming back,” said Dr. Mack, medical director for cardiothoracic surgery at Baylor Scott & White Health in Dallas.
He wasn’t part of the Low Risk TAVR study, in which 200 low-surgical-risk patients with symptomatic severe aortic stenosis underwent TAVR with contemporary devices at 11 centers and were matched to 719 historical control SAVR patients at the same centers. But he called the study results “pretty spectacular”: zero 30-day all cause mortality in the TAVR group versus 1.7% with SAVR, no in-hospital strokes with TAVR versus a 0.6% rate with SAVR, and similar permanent pacemaker implantation rates of 5.0% with TAVR and 4.5% with SAVR.
Also, the TAVR group had a mere 3.0% rate of new-onset atrial fibrillation, a 2-day hospital length of stay, and a 0.5% incidence of greater-than-mild paravalvular leak at 30 days (J Am Coll Cardiol. 2018 Oct 30;72[18]:2095-105).
The two major trials due to report 1-year outcomes at the ACC meeting in March are similarly designed. The PARTNER 3 trial includes 1,000 low-surgical-risk patients with a mean age of 73 years and a predicted 30-day surgical mortality risk of 1.9%. Seventy-one percent of them were New York Heart Association (NYHA) Class II at enrollment. Participants were randomized to TAVR with the Edwards Lifesciences Sapien 3 valve or to SAVR, with the primary outcome being a composite of all-cause mortality, stroke, and rehospitalization 1 year post procedure. The EVOLUT R trial is similar, except the TAVR valve is the Medtronic CoreValve.
Both trials will continue to follow patients annually for 10 years in order to address the still-open issue of TAVR and SAVR valve durability. Also, the Food and Drug Administration has mandated that 4D CT imaging substudies be conducted in 800 of the combined 2,000 participants in the two trials in order to provide new insight into the issue of subclinical valve leaflet thrombosis, which was detected in 14% of participants in the Low Risk TAVR study 30 days post procedure.
“The clinical impact and need for anticoagulant therapy are currently unknown. However, clot anywhere else in the body doesn’t do good things, so it’s hard to imagine it’s helping here. Pretending it doesn’t exist isn’t going to make the problem go away,” Dr. Mack said.
The 4D CT imaging substudy results are expected to be presented later this year at the Transcatheter Cardiovascular Therapeutics conference in San Francisco.
In 2017, 51,064 TAVR procedures for symptomatic severe aortic stenosis were done in the United States, compared with 41,490 SAVRs. The past several years have seen a decreasing proportion of TAVRs being done in high-surgical-risk patients and a growing proportion in intermediate-risk patients.
Even if PARTNER 3 and EVOLUT R prove to be resoundingly positive for TAVR in low-risk patients, however, SAVR is not going to vanish, according to Dr. Mack. He cited four factors working against universal adoption of TAVR: the uncertainty surrounding valve durability, which will take years to resolve; the issue of TAVR valve leaflet thrombosis and the for-now theoretic possibility that all TAVR patients might need to receive postprocedure oral anticoagulation; the high rate of new permanent pacemaker implantation associated with TAVR, which Dr. Mack called the procedure’s Achilles heel; and the total absence of high-quality data on TAVR in patients with bicuspid aortic stenosis.
Even though TAVR for diseased bicuspid valves is not off-label therapy – the FDA’s indication for TAVR is for native valve aortic stenosis – patients with bicuspid valves weren’t included in any of the randomized trials, he explained.
Younger patients are likely to stick with SAVR for the foreseeable future, regardless of the outcomes of PARTNER 3 and EVOLUT R, according to the surgeon, because of the unresolved issue of valve durability, as well as TAVR’s greater associated need for a permanent pacemaker, both significant considerations in individuals with a life expectancy of another 20-30 years.
There are now roughly 600 TAVR centers and 1,150 SAVR centers nationally. One of the hot topics in the field stems from the fact that half of these TAVR centers do only one TAVR per week or less. That’s concerning in light of a recent New York State study showing a clear association between operator volume and outcomes.
“The more you do, the better your outcomes are, similar to many other procedures in medicine,” Dr. Mack commented.
On the other hand, it’s unlikely that patients who present to one of the roughly 550 SAVR-only centers are truly getting informed consent as to their options, he added.
TAVR timeline for 2019
March
PARTNER 3 and EVOLUT R primary outcomes to be presented at the American College of Cardiology annual scientific session.
Centers for Medicare & Medicaid Services to issue proposal for a revised National Coverage Determination for TAVR reimbursement.
June
Following a public comment period, CMS will release final revised criteria for TAVR reimbursement.
September
Results of the PARTNER 3 and EVOLUT R 4D CT imaging substudies will probably be presented late in the month at the annual Transcatheter Cardiovascular Therapeutics conference in San Francisco.
Late 2019
If PARTNER 3 and EVOLUT R trials are positive, FDA approval of the TAVR valves in low-surgical-risk patients is expected.
Dr. Mack is coprincipal investigator of PARTNER 3, which was sponsored by Edwards Lifesciences, and of Abbott Vascular’s COAPT trial. He’s also on the executive committee of the INTREPID trial, sponsored by Medtronic.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Pregnancy problems predict cardiovascular future
SNOWMASS, COLO. – Think of pregnancy as a cardiovascular stress test, Carole A. Warnes, MD, urged at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Pregnancy complications may unmask a predisposition to premature cardiovascular disease. Yet a woman’s reproductive history is often overlooked in this regard, despite the fact that cardiovascular disease is the number-one cause of death in women, observed Dr. Warnes, the Snowmass conference director and professor of medicine at the Mayo Clinic in Rochester, Minn.
“I think reproductive history is often overlooked as a predictor of cardiovascular and even peripheral vascular events. I suspect many of us don’t routinely ask our patients about miscarriages and stillbirths. We might think about preeclampsia, but these are also hallmarks of trouble to come,” the cardiologist said.
Indeed, this point was underscored in a retrospective Danish national population-based cohort registry study of more than 1 million women followed for nearly 16 million person-years after one or more miscarriages, stillbirths, or live singleton births. Women with stillbirths were 2.69-fold more likely to have an MI, 2.42-fold more likely to develop renovascular hypertension, and 1.74-fold more likely to have a stroke during follow-up than those with no stillbirths.
Moreover, women with miscarriages were 1.13-, 1.2-, and 1.16-fold more likely to have an MI, renovascular hypertension, and stroke, respectively, than women with no miscarriages. And the risks were additive: For each additional miscarriage, the risks of MI, renovascular hypertension, and stroke increased by 9%, 19%, and 13%, respectively (Circulation. 2013;127[17]:1775-82).
The concept of maternal placental syndromes encompasses four events believed to originate from diseased placental blood vessels: preeclampsia, gestational hypertension, placental abruption, and placental infarction. In a population-based retrospective study known as CHAMPS (Cardiovascular Health After Maternal Placental Syndromes), conducted in more than 1 million Ontario women who were free from cardiovascular disease prior to their first delivery, 7% were diagnosed with a maternal placental syndrome. Their incidence of a composite endpoint comprised of hospitalization or revascularization for CAD, peripheral artery disease, or cerebrovascular disease at least 90 days after delivery discharge was double that of women without a maternal placental syndrome.
“These women manifested their first cardiovascular event at an average age of 38, not 50 or 60,” Dr. Warnes said.
The risk of premature cardiovascular disease was magnified 4.4-fold in women with a maternal placental syndrome plus an intrauterine fetal death, compared with those with neither, after adjustment for sociodemographic factors and other potential confounders, and by 3.1-fold in women with a maternal placental syndrome and poor fetal growth (Lancet. 2005;366[9499]:1797-803).
These findings were independently confirmed recently in a population-based retrospective study of nearly 303,000 Florida women free of prepregnancy hypertension, diabetes, heart disease, or renal disease who were followed for a median of 4.9 years after their first delivery. During that relative brief follow-up period, the adjusted risk of cardiovascular disease was increased by 19% in those with a maternal placental syndrome, compared with those without. And the risk was additive: women with more than one maternal placental syndrome had a 43% greater short-term risk of developing cardiovascular disease, compared with those with none. And when women with a maternal placental syndrome also had a preterm birth or a small-for-gestational age baby, their risk increased 45% (Am J Obstet Gynecol. 2016;215[4]:484.e1-484.e14).
It’s not just preeclampsia, which affects 3%-5% of all pregnancies, and gestational hypertension – defined as high blood pressure arising only after 20 weeks’ gestation and without proteinuria – that have been linked to future premature cardiovascular disease. In the Northern Finland Birth Cohort 1966, in which investigators have followed 10,314 women born in that year for 39 years, any form of high blood pressure during pregnancy was a harbinger of subsequent cardiovascular disease, diabetes, and chronic kidney disease. That included chronic isolated systolic and isolated diastolic hypertension (Circulation. 2013;127[6]:681-90).
The pathophysiologic processes involved in complicated pregnancies echo those of CAD and stroke: inflammation, altered angiogenesis, vasculopathy, thrombosis, and insulin resistance. Still unsettled, however, is the chicken-versus-egg question of whether preeclampsia and other pregnancy complications represent the initial expression of an adverse phenotype associated with early development of cardiovascular disease or the complications injure the vascular endothelium and thereby trigger accelerated atherosclerosis. In any case, markers of endothelial activation have been documented up to 15 years after an episode of preeclampsia, Dr. Warnes said.
All of these data underscore the importance of identifying at-risk women based upon reproductive history, scheduling additional medical checkups so they don’t drop off the radar for the next 20 years, encouraging lifestyle modification, and giving consideration to early initiation of antihypertensive and lipid-lowering therapies.
“Pregnancy complications give us a glimpse of this awful disease trajectory at a time when women are completely asymptomatic and we could intervene and perhaps change outcomes with targeted therapy when it might be expected to work better and patients might be more receptive to such interventions,” she said.
Dr. Warnes reported having no financial conflicts of interest.
SNOWMASS, COLO. – Think of pregnancy as a cardiovascular stress test, Carole A. Warnes, MD, urged at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Pregnancy complications may unmask a predisposition to premature cardiovascular disease. Yet a woman’s reproductive history is often overlooked in this regard, despite the fact that cardiovascular disease is the number-one cause of death in women, observed Dr. Warnes, the Snowmass conference director and professor of medicine at the Mayo Clinic in Rochester, Minn.
“I think reproductive history is often overlooked as a predictor of cardiovascular and even peripheral vascular events. I suspect many of us don’t routinely ask our patients about miscarriages and stillbirths. We might think about preeclampsia, but these are also hallmarks of trouble to come,” the cardiologist said.
Indeed, this point was underscored in a retrospective Danish national population-based cohort registry study of more than 1 million women followed for nearly 16 million person-years after one or more miscarriages, stillbirths, or live singleton births. Women with stillbirths were 2.69-fold more likely to have an MI, 2.42-fold more likely to develop renovascular hypertension, and 1.74-fold more likely to have a stroke during follow-up than those with no stillbirths.
Moreover, women with miscarriages were 1.13-, 1.2-, and 1.16-fold more likely to have an MI, renovascular hypertension, and stroke, respectively, than women with no miscarriages. And the risks were additive: For each additional miscarriage, the risks of MI, renovascular hypertension, and stroke increased by 9%, 19%, and 13%, respectively (Circulation. 2013;127[17]:1775-82).
The concept of maternal placental syndromes encompasses four events believed to originate from diseased placental blood vessels: preeclampsia, gestational hypertension, placental abruption, and placental infarction. In a population-based retrospective study known as CHAMPS (Cardiovascular Health After Maternal Placental Syndromes), conducted in more than 1 million Ontario women who were free from cardiovascular disease prior to their first delivery, 7% were diagnosed with a maternal placental syndrome. Their incidence of a composite endpoint comprised of hospitalization or revascularization for CAD, peripheral artery disease, or cerebrovascular disease at least 90 days after delivery discharge was double that of women without a maternal placental syndrome.
“These women manifested their first cardiovascular event at an average age of 38, not 50 or 60,” Dr. Warnes said.
The risk of premature cardiovascular disease was magnified 4.4-fold in women with a maternal placental syndrome plus an intrauterine fetal death, compared with those with neither, after adjustment for sociodemographic factors and other potential confounders, and by 3.1-fold in women with a maternal placental syndrome and poor fetal growth (Lancet. 2005;366[9499]:1797-803).
These findings were independently confirmed recently in a population-based retrospective study of nearly 303,000 Florida women free of prepregnancy hypertension, diabetes, heart disease, or renal disease who were followed for a median of 4.9 years after their first delivery. During that relative brief follow-up period, the adjusted risk of cardiovascular disease was increased by 19% in those with a maternal placental syndrome, compared with those without. And the risk was additive: women with more than one maternal placental syndrome had a 43% greater short-term risk of developing cardiovascular disease, compared with those with none. And when women with a maternal placental syndrome also had a preterm birth or a small-for-gestational age baby, their risk increased 45% (Am J Obstet Gynecol. 2016;215[4]:484.e1-484.e14).
It’s not just preeclampsia, which affects 3%-5% of all pregnancies, and gestational hypertension – defined as high blood pressure arising only after 20 weeks’ gestation and without proteinuria – that have been linked to future premature cardiovascular disease. In the Northern Finland Birth Cohort 1966, in which investigators have followed 10,314 women born in that year for 39 years, any form of high blood pressure during pregnancy was a harbinger of subsequent cardiovascular disease, diabetes, and chronic kidney disease. That included chronic isolated systolic and isolated diastolic hypertension (Circulation. 2013;127[6]:681-90).
The pathophysiologic processes involved in complicated pregnancies echo those of CAD and stroke: inflammation, altered angiogenesis, vasculopathy, thrombosis, and insulin resistance. Still unsettled, however, is the chicken-versus-egg question of whether preeclampsia and other pregnancy complications represent the initial expression of an adverse phenotype associated with early development of cardiovascular disease or the complications injure the vascular endothelium and thereby trigger accelerated atherosclerosis. In any case, markers of endothelial activation have been documented up to 15 years after an episode of preeclampsia, Dr. Warnes said.
All of these data underscore the importance of identifying at-risk women based upon reproductive history, scheduling additional medical checkups so they don’t drop off the radar for the next 20 years, encouraging lifestyle modification, and giving consideration to early initiation of antihypertensive and lipid-lowering therapies.
“Pregnancy complications give us a glimpse of this awful disease trajectory at a time when women are completely asymptomatic and we could intervene and perhaps change outcomes with targeted therapy when it might be expected to work better and patients might be more receptive to such interventions,” she said.
Dr. Warnes reported having no financial conflicts of interest.
SNOWMASS, COLO. – Think of pregnancy as a cardiovascular stress test, Carole A. Warnes, MD, urged at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Pregnancy complications may unmask a predisposition to premature cardiovascular disease. Yet a woman’s reproductive history is often overlooked in this regard, despite the fact that cardiovascular disease is the number-one cause of death in women, observed Dr. Warnes, the Snowmass conference director and professor of medicine at the Mayo Clinic in Rochester, Minn.
“I think reproductive history is often overlooked as a predictor of cardiovascular and even peripheral vascular events. I suspect many of us don’t routinely ask our patients about miscarriages and stillbirths. We might think about preeclampsia, but these are also hallmarks of trouble to come,” the cardiologist said.
Indeed, this point was underscored in a retrospective Danish national population-based cohort registry study of more than 1 million women followed for nearly 16 million person-years after one or more miscarriages, stillbirths, or live singleton births. Women with stillbirths were 2.69-fold more likely to have an MI, 2.42-fold more likely to develop renovascular hypertension, and 1.74-fold more likely to have a stroke during follow-up than those with no stillbirths.
Moreover, women with miscarriages were 1.13-, 1.2-, and 1.16-fold more likely to have an MI, renovascular hypertension, and stroke, respectively, than women with no miscarriages. And the risks were additive: For each additional miscarriage, the risks of MI, renovascular hypertension, and stroke increased by 9%, 19%, and 13%, respectively (Circulation. 2013;127[17]:1775-82).
The concept of maternal placental syndromes encompasses four events believed to originate from diseased placental blood vessels: preeclampsia, gestational hypertension, placental abruption, and placental infarction. In a population-based retrospective study known as CHAMPS (Cardiovascular Health After Maternal Placental Syndromes), conducted in more than 1 million Ontario women who were free from cardiovascular disease prior to their first delivery, 7% were diagnosed with a maternal placental syndrome. Their incidence of a composite endpoint comprised of hospitalization or revascularization for CAD, peripheral artery disease, or cerebrovascular disease at least 90 days after delivery discharge was double that of women without a maternal placental syndrome.
“These women manifested their first cardiovascular event at an average age of 38, not 50 or 60,” Dr. Warnes said.
The risk of premature cardiovascular disease was magnified 4.4-fold in women with a maternal placental syndrome plus an intrauterine fetal death, compared with those with neither, after adjustment for sociodemographic factors and other potential confounders, and by 3.1-fold in women with a maternal placental syndrome and poor fetal growth (Lancet. 2005;366[9499]:1797-803).
These findings were independently confirmed recently in a population-based retrospective study of nearly 303,000 Florida women free of prepregnancy hypertension, diabetes, heart disease, or renal disease who were followed for a median of 4.9 years after their first delivery. During that relative brief follow-up period, the adjusted risk of cardiovascular disease was increased by 19% in those with a maternal placental syndrome, compared with those without. And the risk was additive: women with more than one maternal placental syndrome had a 43% greater short-term risk of developing cardiovascular disease, compared with those with none. And when women with a maternal placental syndrome also had a preterm birth or a small-for-gestational age baby, their risk increased 45% (Am J Obstet Gynecol. 2016;215[4]:484.e1-484.e14).
It’s not just preeclampsia, which affects 3%-5% of all pregnancies, and gestational hypertension – defined as high blood pressure arising only after 20 weeks’ gestation and without proteinuria – that have been linked to future premature cardiovascular disease. In the Northern Finland Birth Cohort 1966, in which investigators have followed 10,314 women born in that year for 39 years, any form of high blood pressure during pregnancy was a harbinger of subsequent cardiovascular disease, diabetes, and chronic kidney disease. That included chronic isolated systolic and isolated diastolic hypertension (Circulation. 2013;127[6]:681-90).
The pathophysiologic processes involved in complicated pregnancies echo those of CAD and stroke: inflammation, altered angiogenesis, vasculopathy, thrombosis, and insulin resistance. Still unsettled, however, is the chicken-versus-egg question of whether preeclampsia and other pregnancy complications represent the initial expression of an adverse phenotype associated with early development of cardiovascular disease or the complications injure the vascular endothelium and thereby trigger accelerated atherosclerosis. In any case, markers of endothelial activation have been documented up to 15 years after an episode of preeclampsia, Dr. Warnes said.
All of these data underscore the importance of identifying at-risk women based upon reproductive history, scheduling additional medical checkups so they don’t drop off the radar for the next 20 years, encouraging lifestyle modification, and giving consideration to early initiation of antihypertensive and lipid-lowering therapies.
“Pregnancy complications give us a glimpse of this awful disease trajectory at a time when women are completely asymptomatic and we could intervene and perhaps change outcomes with targeted therapy when it might be expected to work better and patients might be more receptive to such interventions,” she said.
Dr. Warnes reported having no financial conflicts of interest.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Aspirin for primary cardiovascular prevention, RIP
SNOWMASS, COLO. – during the space of a few short weeks in autumn 2018.
“Is aspirin safe and effective for primary prevention? The short answer here is no,” Patrick T. O’Gara, MD, declared at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Think of all those decades of aspirin therapy in the hopes of making ourselves healthier,” added Dr. O’Gara, professor of medicine at Harvard Medical School, Boston, and a past president of the American College of Cardiology.
He cited the results of three placebo-controlled randomized trials totaling more than 47,000 patients without known cardiovascular disease: ARRIVE, published in late September 2018, followed in October by ASPREE and ASCEND.
• ARRIVE. This double-blind study conducted in seven countries included 12,546 patients deemed at moderate cardiovascular risk, with an estimated 10-year cardiovascular event risk of 17%. Eligibility was restricted to men aged 55 and up and women aged 60 or older. After a median follow-up of 5 years, there was no difference between patients assigned to enteric-coated aspirin at 100 mg/day versus placebo in the incidence of major adverse cardiovascular events, with a hazard ratio of 0.96. However, GI bleeding events were 2.1-fold more common in the aspirin group (Lancet. 2018 Sep 22;392[10152]:1036-46).
• ASPREE. This double-blind trial, conducted in Australia and the United States, included 19,114 community-dwelling participants aged 70 years or older, or 65 years or older for Hispanics and blacks in the United States. After a median 4.7 years of follow-up, there was no difference in major adverse cardiovascular events between subjects randomized to 100 mg/day of enteric-coated aspirin and those on placebo. So, as in ARRIVE, no benefit. However, the rate of major hemorrhage was 38% greater in the aspirin group (N Engl J Med. 2018 Oct 18;379[16]:1509-18).
Moreover, the rate of all-cause mortality was 14% greater in the aspirin group, a statistically significant difference, compared with controls. Drilling down, the investigators showed that the major contributor to this excess mortality in the aspirin group was their 31% greater rate of cancer-related death (N Engl J Med. 2018 Oct 18;379[16]:1519-28).
“Remember, we used to think that taking aspirin reduced the incidence of GI cancer, and, in particular, colon adenocarcinoma? Well, here’s a very startling observation in 19,114 healthy elderly patients showing an increase in cancer-associated death with the use of aspirin,” commented Dr. O’Gara.
• ASCEND. This study randomized 15,480 subjects with diabetes but no known cardiovascular disease to 100 mg/day of aspirin or placebo and followed them for a mean of 7.4 years. There was a significant 12% relative risk reduction in the composite endpoint of serious vascular events in the aspirin group; however, the aspirin-treated patients also had a 29% greater rate of major bleeding events (N Engl J Med. 2018 Oct 18;379[16]:1529-39).
“So in dealing with our diabetic patients, we could perhaps say there is a small reduction in the risk of cardiovascular outcomes that is overwhelmed by more than a factor of two with regard to an increase in the risk of bleeding,” the cardiologist observed.
How did physicians get the aspirin story for primary prevention so wrong for so long? Dr. O’Gara pointed to the Physicians’ Health Study, conducted mainly back in the 1970s, as one of the benchmark studies that led to the widespread use of aspirin in this way.
“I think the aspirin story has now been put into sharp focus just within the course of the last 6 months and should force all of us to reassess what it is that we advise patients,” he concluded.
Dr. O’Gara’s presentation was the talk of the meeting, as many attendees hadn’t yet caught up with the latest aspirin data.
During an Q&A session, Robert A. Vogel, MD, a preventive cardiology authority at the University of Colorado, Denver, was asked, given the new emphasis placed upon coronary artery calcium as a supplemental risk assessment tool in the latest guidelines, at what magnitude of coronary artery calcium score in a patient with no history of coronary disease he would give aspirin for secondary prevention.
“I know I don’t know the answer to that question,” Dr. Vogel replied. “I no longer reflexively give aspirin to, say, a 60-year-old with a calcium score of 200. I will give a statin. Statins in my book are so effective and safe that my threshold for giving a statin in a 60-year-old is virtually nothing. But with a calcium score of 2,000 or 5,000, I worry just like you worry.”
He noted that the primary prevention patients in the three recent major trials were mostly 60-70 years of age or older. It’s safe to assume that by that point in life many of them had silent atherosclerosis and would have had a non-zero coronary artery calcium score, had they been tested. And yet, aspirin didn’t provide any net benefit in those groups, unlike the drug’s rock-solid proven value in patients who have actually experienced a cardiovascular event.
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
This article was updated 1/31/19.
SNOWMASS, COLO. – during the space of a few short weeks in autumn 2018.
“Is aspirin safe and effective for primary prevention? The short answer here is no,” Patrick T. O’Gara, MD, declared at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Think of all those decades of aspirin therapy in the hopes of making ourselves healthier,” added Dr. O’Gara, professor of medicine at Harvard Medical School, Boston, and a past president of the American College of Cardiology.
He cited the results of three placebo-controlled randomized trials totaling more than 47,000 patients without known cardiovascular disease: ARRIVE, published in late September 2018, followed in October by ASPREE and ASCEND.
• ARRIVE. This double-blind study conducted in seven countries included 12,546 patients deemed at moderate cardiovascular risk, with an estimated 10-year cardiovascular event risk of 17%. Eligibility was restricted to men aged 55 and up and women aged 60 or older. After a median follow-up of 5 years, there was no difference between patients assigned to enteric-coated aspirin at 100 mg/day versus placebo in the incidence of major adverse cardiovascular events, with a hazard ratio of 0.96. However, GI bleeding events were 2.1-fold more common in the aspirin group (Lancet. 2018 Sep 22;392[10152]:1036-46).
• ASPREE. This double-blind trial, conducted in Australia and the United States, included 19,114 community-dwelling participants aged 70 years or older, or 65 years or older for Hispanics and blacks in the United States. After a median 4.7 years of follow-up, there was no difference in major adverse cardiovascular events between subjects randomized to 100 mg/day of enteric-coated aspirin and those on placebo. So, as in ARRIVE, no benefit. However, the rate of major hemorrhage was 38% greater in the aspirin group (N Engl J Med. 2018 Oct 18;379[16]:1509-18).
Moreover, the rate of all-cause mortality was 14% greater in the aspirin group, a statistically significant difference, compared with controls. Drilling down, the investigators showed that the major contributor to this excess mortality in the aspirin group was their 31% greater rate of cancer-related death (N Engl J Med. 2018 Oct 18;379[16]:1519-28).
“Remember, we used to think that taking aspirin reduced the incidence of GI cancer, and, in particular, colon adenocarcinoma? Well, here’s a very startling observation in 19,114 healthy elderly patients showing an increase in cancer-associated death with the use of aspirin,” commented Dr. O’Gara.
• ASCEND. This study randomized 15,480 subjects with diabetes but no known cardiovascular disease to 100 mg/day of aspirin or placebo and followed them for a mean of 7.4 years. There was a significant 12% relative risk reduction in the composite endpoint of serious vascular events in the aspirin group; however, the aspirin-treated patients also had a 29% greater rate of major bleeding events (N Engl J Med. 2018 Oct 18;379[16]:1529-39).
“So in dealing with our diabetic patients, we could perhaps say there is a small reduction in the risk of cardiovascular outcomes that is overwhelmed by more than a factor of two with regard to an increase in the risk of bleeding,” the cardiologist observed.
How did physicians get the aspirin story for primary prevention so wrong for so long? Dr. O’Gara pointed to the Physicians’ Health Study, conducted mainly back in the 1970s, as one of the benchmark studies that led to the widespread use of aspirin in this way.
“I think the aspirin story has now been put into sharp focus just within the course of the last 6 months and should force all of us to reassess what it is that we advise patients,” he concluded.
Dr. O’Gara’s presentation was the talk of the meeting, as many attendees hadn’t yet caught up with the latest aspirin data.
During an Q&A session, Robert A. Vogel, MD, a preventive cardiology authority at the University of Colorado, Denver, was asked, given the new emphasis placed upon coronary artery calcium as a supplemental risk assessment tool in the latest guidelines, at what magnitude of coronary artery calcium score in a patient with no history of coronary disease he would give aspirin for secondary prevention.
“I know I don’t know the answer to that question,” Dr. Vogel replied. “I no longer reflexively give aspirin to, say, a 60-year-old with a calcium score of 200. I will give a statin. Statins in my book are so effective and safe that my threshold for giving a statin in a 60-year-old is virtually nothing. But with a calcium score of 2,000 or 5,000, I worry just like you worry.”
He noted that the primary prevention patients in the three recent major trials were mostly 60-70 years of age or older. It’s safe to assume that by that point in life many of them had silent atherosclerosis and would have had a non-zero coronary artery calcium score, had they been tested. And yet, aspirin didn’t provide any net benefit in those groups, unlike the drug’s rock-solid proven value in patients who have actually experienced a cardiovascular event.
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
This article was updated 1/31/19.
SNOWMASS, COLO. – during the space of a few short weeks in autumn 2018.
“Is aspirin safe and effective for primary prevention? The short answer here is no,” Patrick T. O’Gara, MD, declared at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Think of all those decades of aspirin therapy in the hopes of making ourselves healthier,” added Dr. O’Gara, professor of medicine at Harvard Medical School, Boston, and a past president of the American College of Cardiology.
He cited the results of three placebo-controlled randomized trials totaling more than 47,000 patients without known cardiovascular disease: ARRIVE, published in late September 2018, followed in October by ASPREE and ASCEND.
• ARRIVE. This double-blind study conducted in seven countries included 12,546 patients deemed at moderate cardiovascular risk, with an estimated 10-year cardiovascular event risk of 17%. Eligibility was restricted to men aged 55 and up and women aged 60 or older. After a median follow-up of 5 years, there was no difference between patients assigned to enteric-coated aspirin at 100 mg/day versus placebo in the incidence of major adverse cardiovascular events, with a hazard ratio of 0.96. However, GI bleeding events were 2.1-fold more common in the aspirin group (Lancet. 2018 Sep 22;392[10152]:1036-46).
• ASPREE. This double-blind trial, conducted in Australia and the United States, included 19,114 community-dwelling participants aged 70 years or older, or 65 years or older for Hispanics and blacks in the United States. After a median 4.7 years of follow-up, there was no difference in major adverse cardiovascular events between subjects randomized to 100 mg/day of enteric-coated aspirin and those on placebo. So, as in ARRIVE, no benefit. However, the rate of major hemorrhage was 38% greater in the aspirin group (N Engl J Med. 2018 Oct 18;379[16]:1509-18).
Moreover, the rate of all-cause mortality was 14% greater in the aspirin group, a statistically significant difference, compared with controls. Drilling down, the investigators showed that the major contributor to this excess mortality in the aspirin group was their 31% greater rate of cancer-related death (N Engl J Med. 2018 Oct 18;379[16]:1519-28).
“Remember, we used to think that taking aspirin reduced the incidence of GI cancer, and, in particular, colon adenocarcinoma? Well, here’s a very startling observation in 19,114 healthy elderly patients showing an increase in cancer-associated death with the use of aspirin,” commented Dr. O’Gara.
• ASCEND. This study randomized 15,480 subjects with diabetes but no known cardiovascular disease to 100 mg/day of aspirin or placebo and followed them for a mean of 7.4 years. There was a significant 12% relative risk reduction in the composite endpoint of serious vascular events in the aspirin group; however, the aspirin-treated patients also had a 29% greater rate of major bleeding events (N Engl J Med. 2018 Oct 18;379[16]:1529-39).
“So in dealing with our diabetic patients, we could perhaps say there is a small reduction in the risk of cardiovascular outcomes that is overwhelmed by more than a factor of two with regard to an increase in the risk of bleeding,” the cardiologist observed.
How did physicians get the aspirin story for primary prevention so wrong for so long? Dr. O’Gara pointed to the Physicians’ Health Study, conducted mainly back in the 1970s, as one of the benchmark studies that led to the widespread use of aspirin in this way.
“I think the aspirin story has now been put into sharp focus just within the course of the last 6 months and should force all of us to reassess what it is that we advise patients,” he concluded.
Dr. O’Gara’s presentation was the talk of the meeting, as many attendees hadn’t yet caught up with the latest aspirin data.
During an Q&A session, Robert A. Vogel, MD, a preventive cardiology authority at the University of Colorado, Denver, was asked, given the new emphasis placed upon coronary artery calcium as a supplemental risk assessment tool in the latest guidelines, at what magnitude of coronary artery calcium score in a patient with no history of coronary disease he would give aspirin for secondary prevention.
“I know I don’t know the answer to that question,” Dr. Vogel replied. “I no longer reflexively give aspirin to, say, a 60-year-old with a calcium score of 200. I will give a statin. Statins in my book are so effective and safe that my threshold for giving a statin in a 60-year-old is virtually nothing. But with a calcium score of 2,000 or 5,000, I worry just like you worry.”
He noted that the primary prevention patients in the three recent major trials were mostly 60-70 years of age or older. It’s safe to assume that by that point in life many of them had silent atherosclerosis and would have had a non-zero coronary artery calcium score, had they been tested. And yet, aspirin didn’t provide any net benefit in those groups, unlike the drug’s rock-solid proven value in patients who have actually experienced a cardiovascular event.
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
This article was updated 1/31/19.
REPORTING FROM ACC SNOWMASS 2019
Before you refer for AF ablation
SNOWMASS, COLO. – Appropriate in the way of benefit, along with instilling awareness of the warning signals heralding serious late complications, Samuel J. Asirvatham, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Who to steer toward ablation? You have to have a symptomatic patient – that’s a given. For the ones who are paroxysmal, the ones with a relatively normal heart, there’s a much better chance that you’ll help manage their symptoms with ablation than if they have persistent or permanent A-fib. Notice I do not use the word ‘cure’ for A-fib. We talk about controlling symptoms and decreasing frequency, because the longer follow-up you have with intensive monitoring, the more you realize that patients still tend to have some A-fib,” explained Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic in Rochester, Minn.
The rationale for early atrial fibrillation (AF) ablation in younger patients with troublesome symptoms of paroxysmal AF despite pharmacologic attempts at rate or rhythm control is that it will arrest the progression from an atrial arrhythmia that has just a few triggers readily neutralized by pulmonary vein isolation to persistent AF with a diseased heart and a multitude of arrhythmia trigger points coming from many directions.
A solid candidate for ablation of paroxysmal AF has about a 75% likelihood of having a successful first ablation procedure, with substantial improvement in symptoms and no need for medication. Another 9%-10% will achieve marked reduction in symptom burden upon addition of antiarrhythmic agents that weren’t effective before ablation.
Late complications can be deceptive
Periprocedural stroke/transient ischemic attack, tamponade, or bleeding on the table are infrequent complications readily recognized by the interventionalist. More problematic are several late complications which are often misinterpreted, with the resultant delay causing major harm.
- Pulmonary vein stenosis. This complication of inadvertent ablation inside the pulmonary vein manifests as shortness of breath, typically beginning about 4 weeks post ablation.
“This is very different from the shortness of breath they had with atrial fibrillation. They almost always have a cough that they didn’t have before, and they may have hemoptysis. It’s very important to recognize this promptly, because before it closes completely we can do an angioplasty and stent the vein with good results. But once it closes completely, it becomes an extremely complicated procedure to try to reopen that vein,” according to Dr. Asirvatham.
Very often the patient’s general cardiologist, chest physician, or primary care physician fails to recognize what’s happening. He cited an example: He recently had a patient with a cough who was first referred to an infectious disease specialist, who ordered a bronchoalveolar lavage. The specimen grew atypical actinomycetes. That prompted a referral to thoracic surgery for an open-lung biopsy. But that procedure required cardiac clearance beforehand. It was a cardiologist who said, ‘Wait – all this started after you had an ablation?’
“That patient had pulmonary vein stenosis. And, unfortunately, that complication has not gone away. Being a referral center for pulmonary vein isolation, we see just as many cases of pulmonary vein stenosis today as we did a few years ago,” he said.
- Atrial esophageal fistula. The hallmark of this complication is onset of a plethora of what Dr. Asirvatham called “funny symptoms” more than a month post ablation. These include fever, transient ischemic attacks (TIAs), sepsislike symptoms, discomfort in swallowing, and in some cases hemoptysis.
“The predominant picture is endocarditis/TIA/stroke. If you see this, and the patient has had ablation, immediately refer to surgery to have the fistula between the esophagus and heart fixed. This is not a patient where you say, ‘Nothing by mouth, give some antibiotics, and see what happens.’ I can tell you what will happen: The patient will die,” the cardiologist said.
- Atrial stiffness. This typically occurs about a month after a second or third ablation procedure, when the patient develops shortness of breath that keeps worsening.
“You think ‘pulmonary vein stenosis,’ but the CT scan shows the veins are wide open. Many of these patients will get misdiagnosed as having heart failure with preserved ejection fraction even though they never had it before. The problem here is the atrium has become too stiff from the ablation, and this stiff atrium causes increased pressure, resulting in the shortness of breath. Sometimes patients feel better over time, but sometimes it’s very difficult to treat. But it’s important to recognize atrial stiffness and exclude other causes like pulmonary vein stenosis,” Dr. Asirvatham continued.
- Gastroparesis. This occurs because of injury to the vagus nerve branches located at the top of the esophagus, with resultant delayed gastric emptying.
“It’s an uncomfortable feeling of fullness all the time. The patient will say, ‘It seems like I just ate, even though I ate 8 hours ago,” the electrophysiologist said. “Most of these patients will recover in about 6 months. They may feel better on a gastric motility agent, like a macrolide antibiotic. I personally have not seen a patient who did not feel better within 6-8 months.”
Novel treatment approaches: “A-fib may be an autonomic epilepsy of the heart”
“Patients sometimes will ask you, ‘What is this ablation? What does that mean?’ You have to be truthful and tell them that it’s just a fancy word for burning,” the electrophysiologist said.
Achievement of AF ablation without radiofrequency or cryoablation, instead utilizing nonthermal direct-current pulsed electrical fields, is “the hottest topic in the field of electrophysiology,” according to Dr. Asirvatham.
These electrical fields result in irreversible electroporation of targeted myocardial cell membranes, leading to cell death. It is a tissue-specific intervention, so it’s much less likely than conventional ablation to cause collateral damage to the esophagus and other structures.
“Direct current electroporation has transitioned from proof-of-concept studies to three relatively large patient trials. This is potentially an important breakthrough because if we don’t heat, a lot of the complications of A-fib ablation will probably decrease,” he explained.
Two other promising outside-the-box approaches to the treatment of AF are autonomic nervous system modulation at sites distant from the heart and particle beam ablation without need for cardiac catheters.
“If you put electrodes everywhere in the body to see where A-fib starts, it’s not in the atrium, not in the pulmonary veins, it’s in the nerves behind the pulmonary veins, and before those nerves it’s in some other area of the autonomic nervous system. This has given rise to the notion that A-fib may be an autonomic epilepsy of the heart,” according to the electrophysiologist.
This concept has given rise to a completely different approach to treatment of AF through neurostimulation. That’s how acupuncture works. Also, headphones have been used successfully to terminate and prevent AF by stimulating autonomic nerve centers near the ears. Low-level electrical stimulation of the vagus nerve in order to reduce stellate ganglion activity is under study. So is the application of botulinum toxin at key points in the autonomic nervous system.
“Catheters, drugs, and devices that target these areas, maybe without any ablation in the heart itself, is an exciting area of future management of A-fib,” he said.
Another promising approach is borrowed from radiation oncology: particulate ablation using beams of carbon atoms, protons, or photons.
“The first patients have now been treated for ventricular tachycardia and A-fib. It really is quite amazing how precise the lesion formation is. And with no catheters in the heart, clot can’t form on catheters,” he observed.
Dr. Asirvatham reported having no financial conflicts regarding his presentation, although he serves as a consultant to a handful of medical startup companies and holds patents on intellectual property, the royalties for which go directly to the Mayo Clinic.
SNOWMASS, COLO. – Appropriate in the way of benefit, along with instilling awareness of the warning signals heralding serious late complications, Samuel J. Asirvatham, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Who to steer toward ablation? You have to have a symptomatic patient – that’s a given. For the ones who are paroxysmal, the ones with a relatively normal heart, there’s a much better chance that you’ll help manage their symptoms with ablation than if they have persistent or permanent A-fib. Notice I do not use the word ‘cure’ for A-fib. We talk about controlling symptoms and decreasing frequency, because the longer follow-up you have with intensive monitoring, the more you realize that patients still tend to have some A-fib,” explained Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic in Rochester, Minn.
The rationale for early atrial fibrillation (AF) ablation in younger patients with troublesome symptoms of paroxysmal AF despite pharmacologic attempts at rate or rhythm control is that it will arrest the progression from an atrial arrhythmia that has just a few triggers readily neutralized by pulmonary vein isolation to persistent AF with a diseased heart and a multitude of arrhythmia trigger points coming from many directions.
A solid candidate for ablation of paroxysmal AF has about a 75% likelihood of having a successful first ablation procedure, with substantial improvement in symptoms and no need for medication. Another 9%-10% will achieve marked reduction in symptom burden upon addition of antiarrhythmic agents that weren’t effective before ablation.
Late complications can be deceptive
Periprocedural stroke/transient ischemic attack, tamponade, or bleeding on the table are infrequent complications readily recognized by the interventionalist. More problematic are several late complications which are often misinterpreted, with the resultant delay causing major harm.
- Pulmonary vein stenosis. This complication of inadvertent ablation inside the pulmonary vein manifests as shortness of breath, typically beginning about 4 weeks post ablation.
“This is very different from the shortness of breath they had with atrial fibrillation. They almost always have a cough that they didn’t have before, and they may have hemoptysis. It’s very important to recognize this promptly, because before it closes completely we can do an angioplasty and stent the vein with good results. But once it closes completely, it becomes an extremely complicated procedure to try to reopen that vein,” according to Dr. Asirvatham.
Very often the patient’s general cardiologist, chest physician, or primary care physician fails to recognize what’s happening. He cited an example: He recently had a patient with a cough who was first referred to an infectious disease specialist, who ordered a bronchoalveolar lavage. The specimen grew atypical actinomycetes. That prompted a referral to thoracic surgery for an open-lung biopsy. But that procedure required cardiac clearance beforehand. It was a cardiologist who said, ‘Wait – all this started after you had an ablation?’
“That patient had pulmonary vein stenosis. And, unfortunately, that complication has not gone away. Being a referral center for pulmonary vein isolation, we see just as many cases of pulmonary vein stenosis today as we did a few years ago,” he said.
- Atrial esophageal fistula. The hallmark of this complication is onset of a plethora of what Dr. Asirvatham called “funny symptoms” more than a month post ablation. These include fever, transient ischemic attacks (TIAs), sepsislike symptoms, discomfort in swallowing, and in some cases hemoptysis.
“The predominant picture is endocarditis/TIA/stroke. If you see this, and the patient has had ablation, immediately refer to surgery to have the fistula between the esophagus and heart fixed. This is not a patient where you say, ‘Nothing by mouth, give some antibiotics, and see what happens.’ I can tell you what will happen: The patient will die,” the cardiologist said.
- Atrial stiffness. This typically occurs about a month after a second or third ablation procedure, when the patient develops shortness of breath that keeps worsening.
“You think ‘pulmonary vein stenosis,’ but the CT scan shows the veins are wide open. Many of these patients will get misdiagnosed as having heart failure with preserved ejection fraction even though they never had it before. The problem here is the atrium has become too stiff from the ablation, and this stiff atrium causes increased pressure, resulting in the shortness of breath. Sometimes patients feel better over time, but sometimes it’s very difficult to treat. But it’s important to recognize atrial stiffness and exclude other causes like pulmonary vein stenosis,” Dr. Asirvatham continued.
- Gastroparesis. This occurs because of injury to the vagus nerve branches located at the top of the esophagus, with resultant delayed gastric emptying.
“It’s an uncomfortable feeling of fullness all the time. The patient will say, ‘It seems like I just ate, even though I ate 8 hours ago,” the electrophysiologist said. “Most of these patients will recover in about 6 months. They may feel better on a gastric motility agent, like a macrolide antibiotic. I personally have not seen a patient who did not feel better within 6-8 months.”
Novel treatment approaches: “A-fib may be an autonomic epilepsy of the heart”
“Patients sometimes will ask you, ‘What is this ablation? What does that mean?’ You have to be truthful and tell them that it’s just a fancy word for burning,” the electrophysiologist said.
Achievement of AF ablation without radiofrequency or cryoablation, instead utilizing nonthermal direct-current pulsed electrical fields, is “the hottest topic in the field of electrophysiology,” according to Dr. Asirvatham.
These electrical fields result in irreversible electroporation of targeted myocardial cell membranes, leading to cell death. It is a tissue-specific intervention, so it’s much less likely than conventional ablation to cause collateral damage to the esophagus and other structures.
“Direct current electroporation has transitioned from proof-of-concept studies to three relatively large patient trials. This is potentially an important breakthrough because if we don’t heat, a lot of the complications of A-fib ablation will probably decrease,” he explained.
Two other promising outside-the-box approaches to the treatment of AF are autonomic nervous system modulation at sites distant from the heart and particle beam ablation without need for cardiac catheters.
“If you put electrodes everywhere in the body to see where A-fib starts, it’s not in the atrium, not in the pulmonary veins, it’s in the nerves behind the pulmonary veins, and before those nerves it’s in some other area of the autonomic nervous system. This has given rise to the notion that A-fib may be an autonomic epilepsy of the heart,” according to the electrophysiologist.
This concept has given rise to a completely different approach to treatment of AF through neurostimulation. That’s how acupuncture works. Also, headphones have been used successfully to terminate and prevent AF by stimulating autonomic nerve centers near the ears. Low-level electrical stimulation of the vagus nerve in order to reduce stellate ganglion activity is under study. So is the application of botulinum toxin at key points in the autonomic nervous system.
“Catheters, drugs, and devices that target these areas, maybe without any ablation in the heart itself, is an exciting area of future management of A-fib,” he said.
Another promising approach is borrowed from radiation oncology: particulate ablation using beams of carbon atoms, protons, or photons.
“The first patients have now been treated for ventricular tachycardia and A-fib. It really is quite amazing how precise the lesion formation is. And with no catheters in the heart, clot can’t form on catheters,” he observed.
Dr. Asirvatham reported having no financial conflicts regarding his presentation, although he serves as a consultant to a handful of medical startup companies and holds patents on intellectual property, the royalties for which go directly to the Mayo Clinic.
SNOWMASS, COLO. – Appropriate in the way of benefit, along with instilling awareness of the warning signals heralding serious late complications, Samuel J. Asirvatham, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Who to steer toward ablation? You have to have a symptomatic patient – that’s a given. For the ones who are paroxysmal, the ones with a relatively normal heart, there’s a much better chance that you’ll help manage their symptoms with ablation than if they have persistent or permanent A-fib. Notice I do not use the word ‘cure’ for A-fib. We talk about controlling symptoms and decreasing frequency, because the longer follow-up you have with intensive monitoring, the more you realize that patients still tend to have some A-fib,” explained Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic in Rochester, Minn.
The rationale for early atrial fibrillation (AF) ablation in younger patients with troublesome symptoms of paroxysmal AF despite pharmacologic attempts at rate or rhythm control is that it will arrest the progression from an atrial arrhythmia that has just a few triggers readily neutralized by pulmonary vein isolation to persistent AF with a diseased heart and a multitude of arrhythmia trigger points coming from many directions.
A solid candidate for ablation of paroxysmal AF has about a 75% likelihood of having a successful first ablation procedure, with substantial improvement in symptoms and no need for medication. Another 9%-10% will achieve marked reduction in symptom burden upon addition of antiarrhythmic agents that weren’t effective before ablation.
Late complications can be deceptive
Periprocedural stroke/transient ischemic attack, tamponade, or bleeding on the table are infrequent complications readily recognized by the interventionalist. More problematic are several late complications which are often misinterpreted, with the resultant delay causing major harm.
- Pulmonary vein stenosis. This complication of inadvertent ablation inside the pulmonary vein manifests as shortness of breath, typically beginning about 4 weeks post ablation.
“This is very different from the shortness of breath they had with atrial fibrillation. They almost always have a cough that they didn’t have before, and they may have hemoptysis. It’s very important to recognize this promptly, because before it closes completely we can do an angioplasty and stent the vein with good results. But once it closes completely, it becomes an extremely complicated procedure to try to reopen that vein,” according to Dr. Asirvatham.
Very often the patient’s general cardiologist, chest physician, or primary care physician fails to recognize what’s happening. He cited an example: He recently had a patient with a cough who was first referred to an infectious disease specialist, who ordered a bronchoalveolar lavage. The specimen grew atypical actinomycetes. That prompted a referral to thoracic surgery for an open-lung biopsy. But that procedure required cardiac clearance beforehand. It was a cardiologist who said, ‘Wait – all this started after you had an ablation?’
“That patient had pulmonary vein stenosis. And, unfortunately, that complication has not gone away. Being a referral center for pulmonary vein isolation, we see just as many cases of pulmonary vein stenosis today as we did a few years ago,” he said.
- Atrial esophageal fistula. The hallmark of this complication is onset of a plethora of what Dr. Asirvatham called “funny symptoms” more than a month post ablation. These include fever, transient ischemic attacks (TIAs), sepsislike symptoms, discomfort in swallowing, and in some cases hemoptysis.
“The predominant picture is endocarditis/TIA/stroke. If you see this, and the patient has had ablation, immediately refer to surgery to have the fistula between the esophagus and heart fixed. This is not a patient where you say, ‘Nothing by mouth, give some antibiotics, and see what happens.’ I can tell you what will happen: The patient will die,” the cardiologist said.
- Atrial stiffness. This typically occurs about a month after a second or third ablation procedure, when the patient develops shortness of breath that keeps worsening.
“You think ‘pulmonary vein stenosis,’ but the CT scan shows the veins are wide open. Many of these patients will get misdiagnosed as having heart failure with preserved ejection fraction even though they never had it before. The problem here is the atrium has become too stiff from the ablation, and this stiff atrium causes increased pressure, resulting in the shortness of breath. Sometimes patients feel better over time, but sometimes it’s very difficult to treat. But it’s important to recognize atrial stiffness and exclude other causes like pulmonary vein stenosis,” Dr. Asirvatham continued.
- Gastroparesis. This occurs because of injury to the vagus nerve branches located at the top of the esophagus, with resultant delayed gastric emptying.
“It’s an uncomfortable feeling of fullness all the time. The patient will say, ‘It seems like I just ate, even though I ate 8 hours ago,” the electrophysiologist said. “Most of these patients will recover in about 6 months. They may feel better on a gastric motility agent, like a macrolide antibiotic. I personally have not seen a patient who did not feel better within 6-8 months.”
Novel treatment approaches: “A-fib may be an autonomic epilepsy of the heart”
“Patients sometimes will ask you, ‘What is this ablation? What does that mean?’ You have to be truthful and tell them that it’s just a fancy word for burning,” the electrophysiologist said.
Achievement of AF ablation without radiofrequency or cryoablation, instead utilizing nonthermal direct-current pulsed electrical fields, is “the hottest topic in the field of electrophysiology,” according to Dr. Asirvatham.
These electrical fields result in irreversible electroporation of targeted myocardial cell membranes, leading to cell death. It is a tissue-specific intervention, so it’s much less likely than conventional ablation to cause collateral damage to the esophagus and other structures.
“Direct current electroporation has transitioned from proof-of-concept studies to three relatively large patient trials. This is potentially an important breakthrough because if we don’t heat, a lot of the complications of A-fib ablation will probably decrease,” he explained.
Two other promising outside-the-box approaches to the treatment of AF are autonomic nervous system modulation at sites distant from the heart and particle beam ablation without need for cardiac catheters.
“If you put electrodes everywhere in the body to see where A-fib starts, it’s not in the atrium, not in the pulmonary veins, it’s in the nerves behind the pulmonary veins, and before those nerves it’s in some other area of the autonomic nervous system. This has given rise to the notion that A-fib may be an autonomic epilepsy of the heart,” according to the electrophysiologist.
This concept has given rise to a completely different approach to treatment of AF through neurostimulation. That’s how acupuncture works. Also, headphones have been used successfully to terminate and prevent AF by stimulating autonomic nerve centers near the ears. Low-level electrical stimulation of the vagus nerve in order to reduce stellate ganglion activity is under study. So is the application of botulinum toxin at key points in the autonomic nervous system.
“Catheters, drugs, and devices that target these areas, maybe without any ablation in the heart itself, is an exciting area of future management of A-fib,” he said.
Another promising approach is borrowed from radiation oncology: particulate ablation using beams of carbon atoms, protons, or photons.
“The first patients have now been treated for ventricular tachycardia and A-fib. It really is quite amazing how precise the lesion formation is. And with no catheters in the heart, clot can’t form on catheters,” he observed.
Dr. Asirvatham reported having no financial conflicts regarding his presentation, although he serves as a consultant to a handful of medical startup companies and holds patents on intellectual property, the royalties for which go directly to the Mayo Clinic.
REPORTING FROM ACC SNOWMASS 2019