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Caution urged in extending dual antiplatelet therapy
SNOWMASS, COLO. – Think very carefully before extending the duration of dual antiplatelet therapy beyond 6 months in drug-eluting stent recipients with stable ischemic heart disease, Patrick T. O’Gara, MD, advised at the Annual Cardiovascular Conference at Snowmass.
Six months of dual antiplatelet therapy (DAPT) in this setting received a Class I recommendation in the 2016 American College of Cardiology/American Heart Association guideline focused update on DAPT duration (J Am Coll Cardiol. 2016 Sep 6;68[10]:1082-115). That’s a departure from previous guidelines, which recommended 12 months of DAPT. The shortened DAPT duration of 6 months is consistent with European Society of Cardiology recommendations.
In contrast, extending DAPT beyond the 6-month mark garnered a relatively weak Class IIb recommendation in the ACC/AHA focused update, meaning it “could be considered,” noted Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
Considerable enthusiasm for extending DAPT well beyond 6 months after drug-eluting stent implantation has been generated in some quarters by the positive results of the PEGASUS TIMI 54 trial. But Dr. O’Gara and the other members of the guideline writing committee had reservations about the study, which together with other concerning evidence led to the weak Class IIb recommendation.
PEGASUS TIMI 54 included 21,162 patients with stable ischemic heart disease 1-3 years after a myocardial infarction who were randomized to low-dose aspirin plus either placebo or ticagrelor (Brilinta) at 60 mg or 90 mg b.i.d. and followed prospectively for a median of 33 months (N Engl J Med. 2015 May 7;372[19]:1791-800).
The primary efficacy endpoint, a composite of cardiovascular death, MI, or stroke, occurred in 9.0% of placebo-treated patients, compared with 7.8% of patients on either ticagrelor regimen, for a statistically significant 15% relative risk reduction in the DAPT group.
But there is more to the study than first meets the eye.
“I think what we as practitioners sometimes lose track of is that the investigators in this particular trial were very careful to enroll patients with stable ischemic heart disease who were at high risk of ischemic events over the next 3-5 years,” Dr. O’Gara noted. “These were patients who were generally older, patients with diabetes, chronic kidney disease, multivessel coronary disease, or who had had a second MI.”
Thus, the deck was stacked in favor of obtaining a result showing maximum efficacy. Yet, for every 10,000 patients treated with ticagrelor at 90 mg b.i.d., there were only 40 fewer cardiovascular events per year, compared with placebo. And that came at a cost of 41 more TIMI major bleeding events.
“That’s a wash at 90 mg,” the cardiologist said.
At 60 mg b.i.d. – the dose ultimately approved by the Food and Drug Administration – there were 42 fewer primary cardiovascular events per year per 10,000 treated patients, a benefit that came at the expense of 31 more TIMI major bleeding events.
“These are really razor thin margins, and I would encourage you to make a risk-benefit assessment of the trade-off between ischemia and bleeding in your decision-making,” Dr. O’Gara said.
The ACC/AHA guideline writing committee also took into account a meta-analysis of six randomized clinical trials totaling more than 33,000 high-risk patients post-MI who were assigned to more than 1 year of DAPT or aspirin alone. Extended DAPT brought a 22% reduction in the relative risk of major adverse cardiovascular events, but this was accompanied with a 73% increase in the risk of major bleeding (Eur Heart J. 2016 Jan 21;37[4]:390-9).
Turning to DAPT duration post-PCI in patients with an acute coronary syndrome, Dr. O’Gara noted that the 2016 ACC/AHA guideline focused update gave a Class I indication for 12 months of DAPT in recipients of a drug-eluting stent, but a weaker IIb recommendation for consideration of extending DAPT beyond that point – provided the patient was not at high bleeding risk and didn’t have significant bleeding during the first 12 months on DAPT.
“I think there’s a lot of individual and institutional variation with respect to this kind of decision-making, and I don’t think our guidelines are meant to be proscriptive, because our patients are quite nuanced,” the cardiologist observed.
The question physicians always have to ask in considering extended DAPT is, “How many ischemic events am I going to prevent at the expense of how many bleeding events?”
The investigators in the landmark DAPT study of extended therapy have analyzed their data in a fashion that has enabled them to develop a risk scoring system, known as the DAPT prediction rule, which is readily calculated based on factors including age, presence of diabetes, heart failure, and the size of the treated vessel.
For patients with a high DAPT score, assignment to an additional 18 months of DAPT after the initial 12 months of dual therapy was associated with a net 1.67% reduction in adverse events – both ischemic and bleeding – compared with the rate in patients who stopped DAPT at 12 months. For those with a low DAPT score, extended dual antiplatelet therapy resulted in a 1.03% net increase in adverse events (JAMA. 2016 Apr 26;315[16]:1735-49).
“I should warn you that the discriminatory power of this particular score is relatively modest,” Dr. O’Gara noted. “The C-statistic is not higher than about 0.7. But I do think that the DAPT score meets the sniff test biologically and clinically. It’s a real good first step. I do think this particular score needs to be validated externally in other populations going forward.”
Dr. O’Gara reported having no financial conflicts of interest.
SNOWMASS, COLO. – Think very carefully before extending the duration of dual antiplatelet therapy beyond 6 months in drug-eluting stent recipients with stable ischemic heart disease, Patrick T. O’Gara, MD, advised at the Annual Cardiovascular Conference at Snowmass.
Six months of dual antiplatelet therapy (DAPT) in this setting received a Class I recommendation in the 2016 American College of Cardiology/American Heart Association guideline focused update on DAPT duration (J Am Coll Cardiol. 2016 Sep 6;68[10]:1082-115). That’s a departure from previous guidelines, which recommended 12 months of DAPT. The shortened DAPT duration of 6 months is consistent with European Society of Cardiology recommendations.
In contrast, extending DAPT beyond the 6-month mark garnered a relatively weak Class IIb recommendation in the ACC/AHA focused update, meaning it “could be considered,” noted Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
Considerable enthusiasm for extending DAPT well beyond 6 months after drug-eluting stent implantation has been generated in some quarters by the positive results of the PEGASUS TIMI 54 trial. But Dr. O’Gara and the other members of the guideline writing committee had reservations about the study, which together with other concerning evidence led to the weak Class IIb recommendation.
PEGASUS TIMI 54 included 21,162 patients with stable ischemic heart disease 1-3 years after a myocardial infarction who were randomized to low-dose aspirin plus either placebo or ticagrelor (Brilinta) at 60 mg or 90 mg b.i.d. and followed prospectively for a median of 33 months (N Engl J Med. 2015 May 7;372[19]:1791-800).
The primary efficacy endpoint, a composite of cardiovascular death, MI, or stroke, occurred in 9.0% of placebo-treated patients, compared with 7.8% of patients on either ticagrelor regimen, for a statistically significant 15% relative risk reduction in the DAPT group.
But there is more to the study than first meets the eye.
“I think what we as practitioners sometimes lose track of is that the investigators in this particular trial were very careful to enroll patients with stable ischemic heart disease who were at high risk of ischemic events over the next 3-5 years,” Dr. O’Gara noted. “These were patients who were generally older, patients with diabetes, chronic kidney disease, multivessel coronary disease, or who had had a second MI.”
Thus, the deck was stacked in favor of obtaining a result showing maximum efficacy. Yet, for every 10,000 patients treated with ticagrelor at 90 mg b.i.d., there were only 40 fewer cardiovascular events per year, compared with placebo. And that came at a cost of 41 more TIMI major bleeding events.
“That’s a wash at 90 mg,” the cardiologist said.
At 60 mg b.i.d. – the dose ultimately approved by the Food and Drug Administration – there were 42 fewer primary cardiovascular events per year per 10,000 treated patients, a benefit that came at the expense of 31 more TIMI major bleeding events.
“These are really razor thin margins, and I would encourage you to make a risk-benefit assessment of the trade-off between ischemia and bleeding in your decision-making,” Dr. O’Gara said.
The ACC/AHA guideline writing committee also took into account a meta-analysis of six randomized clinical trials totaling more than 33,000 high-risk patients post-MI who were assigned to more than 1 year of DAPT or aspirin alone. Extended DAPT brought a 22% reduction in the relative risk of major adverse cardiovascular events, but this was accompanied with a 73% increase in the risk of major bleeding (Eur Heart J. 2016 Jan 21;37[4]:390-9).
Turning to DAPT duration post-PCI in patients with an acute coronary syndrome, Dr. O’Gara noted that the 2016 ACC/AHA guideline focused update gave a Class I indication for 12 months of DAPT in recipients of a drug-eluting stent, but a weaker IIb recommendation for consideration of extending DAPT beyond that point – provided the patient was not at high bleeding risk and didn’t have significant bleeding during the first 12 months on DAPT.
“I think there’s a lot of individual and institutional variation with respect to this kind of decision-making, and I don’t think our guidelines are meant to be proscriptive, because our patients are quite nuanced,” the cardiologist observed.
The question physicians always have to ask in considering extended DAPT is, “How many ischemic events am I going to prevent at the expense of how many bleeding events?”
The investigators in the landmark DAPT study of extended therapy have analyzed their data in a fashion that has enabled them to develop a risk scoring system, known as the DAPT prediction rule, which is readily calculated based on factors including age, presence of diabetes, heart failure, and the size of the treated vessel.
For patients with a high DAPT score, assignment to an additional 18 months of DAPT after the initial 12 months of dual therapy was associated with a net 1.67% reduction in adverse events – both ischemic and bleeding – compared with the rate in patients who stopped DAPT at 12 months. For those with a low DAPT score, extended dual antiplatelet therapy resulted in a 1.03% net increase in adverse events (JAMA. 2016 Apr 26;315[16]:1735-49).
“I should warn you that the discriminatory power of this particular score is relatively modest,” Dr. O’Gara noted. “The C-statistic is not higher than about 0.7. But I do think that the DAPT score meets the sniff test biologically and clinically. It’s a real good first step. I do think this particular score needs to be validated externally in other populations going forward.”
Dr. O’Gara reported having no financial conflicts of interest.
SNOWMASS, COLO. – Think very carefully before extending the duration of dual antiplatelet therapy beyond 6 months in drug-eluting stent recipients with stable ischemic heart disease, Patrick T. O’Gara, MD, advised at the Annual Cardiovascular Conference at Snowmass.
Six months of dual antiplatelet therapy (DAPT) in this setting received a Class I recommendation in the 2016 American College of Cardiology/American Heart Association guideline focused update on DAPT duration (J Am Coll Cardiol. 2016 Sep 6;68[10]:1082-115). That’s a departure from previous guidelines, which recommended 12 months of DAPT. The shortened DAPT duration of 6 months is consistent with European Society of Cardiology recommendations.
In contrast, extending DAPT beyond the 6-month mark garnered a relatively weak Class IIb recommendation in the ACC/AHA focused update, meaning it “could be considered,” noted Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
Considerable enthusiasm for extending DAPT well beyond 6 months after drug-eluting stent implantation has been generated in some quarters by the positive results of the PEGASUS TIMI 54 trial. But Dr. O’Gara and the other members of the guideline writing committee had reservations about the study, which together with other concerning evidence led to the weak Class IIb recommendation.
PEGASUS TIMI 54 included 21,162 patients with stable ischemic heart disease 1-3 years after a myocardial infarction who were randomized to low-dose aspirin plus either placebo or ticagrelor (Brilinta) at 60 mg or 90 mg b.i.d. and followed prospectively for a median of 33 months (N Engl J Med. 2015 May 7;372[19]:1791-800).
The primary efficacy endpoint, a composite of cardiovascular death, MI, or stroke, occurred in 9.0% of placebo-treated patients, compared with 7.8% of patients on either ticagrelor regimen, for a statistically significant 15% relative risk reduction in the DAPT group.
But there is more to the study than first meets the eye.
“I think what we as practitioners sometimes lose track of is that the investigators in this particular trial were very careful to enroll patients with stable ischemic heart disease who were at high risk of ischemic events over the next 3-5 years,” Dr. O’Gara noted. “These were patients who were generally older, patients with diabetes, chronic kidney disease, multivessel coronary disease, or who had had a second MI.”
Thus, the deck was stacked in favor of obtaining a result showing maximum efficacy. Yet, for every 10,000 patients treated with ticagrelor at 90 mg b.i.d., there were only 40 fewer cardiovascular events per year, compared with placebo. And that came at a cost of 41 more TIMI major bleeding events.
“That’s a wash at 90 mg,” the cardiologist said.
At 60 mg b.i.d. – the dose ultimately approved by the Food and Drug Administration – there were 42 fewer primary cardiovascular events per year per 10,000 treated patients, a benefit that came at the expense of 31 more TIMI major bleeding events.
“These are really razor thin margins, and I would encourage you to make a risk-benefit assessment of the trade-off between ischemia and bleeding in your decision-making,” Dr. O’Gara said.
The ACC/AHA guideline writing committee also took into account a meta-analysis of six randomized clinical trials totaling more than 33,000 high-risk patients post-MI who were assigned to more than 1 year of DAPT or aspirin alone. Extended DAPT brought a 22% reduction in the relative risk of major adverse cardiovascular events, but this was accompanied with a 73% increase in the risk of major bleeding (Eur Heart J. 2016 Jan 21;37[4]:390-9).
Turning to DAPT duration post-PCI in patients with an acute coronary syndrome, Dr. O’Gara noted that the 2016 ACC/AHA guideline focused update gave a Class I indication for 12 months of DAPT in recipients of a drug-eluting stent, but a weaker IIb recommendation for consideration of extending DAPT beyond that point – provided the patient was not at high bleeding risk and didn’t have significant bleeding during the first 12 months on DAPT.
“I think there’s a lot of individual and institutional variation with respect to this kind of decision-making, and I don’t think our guidelines are meant to be proscriptive, because our patients are quite nuanced,” the cardiologist observed.
The question physicians always have to ask in considering extended DAPT is, “How many ischemic events am I going to prevent at the expense of how many bleeding events?”
The investigators in the landmark DAPT study of extended therapy have analyzed their data in a fashion that has enabled them to develop a risk scoring system, known as the DAPT prediction rule, which is readily calculated based on factors including age, presence of diabetes, heart failure, and the size of the treated vessel.
For patients with a high DAPT score, assignment to an additional 18 months of DAPT after the initial 12 months of dual therapy was associated with a net 1.67% reduction in adverse events – both ischemic and bleeding – compared with the rate in patients who stopped DAPT at 12 months. For those with a low DAPT score, extended dual antiplatelet therapy resulted in a 1.03% net increase in adverse events (JAMA. 2016 Apr 26;315[16]:1735-49).
“I should warn you that the discriminatory power of this particular score is relatively modest,” Dr. O’Gara noted. “The C-statistic is not higher than about 0.7. But I do think that the DAPT score meets the sniff test biologically and clinically. It’s a real good first step. I do think this particular score needs to be validated externally in other populations going forward.”
Dr. O’Gara reported having no financial conflicts of interest.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Coronary flow reserve reveals hidden cardiovascular risk
SNOWMASS, COLO. – Mounting evidence attests to the value of noninvasive measurement of coronary flow reserve as a means of classifying cardiovascular risk in patients with stable coronary artery disease (CAD) more accurately than is possible via coronary angiography or measurement of fractional flow reserve, Marcelo F. Di Carli, MD, reported at the Annual Cardiovascular Conference at Snowmass.
“We use CFR [coronary flow reserve] as a way to exclude coronary disease. It’s a good practical measure of multivessel ischemic CAD. When the CFR is normal, you can with high confidence exclude the possibility of high-risk CAD,” according to Dr. Di Carli, executive director of the cardiovascular imaging program and chief of the division of nuclear medicine and molecular imaging at Brigham and Women’s Hospital, Boston.
Most recently, he and his coinvestigators utilized CFR to provide new insight into the paradox that women have a higher cardiovascular disease death rate than men, even though their prevalence of obstructive CAD is lower.
Their NIH-sponsored study included 329 consecutive patients with a left ventricular ejection fraction greater than 40% – 43% of them women – who underwent coronary angiography several days after noninvasive assessment of CFR via myocardial perfusion positron emission tomography. The women had a lower burden of angiographic CAD and a lower pretest clinical risk score than the men. Nevertheless, during a median of 3 years of follow-up, the women had an adjusted twofold greater risk of the composite endpoint of cardiovascular death, nonfatal MI, or heart failure.
This excess cardiovascular risk in women was independently associated with a very low CFR, defined as less than 1.6. Dr. Di Carli and his coinvestigators calculated that this impaired CFR mediated 40% of the excess risk in women. Thus, a low CFR represents a novel hidden biologic risk for ischemic heart disease (Circulation. 2017 Feb 7;135[6]:566-77).
CFR is defined as the ratio of absolute coronary flow or myocardial perfusion between drug-induced hyperemia and rest. It can be quantified noninvasively using positron emission tomography or MRI.
CFR integrates into a single measure the three components of CAD: the focal stenosis, the diffuse atherosclerotic plaque typically present to a varying degree throughout a target vessel, and microvascular dysfunction.
CFR is a measure of coronary physiology, as is invasive fractional flow reserve (FFR). However, FFR measures only the severity of stenosis and extent of diffuse disease; it doesn’t assess microvascular dysfunction. This is a limitation because it means FFR can give false-negative readings in patients without significant obstructive coronary disease who have severe microvascular dysfunction.
As for angiography, Dr. Di Carli continued, it’s now evident that this purely anatomic assessment is of limited value as a marker of clinical risk and is inadequate to guide management decisions in the setting of stable CAD. After all, angiographically guided revascularization has not reduced cardiovascular events in clinical trials comparing it with optimal medical therapy, as in the COURAGE and BARI-2D trials.
“It’s clear that there’s been a paradigm shift in how we manage patients with stable CAD. For many years the coronary angiogram was the cornerstone of what we did: how we understand the symptoms, the patient’s risk, and ultimately how we proceed with treatment. But there is no benefit in basing treatment solely on what the lesions look like anatomically. That’s why we’ve turned to functional testing of coronary physiology,” he said.
CFR has opened a window on the importance of microvascular dysfunction, which is present in about half of patients with stable CAD and has been shown to predict cardiovascular risk independent of whether or not severe obstructive disease is present.
In an earlier study, Dr. Di Carli and coworkers demonstrated that quantification of CFR enhances stratification for risk of cardiac death among diabetes patients (Circulation. 2012 Oct 9;126[15]:1858-68). The study included 2,783 patients, of whom 1,172 were diabetic, who underwent measurement of CFR and were subsequently followed for a median of 1.4 years, during which 137 cardiac deaths occurred.
Diabetes patients without known CAD who had a low CFR had a high cardiac death rate of 2.8%/year, similar to the 2.0%/year rate in nondiabetic patients with a history of acute MI or revascularization. On the other hand, diabetes patients with a normal CFR and without known CAD had a cardiac mortality rate of only 0.3%/year, comparable to the 0.5% rate in nondiabetics without known CAD who had preserved systolic function and a normal stress perfusion study.
In the future, CFR may aid in decision making as to whether an individual with stable CAD is best treated by percutaneous coronary intervention, surgical revascularization, or guideline-directed medical therapy. For example, if CFR indicates the presence of an isolated severe focal stenosis, and this is confirmed by angiography and FFR, PCI may be the best option, while diffuse disease as demonstrated by CFR may be better treated surgically or using optimal medical therapy. But this needs to be established in prospective clinical trials, added Dr. Di Carli.
He reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – Mounting evidence attests to the value of noninvasive measurement of coronary flow reserve as a means of classifying cardiovascular risk in patients with stable coronary artery disease (CAD) more accurately than is possible via coronary angiography or measurement of fractional flow reserve, Marcelo F. Di Carli, MD, reported at the Annual Cardiovascular Conference at Snowmass.
“We use CFR [coronary flow reserve] as a way to exclude coronary disease. It’s a good practical measure of multivessel ischemic CAD. When the CFR is normal, you can with high confidence exclude the possibility of high-risk CAD,” according to Dr. Di Carli, executive director of the cardiovascular imaging program and chief of the division of nuclear medicine and molecular imaging at Brigham and Women’s Hospital, Boston.
Most recently, he and his coinvestigators utilized CFR to provide new insight into the paradox that women have a higher cardiovascular disease death rate than men, even though their prevalence of obstructive CAD is lower.
Their NIH-sponsored study included 329 consecutive patients with a left ventricular ejection fraction greater than 40% – 43% of them women – who underwent coronary angiography several days after noninvasive assessment of CFR via myocardial perfusion positron emission tomography. The women had a lower burden of angiographic CAD and a lower pretest clinical risk score than the men. Nevertheless, during a median of 3 years of follow-up, the women had an adjusted twofold greater risk of the composite endpoint of cardiovascular death, nonfatal MI, or heart failure.
This excess cardiovascular risk in women was independently associated with a very low CFR, defined as less than 1.6. Dr. Di Carli and his coinvestigators calculated that this impaired CFR mediated 40% of the excess risk in women. Thus, a low CFR represents a novel hidden biologic risk for ischemic heart disease (Circulation. 2017 Feb 7;135[6]:566-77).
CFR is defined as the ratio of absolute coronary flow or myocardial perfusion between drug-induced hyperemia and rest. It can be quantified noninvasively using positron emission tomography or MRI.
CFR integrates into a single measure the three components of CAD: the focal stenosis, the diffuse atherosclerotic plaque typically present to a varying degree throughout a target vessel, and microvascular dysfunction.
CFR is a measure of coronary physiology, as is invasive fractional flow reserve (FFR). However, FFR measures only the severity of stenosis and extent of diffuse disease; it doesn’t assess microvascular dysfunction. This is a limitation because it means FFR can give false-negative readings in patients without significant obstructive coronary disease who have severe microvascular dysfunction.
As for angiography, Dr. Di Carli continued, it’s now evident that this purely anatomic assessment is of limited value as a marker of clinical risk and is inadequate to guide management decisions in the setting of stable CAD. After all, angiographically guided revascularization has not reduced cardiovascular events in clinical trials comparing it with optimal medical therapy, as in the COURAGE and BARI-2D trials.
“It’s clear that there’s been a paradigm shift in how we manage patients with stable CAD. For many years the coronary angiogram was the cornerstone of what we did: how we understand the symptoms, the patient’s risk, and ultimately how we proceed with treatment. But there is no benefit in basing treatment solely on what the lesions look like anatomically. That’s why we’ve turned to functional testing of coronary physiology,” he said.
CFR has opened a window on the importance of microvascular dysfunction, which is present in about half of patients with stable CAD and has been shown to predict cardiovascular risk independent of whether or not severe obstructive disease is present.
In an earlier study, Dr. Di Carli and coworkers demonstrated that quantification of CFR enhances stratification for risk of cardiac death among diabetes patients (Circulation. 2012 Oct 9;126[15]:1858-68). The study included 2,783 patients, of whom 1,172 were diabetic, who underwent measurement of CFR and were subsequently followed for a median of 1.4 years, during which 137 cardiac deaths occurred.
Diabetes patients without known CAD who had a low CFR had a high cardiac death rate of 2.8%/year, similar to the 2.0%/year rate in nondiabetic patients with a history of acute MI or revascularization. On the other hand, diabetes patients with a normal CFR and without known CAD had a cardiac mortality rate of only 0.3%/year, comparable to the 0.5% rate in nondiabetics without known CAD who had preserved systolic function and a normal stress perfusion study.
In the future, CFR may aid in decision making as to whether an individual with stable CAD is best treated by percutaneous coronary intervention, surgical revascularization, or guideline-directed medical therapy. For example, if CFR indicates the presence of an isolated severe focal stenosis, and this is confirmed by angiography and FFR, PCI may be the best option, while diffuse disease as demonstrated by CFR may be better treated surgically or using optimal medical therapy. But this needs to be established in prospective clinical trials, added Dr. Di Carli.
He reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – Mounting evidence attests to the value of noninvasive measurement of coronary flow reserve as a means of classifying cardiovascular risk in patients with stable coronary artery disease (CAD) more accurately than is possible via coronary angiography or measurement of fractional flow reserve, Marcelo F. Di Carli, MD, reported at the Annual Cardiovascular Conference at Snowmass.
“We use CFR [coronary flow reserve] as a way to exclude coronary disease. It’s a good practical measure of multivessel ischemic CAD. When the CFR is normal, you can with high confidence exclude the possibility of high-risk CAD,” according to Dr. Di Carli, executive director of the cardiovascular imaging program and chief of the division of nuclear medicine and molecular imaging at Brigham and Women’s Hospital, Boston.
Most recently, he and his coinvestigators utilized CFR to provide new insight into the paradox that women have a higher cardiovascular disease death rate than men, even though their prevalence of obstructive CAD is lower.
Their NIH-sponsored study included 329 consecutive patients with a left ventricular ejection fraction greater than 40% – 43% of them women – who underwent coronary angiography several days after noninvasive assessment of CFR via myocardial perfusion positron emission tomography. The women had a lower burden of angiographic CAD and a lower pretest clinical risk score than the men. Nevertheless, during a median of 3 years of follow-up, the women had an adjusted twofold greater risk of the composite endpoint of cardiovascular death, nonfatal MI, or heart failure.
This excess cardiovascular risk in women was independently associated with a very low CFR, defined as less than 1.6. Dr. Di Carli and his coinvestigators calculated that this impaired CFR mediated 40% of the excess risk in women. Thus, a low CFR represents a novel hidden biologic risk for ischemic heart disease (Circulation. 2017 Feb 7;135[6]:566-77).
CFR is defined as the ratio of absolute coronary flow or myocardial perfusion between drug-induced hyperemia and rest. It can be quantified noninvasively using positron emission tomography or MRI.
CFR integrates into a single measure the three components of CAD: the focal stenosis, the diffuse atherosclerotic plaque typically present to a varying degree throughout a target vessel, and microvascular dysfunction.
CFR is a measure of coronary physiology, as is invasive fractional flow reserve (FFR). However, FFR measures only the severity of stenosis and extent of diffuse disease; it doesn’t assess microvascular dysfunction. This is a limitation because it means FFR can give false-negative readings in patients without significant obstructive coronary disease who have severe microvascular dysfunction.
As for angiography, Dr. Di Carli continued, it’s now evident that this purely anatomic assessment is of limited value as a marker of clinical risk and is inadequate to guide management decisions in the setting of stable CAD. After all, angiographically guided revascularization has not reduced cardiovascular events in clinical trials comparing it with optimal medical therapy, as in the COURAGE and BARI-2D trials.
“It’s clear that there’s been a paradigm shift in how we manage patients with stable CAD. For many years the coronary angiogram was the cornerstone of what we did: how we understand the symptoms, the patient’s risk, and ultimately how we proceed with treatment. But there is no benefit in basing treatment solely on what the lesions look like anatomically. That’s why we’ve turned to functional testing of coronary physiology,” he said.
CFR has opened a window on the importance of microvascular dysfunction, which is present in about half of patients with stable CAD and has been shown to predict cardiovascular risk independent of whether or not severe obstructive disease is present.
In an earlier study, Dr. Di Carli and coworkers demonstrated that quantification of CFR enhances stratification for risk of cardiac death among diabetes patients (Circulation. 2012 Oct 9;126[15]:1858-68). The study included 2,783 patients, of whom 1,172 were diabetic, who underwent measurement of CFR and were subsequently followed for a median of 1.4 years, during which 137 cardiac deaths occurred.
Diabetes patients without known CAD who had a low CFR had a high cardiac death rate of 2.8%/year, similar to the 2.0%/year rate in nondiabetic patients with a history of acute MI or revascularization. On the other hand, diabetes patients with a normal CFR and without known CAD had a cardiac mortality rate of only 0.3%/year, comparable to the 0.5% rate in nondiabetics without known CAD who had preserved systolic function and a normal stress perfusion study.
In the future, CFR may aid in decision making as to whether an individual with stable CAD is best treated by percutaneous coronary intervention, surgical revascularization, or guideline-directed medical therapy. For example, if CFR indicates the presence of an isolated severe focal stenosis, and this is confirmed by angiography and FFR, PCI may be the best option, while diffuse disease as demonstrated by CFR may be better treated surgically or using optimal medical therapy. But this needs to be established in prospective clinical trials, added Dr. Di Carli.
He reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Uptake of new heart failure drugs slow despite guidelines
SNOWMASS, COLO. – As William T. Abraham, MD, speaks to colleagues around the country about heart failure therapy, he has noticed that the first-in-class drug ivabradine remains below the radar of most physicians.
“I’ve found that this is an agent that very few people know about, even though it’s been FDA [Food and Drug Administration] approved for about 3 years. It’s used fairly extensively in Europe because that’s where the pivotal SHIFT trial was done, but not very much in the United States,” according to Dr. Abraham, professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus.
That’s likely to change as word spreads about the May 2016 update of the American College of Cardiology/American Heart Association Guideline for the Management of Heart Failure. The update incorporated evidence-based recommendations on the use of two important new heart failure medications: ivabradine (Corlanor), which received a moderate class IIa recommendation, meaning the drug “should be considered,” and sacubitril/valsartan (Entresto), which received the strongest class I recommendation.
In the right patients, these two oral medications improve heart failure morbidity and mortality significantly beyond what’s achievable with what has been the gold standard, guideline-directed medical therapy. Dr. Abraham described how to get started using the two medications at the Annual Cardiovascular Conference at Snowmass.
Ivabradine
Ivabradine is a selective inhibitor of the sinoatrial pacemaker modulating I(f) current. It acts by slowing the sinus rate without reducing myocardial contractility.
“This agent does one thing and one thing alone: It lowers heart rate,” the cardiologist explained.
And that, he added, was sufficient to significantly reduce the risks of death due to heart failure and recurrent hospitalization for worsening heart failure in the pivotal SHIFT trial.
SHIFT included 6,505 patients with moderate to severe heart failure with reduced left ventricular ejection fraction (LVEF) and a resting heart rate above 70 bpm despite background guideline-directed medical therapy. Participants were randomized double blind to ivabradine titrated to a maximum of 7.5 mg twice daily or placebo and followed for a median of about 23 months. The rate of death due to heart failure was 3% with ivabradine and 5% with placebo, for a statistically significant 26% relative risk reduction favoring ivabradine.
But the drug’s main benefit was in reducing recurrent hospitalizations for heart failure, an endpoint of particular interest to health policy officials given that heart failure hospitalizations chew up a substantial proportion of the Medicare budget. Ivabradine reduced first hospitalizations for heart failure during the study period by 25%, second hospitalizations by 34%, and third hospitalizations by 29% (Eur Heart J. 2012 Nov;33[22]:2813-20).
The ACC/AHA guideline update stresses the importance of reserving ivabradine for heart failure patients whose resting heart rate exceeds 70 bpm, despite being on their maximum tolerated dose of a beta-blocker, Dr. Abraham noted.
Ivabradine is contraindicated in the setting of acute decompensated heart failure, severe liver disease, or hypotension, in patients on any of the numerous agents that strongly inhibit the enzyme cytochrome P450 3A4, and in those who have sick sinus syndrome, have sinoatrial block, or are pacemaker dependent.
Sacubitril/valsartan
Sacubitril inhibits neprilysin, an enzyme that blocks the action of endogenous vasoactive peptides including bradykinin, substance P, and natriuretic peptides, all of which counter important maladaptive mechanisms in heart failure. Sacubitril has been combined with the angiotensin receptor blocker valsartan to form the first-in-class angiotensin receptor neprilysin inhibitor, or ARNI, formerly known as LCZ696 and now marketed as Entresto.
In the pivotal double-blind PARADIGM-HF trial, 8,442 patients with heart failure with reduced ejection fraction were randomized to the ARNI at 200 mg b.i.d. or to enalapril at 10 mg b.i.d. on top of background guideline-directed medical therapy. The trial was stopped early because of evidence of overwhelming benefit: a 20% relative risk reduction in cardiovascular death and a 21% decrease in the risk of heart failure hospitalizations in the sacubitril/valsartan group, as well as significant reductions in heart failure symptoms and physical limitations (N Engl J Med. 2014 Sep 11;371[11]:993-1004).
The updated heart failure guidelines strongly recommend that patients with heart failure should be treated with either an ACE inhibitor, an angiotensin receptor blocker, or an ARNI. Further, patients who remain symptomatic on an ACE inhibitor or angiotensin receptor blocker should be switched to an ARNI; that’s a class Ib recommendation based upon the results of PARADIGM-HF.
In getting started using the ARNI, Dr. Abraham said it’s important to understand as background the selective nature of the PARADIGM-HF study design. During the single-blind run-in period of 5-8 weeks, roughly 10% of patients dropped out because they couldn’t tolerate enalapril at 10 mg b.i.d., and a similar percentage dropped out during the ARNI run-in. Thus, patients who couldn’t tolerate a low dose of an ACE inhibitor weren’t in the study. And patients capable of tolerating guideline-recommended full-dose ACE inhibitor therapy were not specifically sought for participation.
“So there are some unanswered questions about the ARNI. If you’re just getting started with this compound in treating your heart failure patients, my own feeling is you should maybe aim for the type of patient that was included in this trial: patients who could tolerate a moderate dose of an ACE inhibitor and had generally good blood pressure. That’s a great way to begin to get experience with this agent in heart failure,” the cardiologist advised.
He reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – As William T. Abraham, MD, speaks to colleagues around the country about heart failure therapy, he has noticed that the first-in-class drug ivabradine remains below the radar of most physicians.
“I’ve found that this is an agent that very few people know about, even though it’s been FDA [Food and Drug Administration] approved for about 3 years. It’s used fairly extensively in Europe because that’s where the pivotal SHIFT trial was done, but not very much in the United States,” according to Dr. Abraham, professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus.
That’s likely to change as word spreads about the May 2016 update of the American College of Cardiology/American Heart Association Guideline for the Management of Heart Failure. The update incorporated evidence-based recommendations on the use of two important new heart failure medications: ivabradine (Corlanor), which received a moderate class IIa recommendation, meaning the drug “should be considered,” and sacubitril/valsartan (Entresto), which received the strongest class I recommendation.
In the right patients, these two oral medications improve heart failure morbidity and mortality significantly beyond what’s achievable with what has been the gold standard, guideline-directed medical therapy. Dr. Abraham described how to get started using the two medications at the Annual Cardiovascular Conference at Snowmass.
Ivabradine
Ivabradine is a selective inhibitor of the sinoatrial pacemaker modulating I(f) current. It acts by slowing the sinus rate without reducing myocardial contractility.
“This agent does one thing and one thing alone: It lowers heart rate,” the cardiologist explained.
And that, he added, was sufficient to significantly reduce the risks of death due to heart failure and recurrent hospitalization for worsening heart failure in the pivotal SHIFT trial.
SHIFT included 6,505 patients with moderate to severe heart failure with reduced left ventricular ejection fraction (LVEF) and a resting heart rate above 70 bpm despite background guideline-directed medical therapy. Participants were randomized double blind to ivabradine titrated to a maximum of 7.5 mg twice daily or placebo and followed for a median of about 23 months. The rate of death due to heart failure was 3% with ivabradine and 5% with placebo, for a statistically significant 26% relative risk reduction favoring ivabradine.
But the drug’s main benefit was in reducing recurrent hospitalizations for heart failure, an endpoint of particular interest to health policy officials given that heart failure hospitalizations chew up a substantial proportion of the Medicare budget. Ivabradine reduced first hospitalizations for heart failure during the study period by 25%, second hospitalizations by 34%, and third hospitalizations by 29% (Eur Heart J. 2012 Nov;33[22]:2813-20).
The ACC/AHA guideline update stresses the importance of reserving ivabradine for heart failure patients whose resting heart rate exceeds 70 bpm, despite being on their maximum tolerated dose of a beta-blocker, Dr. Abraham noted.
Ivabradine is contraindicated in the setting of acute decompensated heart failure, severe liver disease, or hypotension, in patients on any of the numerous agents that strongly inhibit the enzyme cytochrome P450 3A4, and in those who have sick sinus syndrome, have sinoatrial block, or are pacemaker dependent.
Sacubitril/valsartan
Sacubitril inhibits neprilysin, an enzyme that blocks the action of endogenous vasoactive peptides including bradykinin, substance P, and natriuretic peptides, all of which counter important maladaptive mechanisms in heart failure. Sacubitril has been combined with the angiotensin receptor blocker valsartan to form the first-in-class angiotensin receptor neprilysin inhibitor, or ARNI, formerly known as LCZ696 and now marketed as Entresto.
In the pivotal double-blind PARADIGM-HF trial, 8,442 patients with heart failure with reduced ejection fraction were randomized to the ARNI at 200 mg b.i.d. or to enalapril at 10 mg b.i.d. on top of background guideline-directed medical therapy. The trial was stopped early because of evidence of overwhelming benefit: a 20% relative risk reduction in cardiovascular death and a 21% decrease in the risk of heart failure hospitalizations in the sacubitril/valsartan group, as well as significant reductions in heart failure symptoms and physical limitations (N Engl J Med. 2014 Sep 11;371[11]:993-1004).
The updated heart failure guidelines strongly recommend that patients with heart failure should be treated with either an ACE inhibitor, an angiotensin receptor blocker, or an ARNI. Further, patients who remain symptomatic on an ACE inhibitor or angiotensin receptor blocker should be switched to an ARNI; that’s a class Ib recommendation based upon the results of PARADIGM-HF.
In getting started using the ARNI, Dr. Abraham said it’s important to understand as background the selective nature of the PARADIGM-HF study design. During the single-blind run-in period of 5-8 weeks, roughly 10% of patients dropped out because they couldn’t tolerate enalapril at 10 mg b.i.d., and a similar percentage dropped out during the ARNI run-in. Thus, patients who couldn’t tolerate a low dose of an ACE inhibitor weren’t in the study. And patients capable of tolerating guideline-recommended full-dose ACE inhibitor therapy were not specifically sought for participation.
“So there are some unanswered questions about the ARNI. If you’re just getting started with this compound in treating your heart failure patients, my own feeling is you should maybe aim for the type of patient that was included in this trial: patients who could tolerate a moderate dose of an ACE inhibitor and had generally good blood pressure. That’s a great way to begin to get experience with this agent in heart failure,” the cardiologist advised.
He reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – As William T. Abraham, MD, speaks to colleagues around the country about heart failure therapy, he has noticed that the first-in-class drug ivabradine remains below the radar of most physicians.
“I’ve found that this is an agent that very few people know about, even though it’s been FDA [Food and Drug Administration] approved for about 3 years. It’s used fairly extensively in Europe because that’s where the pivotal SHIFT trial was done, but not very much in the United States,” according to Dr. Abraham, professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus.
That’s likely to change as word spreads about the May 2016 update of the American College of Cardiology/American Heart Association Guideline for the Management of Heart Failure. The update incorporated evidence-based recommendations on the use of two important new heart failure medications: ivabradine (Corlanor), which received a moderate class IIa recommendation, meaning the drug “should be considered,” and sacubitril/valsartan (Entresto), which received the strongest class I recommendation.
In the right patients, these two oral medications improve heart failure morbidity and mortality significantly beyond what’s achievable with what has been the gold standard, guideline-directed medical therapy. Dr. Abraham described how to get started using the two medications at the Annual Cardiovascular Conference at Snowmass.
Ivabradine
Ivabradine is a selective inhibitor of the sinoatrial pacemaker modulating I(f) current. It acts by slowing the sinus rate without reducing myocardial contractility.
“This agent does one thing and one thing alone: It lowers heart rate,” the cardiologist explained.
And that, he added, was sufficient to significantly reduce the risks of death due to heart failure and recurrent hospitalization for worsening heart failure in the pivotal SHIFT trial.
SHIFT included 6,505 patients with moderate to severe heart failure with reduced left ventricular ejection fraction (LVEF) and a resting heart rate above 70 bpm despite background guideline-directed medical therapy. Participants were randomized double blind to ivabradine titrated to a maximum of 7.5 mg twice daily or placebo and followed for a median of about 23 months. The rate of death due to heart failure was 3% with ivabradine and 5% with placebo, for a statistically significant 26% relative risk reduction favoring ivabradine.
But the drug’s main benefit was in reducing recurrent hospitalizations for heart failure, an endpoint of particular interest to health policy officials given that heart failure hospitalizations chew up a substantial proportion of the Medicare budget. Ivabradine reduced first hospitalizations for heart failure during the study period by 25%, second hospitalizations by 34%, and third hospitalizations by 29% (Eur Heart J. 2012 Nov;33[22]:2813-20).
The ACC/AHA guideline update stresses the importance of reserving ivabradine for heart failure patients whose resting heart rate exceeds 70 bpm, despite being on their maximum tolerated dose of a beta-blocker, Dr. Abraham noted.
Ivabradine is contraindicated in the setting of acute decompensated heart failure, severe liver disease, or hypotension, in patients on any of the numerous agents that strongly inhibit the enzyme cytochrome P450 3A4, and in those who have sick sinus syndrome, have sinoatrial block, or are pacemaker dependent.
Sacubitril/valsartan
Sacubitril inhibits neprilysin, an enzyme that blocks the action of endogenous vasoactive peptides including bradykinin, substance P, and natriuretic peptides, all of which counter important maladaptive mechanisms in heart failure. Sacubitril has been combined with the angiotensin receptor blocker valsartan to form the first-in-class angiotensin receptor neprilysin inhibitor, or ARNI, formerly known as LCZ696 and now marketed as Entresto.
In the pivotal double-blind PARADIGM-HF trial, 8,442 patients with heart failure with reduced ejection fraction were randomized to the ARNI at 200 mg b.i.d. or to enalapril at 10 mg b.i.d. on top of background guideline-directed medical therapy. The trial was stopped early because of evidence of overwhelming benefit: a 20% relative risk reduction in cardiovascular death and a 21% decrease in the risk of heart failure hospitalizations in the sacubitril/valsartan group, as well as significant reductions in heart failure symptoms and physical limitations (N Engl J Med. 2014 Sep 11;371[11]:993-1004).
The updated heart failure guidelines strongly recommend that patients with heart failure should be treated with either an ACE inhibitor, an angiotensin receptor blocker, or an ARNI. Further, patients who remain symptomatic on an ACE inhibitor or angiotensin receptor blocker should be switched to an ARNI; that’s a class Ib recommendation based upon the results of PARADIGM-HF.
In getting started using the ARNI, Dr. Abraham said it’s important to understand as background the selective nature of the PARADIGM-HF study design. During the single-blind run-in period of 5-8 weeks, roughly 10% of patients dropped out because they couldn’t tolerate enalapril at 10 mg b.i.d., and a similar percentage dropped out during the ARNI run-in. Thus, patients who couldn’t tolerate a low dose of an ACE inhibitor weren’t in the study. And patients capable of tolerating guideline-recommended full-dose ACE inhibitor therapy were not specifically sought for participation.
“So there are some unanswered questions about the ARNI. If you’re just getting started with this compound in treating your heart failure patients, my own feeling is you should maybe aim for the type of patient that was included in this trial: patients who could tolerate a moderate dose of an ACE inhibitor and had generally good blood pressure. That’s a great way to begin to get experience with this agent in heart failure,” the cardiologist advised.
He reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
The percutaneous mitral valve replacement pipe dream
SNOWMASS, COLO. – Percutaneous mitral valve replacement is unlikely to ever catch on in any way remotely approaching that of transcatheter aortic valve replacement for the treatment of aortic stenosis, Blase A. Carabello, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
“We’ve spent $2 billion looking for methods of percutaneous mitral valve replacement, and yet, I have to wonder if that makes any sense,” said Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“If repair is superior to replacement in primary MR [mitral regurgitation], which I think we all agree is true, and you don’t need to get rid of every last molecule of blood going backward across the mitral valve when you’ve got a good left ventricle, then a percutaneous replacement in primary MR would have only the niche of patients who are inoperable and whose leaflets can’t be grabbed by the MitraClip or some new percutaneous device down the road. And, in secondary MR, it doesn’t seem to matter whether you replace or repair the valve, so why not just repair it with a clip?” he argued.
Numerous nonrandomized studies have invariably demonstrated superior survival for surgical repair versus replacement in patients with primary MR.
“There’s never going to be a randomized controlled trial of repair versus replacement; there’s no equipoise there. We all believe that, in primary MR, repair is superior to replacement. There are no data anywhere to suggest the opposite. It’s essentially sacrosanct,” according to the cardiologist.
In contrast, a major randomized trial of surgical repair versus replacement has been conducted in patients with severe secondary MR. This NIH-funded study conducted by the Cardiothoracic Surgical Trials Network found no difference in survival between the two groups (N Engl J Med. 2016 Jan 28; 374[4]:344-53). That’s not a surprising result, Dr. Carabello said, since the underlying cause of this type of valve disease is a sick left ventricle. But, since surgical repair entails less morbidity than replacement – and a percutaneous repair with a leaflet-grasping device such as the MitraClip is simpler and safer than a surgical repair – it seems likely that the future treatment for secondary MR will be a percutaneous device, he said.
That future could depend upon the results of the ongoing COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy), in which the MitraClip is being studied as an alternative to surgical repair for significant secondary MR. The MitraClip, which doesn’t entail a concomitant annuloplasty, is currently approved by the Food and Drug Administration only for patients with primary, degenerative mitral regurgitation not amenable to surgical repair. But, if COAPT yields positive results, the role of the MitraClip will greatly expand.
An intriguing and poorly understood difference exists in the significance of residual mitral regurgitation following surgical repair as opposed to percutaneous MitraClip repair, Dr. Carabello observed.
“I go to the OR a lot, and I know of no surgeon [who] will leave 2+ MR behind. Most surgeons won’t leave 1+ MR behind. They’ll put the patient back on the pump to repair even mild residual MR, accepting only trace MR or zero before they leave the OR because they know that the best predictor of a failed mitral repair is the presence of residual MR in the OR,” he said.
In contrast, following successful deployment of the MitraClip most patients are left with 1-2+ MR. Yet, as was demonstrated in the 5-year results of the randomized EVEREST II trial (Endovascular Valve Edge-to-Edge Repair Study), this residual MR wasn’t a harbinger of poor outcomes long-term (J Am Coll Cardiol. 2015 Dec 29;66[25]:2844-54).
“You would have expected, with that much residual MR, there would be a perpetually increasing failure rate over time, but that didn’t happen. In Everest II, there was an early failure rate for percutaneous repair, where the MitraClip didn’t work and those patients required surgical mitral valve repair. But, after the first 6 months, the failure rate for the clip was exactly the same as the surgical failure rate, even though, with the clip, you start with more MR to begin with,” the cardiologist noted.
The MitraClip procedure is modeled after the surgical Alfieri double-orifice end-to-end stitch technique, which has been shown to have durable results when performed in conjunction with an annuloplasty ring for primary MR.
“The MitraClip essentially joins the valve in the middle the way the Alfieri stitch does, but it doesn’t appear to behave the same way. Why is that? Maybe the clip does something different than the Alfieri stitch on which it was modeled. Maybe that bar in the middle of the mitral valve does something in terms of scarring or stabilization that we don’t know about yet,” he speculated.
As for the prospects for percutaneous mitral valve replacement, Dr. Carabello said that this type of procedure “is a very difficult thing to do, and so far, has been met with a fair amount of failure. It’ll be very interesting to see what percentage of market share it gets 10 years down the road. My prediction is that, for mitral regurgitation, repair is always going to be it.”
Dr. Carabello reported serving on a data safety monitoring board for Edwards Lifesciences.
The author provides valuable insight into how the definition of “success” of a procedure can change depending on the approach to the problem. While the gold standard of open mitral valve repair is 1+ regurgitation or less, those promoting percutaneous valve replacement are willing to accept long term 1+ to 2+ regurgitation. New technology and innovation is critical in medicine, provided the results are at least equivalent or superior to the standard techniques.
The author provides valuable insight into how the definition of “success” of a procedure can change depending on the approach to the problem. While the gold standard of open mitral valve repair is 1+ regurgitation or less, those promoting percutaneous valve replacement are willing to accept long term 1+ to 2+ regurgitation. New technology and innovation is critical in medicine, provided the results are at least equivalent or superior to the standard techniques.
The author provides valuable insight into how the definition of “success” of a procedure can change depending on the approach to the problem. While the gold standard of open mitral valve repair is 1+ regurgitation or less, those promoting percutaneous valve replacement are willing to accept long term 1+ to 2+ regurgitation. New technology and innovation is critical in medicine, provided the results are at least equivalent or superior to the standard techniques.
SNOWMASS, COLO. – Percutaneous mitral valve replacement is unlikely to ever catch on in any way remotely approaching that of transcatheter aortic valve replacement for the treatment of aortic stenosis, Blase A. Carabello, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
“We’ve spent $2 billion looking for methods of percutaneous mitral valve replacement, and yet, I have to wonder if that makes any sense,” said Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“If repair is superior to replacement in primary MR [mitral regurgitation], which I think we all agree is true, and you don’t need to get rid of every last molecule of blood going backward across the mitral valve when you’ve got a good left ventricle, then a percutaneous replacement in primary MR would have only the niche of patients who are inoperable and whose leaflets can’t be grabbed by the MitraClip or some new percutaneous device down the road. And, in secondary MR, it doesn’t seem to matter whether you replace or repair the valve, so why not just repair it with a clip?” he argued.
Numerous nonrandomized studies have invariably demonstrated superior survival for surgical repair versus replacement in patients with primary MR.
“There’s never going to be a randomized controlled trial of repair versus replacement; there’s no equipoise there. We all believe that, in primary MR, repair is superior to replacement. There are no data anywhere to suggest the opposite. It’s essentially sacrosanct,” according to the cardiologist.
In contrast, a major randomized trial of surgical repair versus replacement has been conducted in patients with severe secondary MR. This NIH-funded study conducted by the Cardiothoracic Surgical Trials Network found no difference in survival between the two groups (N Engl J Med. 2016 Jan 28; 374[4]:344-53). That’s not a surprising result, Dr. Carabello said, since the underlying cause of this type of valve disease is a sick left ventricle. But, since surgical repair entails less morbidity than replacement – and a percutaneous repair with a leaflet-grasping device such as the MitraClip is simpler and safer than a surgical repair – it seems likely that the future treatment for secondary MR will be a percutaneous device, he said.
That future could depend upon the results of the ongoing COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy), in which the MitraClip is being studied as an alternative to surgical repair for significant secondary MR. The MitraClip, which doesn’t entail a concomitant annuloplasty, is currently approved by the Food and Drug Administration only for patients with primary, degenerative mitral regurgitation not amenable to surgical repair. But, if COAPT yields positive results, the role of the MitraClip will greatly expand.
An intriguing and poorly understood difference exists in the significance of residual mitral regurgitation following surgical repair as opposed to percutaneous MitraClip repair, Dr. Carabello observed.
“I go to the OR a lot, and I know of no surgeon [who] will leave 2+ MR behind. Most surgeons won’t leave 1+ MR behind. They’ll put the patient back on the pump to repair even mild residual MR, accepting only trace MR or zero before they leave the OR because they know that the best predictor of a failed mitral repair is the presence of residual MR in the OR,” he said.
In contrast, following successful deployment of the MitraClip most patients are left with 1-2+ MR. Yet, as was demonstrated in the 5-year results of the randomized EVEREST II trial (Endovascular Valve Edge-to-Edge Repair Study), this residual MR wasn’t a harbinger of poor outcomes long-term (J Am Coll Cardiol. 2015 Dec 29;66[25]:2844-54).
“You would have expected, with that much residual MR, there would be a perpetually increasing failure rate over time, but that didn’t happen. In Everest II, there was an early failure rate for percutaneous repair, where the MitraClip didn’t work and those patients required surgical mitral valve repair. But, after the first 6 months, the failure rate for the clip was exactly the same as the surgical failure rate, even though, with the clip, you start with more MR to begin with,” the cardiologist noted.
The MitraClip procedure is modeled after the surgical Alfieri double-orifice end-to-end stitch technique, which has been shown to have durable results when performed in conjunction with an annuloplasty ring for primary MR.
“The MitraClip essentially joins the valve in the middle the way the Alfieri stitch does, but it doesn’t appear to behave the same way. Why is that? Maybe the clip does something different than the Alfieri stitch on which it was modeled. Maybe that bar in the middle of the mitral valve does something in terms of scarring or stabilization that we don’t know about yet,” he speculated.
As for the prospects for percutaneous mitral valve replacement, Dr. Carabello said that this type of procedure “is a very difficult thing to do, and so far, has been met with a fair amount of failure. It’ll be very interesting to see what percentage of market share it gets 10 years down the road. My prediction is that, for mitral regurgitation, repair is always going to be it.”
Dr. Carabello reported serving on a data safety monitoring board for Edwards Lifesciences.
SNOWMASS, COLO. – Percutaneous mitral valve replacement is unlikely to ever catch on in any way remotely approaching that of transcatheter aortic valve replacement for the treatment of aortic stenosis, Blase A. Carabello, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
“We’ve spent $2 billion looking for methods of percutaneous mitral valve replacement, and yet, I have to wonder if that makes any sense,” said Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“If repair is superior to replacement in primary MR [mitral regurgitation], which I think we all agree is true, and you don’t need to get rid of every last molecule of blood going backward across the mitral valve when you’ve got a good left ventricle, then a percutaneous replacement in primary MR would have only the niche of patients who are inoperable and whose leaflets can’t be grabbed by the MitraClip or some new percutaneous device down the road. And, in secondary MR, it doesn’t seem to matter whether you replace or repair the valve, so why not just repair it with a clip?” he argued.
Numerous nonrandomized studies have invariably demonstrated superior survival for surgical repair versus replacement in patients with primary MR.
“There’s never going to be a randomized controlled trial of repair versus replacement; there’s no equipoise there. We all believe that, in primary MR, repair is superior to replacement. There are no data anywhere to suggest the opposite. It’s essentially sacrosanct,” according to the cardiologist.
In contrast, a major randomized trial of surgical repair versus replacement has been conducted in patients with severe secondary MR. This NIH-funded study conducted by the Cardiothoracic Surgical Trials Network found no difference in survival between the two groups (N Engl J Med. 2016 Jan 28; 374[4]:344-53). That’s not a surprising result, Dr. Carabello said, since the underlying cause of this type of valve disease is a sick left ventricle. But, since surgical repair entails less morbidity than replacement – and a percutaneous repair with a leaflet-grasping device such as the MitraClip is simpler and safer than a surgical repair – it seems likely that the future treatment for secondary MR will be a percutaneous device, he said.
That future could depend upon the results of the ongoing COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy), in which the MitraClip is being studied as an alternative to surgical repair for significant secondary MR. The MitraClip, which doesn’t entail a concomitant annuloplasty, is currently approved by the Food and Drug Administration only for patients with primary, degenerative mitral regurgitation not amenable to surgical repair. But, if COAPT yields positive results, the role of the MitraClip will greatly expand.
An intriguing and poorly understood difference exists in the significance of residual mitral regurgitation following surgical repair as opposed to percutaneous MitraClip repair, Dr. Carabello observed.
“I go to the OR a lot, and I know of no surgeon [who] will leave 2+ MR behind. Most surgeons won’t leave 1+ MR behind. They’ll put the patient back on the pump to repair even mild residual MR, accepting only trace MR or zero before they leave the OR because they know that the best predictor of a failed mitral repair is the presence of residual MR in the OR,” he said.
In contrast, following successful deployment of the MitraClip most patients are left with 1-2+ MR. Yet, as was demonstrated in the 5-year results of the randomized EVEREST II trial (Endovascular Valve Edge-to-Edge Repair Study), this residual MR wasn’t a harbinger of poor outcomes long-term (J Am Coll Cardiol. 2015 Dec 29;66[25]:2844-54).
“You would have expected, with that much residual MR, there would be a perpetually increasing failure rate over time, but that didn’t happen. In Everest II, there was an early failure rate for percutaneous repair, where the MitraClip didn’t work and those patients required surgical mitral valve repair. But, after the first 6 months, the failure rate for the clip was exactly the same as the surgical failure rate, even though, with the clip, you start with more MR to begin with,” the cardiologist noted.
The MitraClip procedure is modeled after the surgical Alfieri double-orifice end-to-end stitch technique, which has been shown to have durable results when performed in conjunction with an annuloplasty ring for primary MR.
“The MitraClip essentially joins the valve in the middle the way the Alfieri stitch does, but it doesn’t appear to behave the same way. Why is that? Maybe the clip does something different than the Alfieri stitch on which it was modeled. Maybe that bar in the middle of the mitral valve does something in terms of scarring or stabilization that we don’t know about yet,” he speculated.
As for the prospects for percutaneous mitral valve replacement, Dr. Carabello said that this type of procedure “is a very difficult thing to do, and so far, has been met with a fair amount of failure. It’ll be very interesting to see what percentage of market share it gets 10 years down the road. My prediction is that, for mitral regurgitation, repair is always going to be it.”
Dr. Carabello reported serving on a data safety monitoring board for Edwards Lifesciences.
Older recreational endurance athletes face sky-high AF risk
SNOWMASS, COLO. – , N. A. Mark Estes III, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I see a very large number of former collegiate or professional athletes who come to me in their 40s, 50s, and 60s having recently developed A-fib. These are mainly men who’ve been doing high-intensity endurance exercise,” said Dr. Estes, professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University in Boston.
This is an aspect of the athletic heart syndrome that has gone understudied and underappreciated, according to Dr. Estes, who asserted, “The best available evidence suggests that exercise, if excessive, is probably harmful. I know that’s heresy.”
He is coauthor of a forthcoming review on this topic to be published in the Journal of the American College of Cardiology – Electrophysiology. In it, he and his coauthors analyzed more than a half dozen published observational epidemiologic studies and concluded that the collective data show a classic J-shaped curve describes the relationship between physical activity level and risk of developing AF, but only in men. The risk is roughly 25% lower in men who regularly engage in moderate physical activity as defined in American Heart Association/American College of Cardiology guidelines, compared with that of sedentary men. But the AF risk shoots up dramatically in men who focus on intense exercise.
“As you get into the high-intensity/high-endurance end of the spectrum – typically more than 5 hours per week at greater than 80% of peak heart rate – the risk of A-fib increases up to 10-fold,” according to Dr. Estes.
“These are new data. They are important data. I think these data should impact the way we counsel people about exercise, particularly men who like to get into that high-intensity/high-endurance range,” the cardiologist continued.
This J-curve doesn’t apply to women, for reasons unclear. The analysis by Dr. Estes and his colleagues documented that women who engage in moderate physical activity have a lower risk of developing AF than do sedentary women, but unlike in men, the AF risk is lower still in women who favor high-intensity exercise.
“Maybe the explanation is in part endocrinologic differences, maybe in part due to women having smaller left atria and therefore less left atrial wall stress, less fibrosis. We really don’t know, but I think the observation, based on epidemiologic data, is valid,” he said.
Proposed multifactorial mechanisms for the increased incidence of AF in aging endurance athletes hinge in part upon basic science studies. These mechanisms include atrial inflammation and fibrosis, atrial enlargement, increased vagal tone, sympathetic nervous system stimulation, pulmonary vein triggers, genetic predisposition, and use of performance-enhancing substances.
Dr. Estes’ presentation struck a responsive chord with the audience. Numerous cardiologists rose to chime in that they, too, have encountered new-onset AF in middle-aged patients, friends, and medical colleagues who are serious cyclists, marathoners, and devotees of other forms of high-intensity endurance exercise to the tune of 10-20 hours per weekly.
“I know an electrophysiologist in his 60s who probably does 20 hours per week of spin and Cross-Fit classes and who is just now going into A-fib. How should I counsel him about this?” one audience member asked.
“You can’t tell these people to stop exercising,” Dr. Estes replied. “It’s so much a part of their identity. Their endorphin levels go down, and they feel depressed.”
For these patients he stresses what he called “the virtue of moderation.”
“If they have clinically important symptoms, many times we’ll decondition them. Often their symptoms will improve, and, in some instances, the A-fib will actually clear up and we don’t even need to go to any medical therapy,” Dr. Estes said.
His exercise prescription for deconditioning such patients is “basically nothing more than a moderate jog, a 10-minute mile. They should be able to carry on a conversation, with a peak heart rate no more than 60% of their maximum.”
If drug therapy is required, he favors rate control with beta blockers, as these patients generally don’t tolerate antiarrhythmic agents very well.
“Our threshold for AF ablation in these people is quite low because the response rate is high in paroxysmal AF in the absence of underlying structural heart disease,” he added.
Dr. Robert A. Vogel, who has been a consultant to the National Football League for a decade, commented, “I agree that you can exercise too much. These are the super-elite triathletes and so forth. A few of these folks not only get A-fib, but we’ve shown they can get accelerated atherosclerosis due to pervasive endothelial dysfunction caused by excessive athletics.”
“However, nothing here should be construed as saying exercise is bad for you. Athletes, even drug-taking cyclists and football players, actually live longer than similar nonathletes,” said Dr. Vogel, a cardiologist at the University of Colorado, Denver.
Dr. Estes was quick to agree.
“The cardiovascular benefits of exercise resoundingly overwhelm the adverse effects in that small group that experiences adverse effects,” he said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
SNOWMASS, COLO. – , N. A. Mark Estes III, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I see a very large number of former collegiate or professional athletes who come to me in their 40s, 50s, and 60s having recently developed A-fib. These are mainly men who’ve been doing high-intensity endurance exercise,” said Dr. Estes, professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University in Boston.
This is an aspect of the athletic heart syndrome that has gone understudied and underappreciated, according to Dr. Estes, who asserted, “The best available evidence suggests that exercise, if excessive, is probably harmful. I know that’s heresy.”
He is coauthor of a forthcoming review on this topic to be published in the Journal of the American College of Cardiology – Electrophysiology. In it, he and his coauthors analyzed more than a half dozen published observational epidemiologic studies and concluded that the collective data show a classic J-shaped curve describes the relationship between physical activity level and risk of developing AF, but only in men. The risk is roughly 25% lower in men who regularly engage in moderate physical activity as defined in American Heart Association/American College of Cardiology guidelines, compared with that of sedentary men. But the AF risk shoots up dramatically in men who focus on intense exercise.
“As you get into the high-intensity/high-endurance end of the spectrum – typically more than 5 hours per week at greater than 80% of peak heart rate – the risk of A-fib increases up to 10-fold,” according to Dr. Estes.
“These are new data. They are important data. I think these data should impact the way we counsel people about exercise, particularly men who like to get into that high-intensity/high-endurance range,” the cardiologist continued.
This J-curve doesn’t apply to women, for reasons unclear. The analysis by Dr. Estes and his colleagues documented that women who engage in moderate physical activity have a lower risk of developing AF than do sedentary women, but unlike in men, the AF risk is lower still in women who favor high-intensity exercise.
“Maybe the explanation is in part endocrinologic differences, maybe in part due to women having smaller left atria and therefore less left atrial wall stress, less fibrosis. We really don’t know, but I think the observation, based on epidemiologic data, is valid,” he said.
Proposed multifactorial mechanisms for the increased incidence of AF in aging endurance athletes hinge in part upon basic science studies. These mechanisms include atrial inflammation and fibrosis, atrial enlargement, increased vagal tone, sympathetic nervous system stimulation, pulmonary vein triggers, genetic predisposition, and use of performance-enhancing substances.
Dr. Estes’ presentation struck a responsive chord with the audience. Numerous cardiologists rose to chime in that they, too, have encountered new-onset AF in middle-aged patients, friends, and medical colleagues who are serious cyclists, marathoners, and devotees of other forms of high-intensity endurance exercise to the tune of 10-20 hours per weekly.
“I know an electrophysiologist in his 60s who probably does 20 hours per week of spin and Cross-Fit classes and who is just now going into A-fib. How should I counsel him about this?” one audience member asked.
“You can’t tell these people to stop exercising,” Dr. Estes replied. “It’s so much a part of their identity. Their endorphin levels go down, and they feel depressed.”
For these patients he stresses what he called “the virtue of moderation.”
“If they have clinically important symptoms, many times we’ll decondition them. Often their symptoms will improve, and, in some instances, the A-fib will actually clear up and we don’t even need to go to any medical therapy,” Dr. Estes said.
His exercise prescription for deconditioning such patients is “basically nothing more than a moderate jog, a 10-minute mile. They should be able to carry on a conversation, with a peak heart rate no more than 60% of their maximum.”
If drug therapy is required, he favors rate control with beta blockers, as these patients generally don’t tolerate antiarrhythmic agents very well.
“Our threshold for AF ablation in these people is quite low because the response rate is high in paroxysmal AF in the absence of underlying structural heart disease,” he added.
Dr. Robert A. Vogel, who has been a consultant to the National Football League for a decade, commented, “I agree that you can exercise too much. These are the super-elite triathletes and so forth. A few of these folks not only get A-fib, but we’ve shown they can get accelerated atherosclerosis due to pervasive endothelial dysfunction caused by excessive athletics.”
“However, nothing here should be construed as saying exercise is bad for you. Athletes, even drug-taking cyclists and football players, actually live longer than similar nonathletes,” said Dr. Vogel, a cardiologist at the University of Colorado, Denver.
Dr. Estes was quick to agree.
“The cardiovascular benefits of exercise resoundingly overwhelm the adverse effects in that small group that experiences adverse effects,” he said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
SNOWMASS, COLO. – , N. A. Mark Estes III, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I see a very large number of former collegiate or professional athletes who come to me in their 40s, 50s, and 60s having recently developed A-fib. These are mainly men who’ve been doing high-intensity endurance exercise,” said Dr. Estes, professor of medicine and director of the New England Cardiac Arrhythmia Center at Tufts University in Boston.
This is an aspect of the athletic heart syndrome that has gone understudied and underappreciated, according to Dr. Estes, who asserted, “The best available evidence suggests that exercise, if excessive, is probably harmful. I know that’s heresy.”
He is coauthor of a forthcoming review on this topic to be published in the Journal of the American College of Cardiology – Electrophysiology. In it, he and his coauthors analyzed more than a half dozen published observational epidemiologic studies and concluded that the collective data show a classic J-shaped curve describes the relationship between physical activity level and risk of developing AF, but only in men. The risk is roughly 25% lower in men who regularly engage in moderate physical activity as defined in American Heart Association/American College of Cardiology guidelines, compared with that of sedentary men. But the AF risk shoots up dramatically in men who focus on intense exercise.
“As you get into the high-intensity/high-endurance end of the spectrum – typically more than 5 hours per week at greater than 80% of peak heart rate – the risk of A-fib increases up to 10-fold,” according to Dr. Estes.
“These are new data. They are important data. I think these data should impact the way we counsel people about exercise, particularly men who like to get into that high-intensity/high-endurance range,” the cardiologist continued.
This J-curve doesn’t apply to women, for reasons unclear. The analysis by Dr. Estes and his colleagues documented that women who engage in moderate physical activity have a lower risk of developing AF than do sedentary women, but unlike in men, the AF risk is lower still in women who favor high-intensity exercise.
“Maybe the explanation is in part endocrinologic differences, maybe in part due to women having smaller left atria and therefore less left atrial wall stress, less fibrosis. We really don’t know, but I think the observation, based on epidemiologic data, is valid,” he said.
Proposed multifactorial mechanisms for the increased incidence of AF in aging endurance athletes hinge in part upon basic science studies. These mechanisms include atrial inflammation and fibrosis, atrial enlargement, increased vagal tone, sympathetic nervous system stimulation, pulmonary vein triggers, genetic predisposition, and use of performance-enhancing substances.
Dr. Estes’ presentation struck a responsive chord with the audience. Numerous cardiologists rose to chime in that they, too, have encountered new-onset AF in middle-aged patients, friends, and medical colleagues who are serious cyclists, marathoners, and devotees of other forms of high-intensity endurance exercise to the tune of 10-20 hours per weekly.
“I know an electrophysiologist in his 60s who probably does 20 hours per week of spin and Cross-Fit classes and who is just now going into A-fib. How should I counsel him about this?” one audience member asked.
“You can’t tell these people to stop exercising,” Dr. Estes replied. “It’s so much a part of their identity. Their endorphin levels go down, and they feel depressed.”
For these patients he stresses what he called “the virtue of moderation.”
“If they have clinically important symptoms, many times we’ll decondition them. Often their symptoms will improve, and, in some instances, the A-fib will actually clear up and we don’t even need to go to any medical therapy,” Dr. Estes said.
His exercise prescription for deconditioning such patients is “basically nothing more than a moderate jog, a 10-minute mile. They should be able to carry on a conversation, with a peak heart rate no more than 60% of their maximum.”
If drug therapy is required, he favors rate control with beta blockers, as these patients generally don’t tolerate antiarrhythmic agents very well.
“Our threshold for AF ablation in these people is quite low because the response rate is high in paroxysmal AF in the absence of underlying structural heart disease,” he added.
Dr. Robert A. Vogel, who has been a consultant to the National Football League for a decade, commented, “I agree that you can exercise too much. These are the super-elite triathletes and so forth. A few of these folks not only get A-fib, but we’ve shown they can get accelerated atherosclerosis due to pervasive endothelial dysfunction caused by excessive athletics.”
“However, nothing here should be construed as saying exercise is bad for you. Athletes, even drug-taking cyclists and football players, actually live longer than similar nonathletes,” said Dr. Vogel, a cardiologist at the University of Colorado, Denver.
Dr. Estes was quick to agree.
“The cardiovascular benefits of exercise resoundingly overwhelm the adverse effects in that small group that experiences adverse effects,” he said.
Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Prediction: LVADs will rule end-stage heart failure
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.
declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.
That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.
Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.
Here’s what Dr. Woo sees as the future of MCS:
Minimally invasive implantation
At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.
“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.
Concomitant valvular surgery
At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.
Enhanced right ventricular management
Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.
Adjunctive biologic therapies
Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).
The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.
These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.
Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.
New technologies
The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.
Dr. Woo reported having no financial conflicts.
bjancin@frontlinemedcom.com
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Big changes ahead in heart failure management
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
SNOWMASS, COLO. – Advances in remote telemedical management show enormous promise as a means of preventing costly heart failure hospitalizations, William T. Abraham, MD, said at the Annual Cardiovascular Conference at Snowmass.
He characterized the decades-old conventional approach to heart failure management as a reactive strategy focused on making medication adjustments based upon weight changes and worsening signs and symptoms. But these physiologic markers of acute decompensation aren’t actionable; that is, they don’t occur until it’s too late to successfully intervene to prevent hospitalization.
It’s now clear that objective, measurable changes in intracardiac and pulmonary artery pressures as well as increases in lung fluid volume precede symptomatic decompensation episodes by several weeks. These early harbingers are reliably detectable by telemedical monitoring via small implantable pressure sensors or, noninvasively, using wearable sensors embedded in a vest.
“By moving upstream, we hope to develop a more proactive preventive approach to managing heart failure patients so that we can implement a medical intervention during this presymptomatic phase of worsening heart failure and avert a heart failure hospitalization,” the cardiologist explained.
That has already been demonstrated in several studies in which remote physicians checked the home monitoring data daily and promptly increased the dose of diuretics when pressure readings or lung fluid volume climbed above normal: The elevated readings quickly retreated and heart failure hospitalizations occurred much less frequently than with conventional management.
“Well-structured outpatient care could reduce the need for hospital admission, facilitate early intervention, prevent crisis management, and avoid complications or disease management in these patients,” Dr. Abraham observed.
Finding best telemedicine options
But this high-tech patient management strategy is not quite ready for prime time use in daily clinical practice.
“We’re still sorting through this field and trying to figure out the best telemedicine options,” according to Dr. Abraham.
He cited several recent large, well-conducted randomized trials that have persuasively shown that there’s no point in applying home telemedicine in order to quickly respond to changes in a heart failure patient’s blood pressure, weight, and symptom status.
“The horse is already out of the barn at that point in time,” according to the cardiologist.
For example, the BEAT-HF (Better Effectiveness After Transition–Heart Failure) trial included 1,437 patients hospitalized for heart failure at eight California academic medical centers who were randomized to usual care or an intervention that combined health-coaching telephone calls and protocols for physician or nurse response to daily telemetric data on patient blood pressure, symptoms, heart rate, weight, and symptoms. The intervention turned out to have absolutely no effect on the 180-day rate of readmissions, which was roughly 50% in both groups (JAMA Intern Med. 2016 Mar;176[3]:310-8).
The PCDM (Patient-Centered Disease Management) trial was a multicenter Veterans Affairs study that randomized heart failure patients to usual care or a comprehensive intervention involving collaborative care by a cardiologist, psychiatrist, primary care physician, and nurse coordinator; screening and treatment for depression; and home telemonitoring of heart failure decompensation symptoms. The multifaceted intervention had no effect on the 1-year readmission rate (JAMA Intern Med. 2015 May;175[5]:725-32).
“To date, I would challenge you to find any adequately powered randomized, controlled trial in heart failure disease management that demonstrates that the way we’ve been doing things really keeps heart failure patients out of the hospital. So, it is time for a paradigm shift and some new technologies in our armamentarium,” Dr. Abraham said.
CardioMEMS system
Several remote telemedical management systems for heart failure, which measure early preclinical harbingers of acute decompensation, have received Food and Drug Administration approval. Many more are in development. Dr. Abraham highlighted two approved systems for which he was a coinvestigator in clinical trials.
The CardioMEMS system uses a pressure sensor the size of a small paper clip that is placed in a branch of the pulmonary artery, where it readily becomes endothelialized. Device implantation can be carried out by any cardiologist who can perform a right heart catheterization, be it an electrophysiologist, interventionalist, heart failure specialist, or general cardiologist. It takes only about an additional 7 minutes to deploy the sensor following a standard diagnostic right heart catheterization. The system doesn’t use a battery and has no moving parts.
“Now, with more than 10 years experience, we have yet to see a sensor failure. It’s a highly reliable system,” according to the cardiologist.
Once a day the patient lies down, pushes a button, and the sensor is simultaneously powered up while the data on pulmonary artery pressure waveforms and systolic and diastolic pressures is extracted using radiofrequency energy.
In the randomized, multicenter, controlled, single-blind CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial, Dr. Abraham and coinvestigators demonstrated that pulmonary artery pressure-guided heart failure management reduced the rate of heart failure hospitalizations in the CardioMEMS group by 33% during the first 18 months of the trial and by 48% in the subsequent 13 months (Lancet. 2016 Jan 30;387[10017]:453-61).
“It’s important to note that the results were positive in diastolic as well as systolic heart failure. Patients with a baseline left ventricular ejection fraction of 40% or more saw a 50% reduction in the risk of heart failure hospitalizations, and those with an LVEF of 50% or more saw a 70% reduction,” Dr. Abraham said.
Other implantable hemodynamic monitors
Numerous other implantable pressure sensors are in development for management of heart failure, including other pulmonary artery pressure sensors as well as left atrial pressure monitors.
“You’re going to hear a lot more about this field of implantable hemodynamic monitors in the future,” the cardiologist predicted.
Dr. Abraham was also a coinvestigator in an observational study of a wearable sensor based upon radar technology developed for the military and subsequently applied to rescue searches through rubble for earthquake survivors. This remote dielectric sensing (ReDS) technology has been miniaturized, with the sensors embedded in an FDA-approved vest. The heart failure patient dons the SensiVest for 90 seconds once per day for measurement of the absolute amount of fluid in the lungs. The data is automatically transmitted to a secured site in the cloud, where the physician can review the results and adjust medications in response to early evidence of fluid buildup.
“The normal lung is composed of 20%-35% fluid. So when that fluid content is elevated, patients with heart failure have wet lungs and they’re decompensating. You increase their diuretics to bring it back down into normal range,” he explained.
In the observational study, conducted in Israel, hospital readmission rates were reduced by 87% through the use of ReDS-guided patient management using the system marketed by Sensible Medical Innovations. Dr. Abraham and his coinvestigators are now seeking to confirm those results in the prospective, multicenter, randomized, controlled U.S. SMILE study.
Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Familial hypercholesterolemia: Look for it!
SNOWMASS, COLO. – Familial hypercholesterolemia (FH), the most common genetic cause of premature atherosclerotic cardiovascular disease, affects an estimated 1 in 250 Americans. It doesn’t help that physicians are doing a terrible job of finding and treating them, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
Indeed, it’s estimated that U.S. physicians diagnose fewer than 1% of affected individuals, as compared with a world’s-best 71% rate in the Netherlands, 43% in Norway, 13% in Sweden, and 12% in the United Kingdom (Eur Heart J. 2013 Dec 1;34[45]:3478-90a).
“You all have patients with FH in your practices. You have the parents, who already have atherosclerotic cardiovascular disease, but the kids need to be identified as well. Nothing is as gratifying as preventing disease in someone who would suffer a stroke or MI in the future,” the cardiologist continued.
FH is present in 7.5% of men and fully 11.1% of women with coronary heart disease (CHD), according to an analysis of more than 7,000 CHD patients in the EUROASPIRE IV study (Atherosclerosis. 2015 Jul;241[1]:169-75). Swiss investigators have shown, in a prospective study of 4,534 patients with acute coronary syndrome, that those who have FH are at significantly greater 1-year risk of recurrent fatal and nonfatal coronary events (Circulation. 2016 Sep 6;134[10]:698-709).
“You’re going to do worse after an MI if you have FH. These are very-high-risk folks. We need to find them because treatment is effective,” Dr. Vogel emphasized.
Three different sets of diagnostic criteria are available for FH: the Dutch Lipid Clinic Network diagnostic criteria, the Simon Broome criteria, and most recently, the American Heart Association criteria (Circulation. 2015 Dec 1;132[22]:2167-92).
There are common themes among the three sets of diagnostic criteria: Think FH when you encounter an LDL cholesterol level greater than 190 mg/dL in a patient not on statin therapy or more than 130 mg/dL on statin therapy, a personal or family history of premature atherosclerotic cardiovascular disease, or a patient with the characteristic findings of FH on physical examination.
These characteristic physical findings are xanthelasmas, corneal arcus, tuberous xanthomas, and Achilles tendon xanthomas, which Dr. Vogel called “the sine qua non of FH.”
The importance of tendon xanthomas as a manifestation of FH is vividly illustrated in the Dutch diagnostic criteria. Under the Dutch points-based scheme, various numbers of points are given for LDL level; a personal or family history of premature CAD, peripheral vascular disease, or stroke; positive physical findings; and a genetic test positive for a functional mutation in the LDL receptor gene. “Definite FH” requires a total of more than eight points, and a finding of tendon xanthomas alone provides six of them.
Tendon xanthomas are not only a key diagnostic feature, they are also important prognostically. They indicate that a patient is going to do relatively worse, independent of LDL level or LDL receptor gene mutation status (Arterioscler Thromb Vasc Biol. 2005 Sep;25[9]:1960-5).
A genetic test isn’t needed most of the time to diagnose FH, but it’s nevertheless helpful because it provides specific information about the patient’s LDL receptor status. A patient with a receptor-negative mutation in the LDL receptor gene is going to be much less responsive to maximum-intensity statin therapy than if defective LDL receptors are present.
Another test well worth ordering in a patient with FH is a lipoprotein(a) measurement. As shown in the prospective SAFEHEART trial (Spanish Familial Hypercholesterolemia Cohort Study), lipoprotein(a) is an independent predictor of cardiovascular disease in both men and women with FH. The risk is highest in those with lipoprotein(a) above 50 mg/dL – a normal level is below 30 mg/dL – who carry a null mutation in the LDL receptor gene (J Am Coll Cardiol. 2014 May 20;63[19]:1982-9).
Dr. Vogel reported serving as U.S. national coordinator for the ongoing ODYSSEY trial of the PCSK9 inhibitor alirocumab for cardiovascular risk reduction.
SNOWMASS, COLO. – Familial hypercholesterolemia (FH), the most common genetic cause of premature atherosclerotic cardiovascular disease, affects an estimated 1 in 250 Americans. It doesn’t help that physicians are doing a terrible job of finding and treating them, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
Indeed, it’s estimated that U.S. physicians diagnose fewer than 1% of affected individuals, as compared with a world’s-best 71% rate in the Netherlands, 43% in Norway, 13% in Sweden, and 12% in the United Kingdom (Eur Heart J. 2013 Dec 1;34[45]:3478-90a).
“You all have patients with FH in your practices. You have the parents, who already have atherosclerotic cardiovascular disease, but the kids need to be identified as well. Nothing is as gratifying as preventing disease in someone who would suffer a stroke or MI in the future,” the cardiologist continued.
FH is present in 7.5% of men and fully 11.1% of women with coronary heart disease (CHD), according to an analysis of more than 7,000 CHD patients in the EUROASPIRE IV study (Atherosclerosis. 2015 Jul;241[1]:169-75). Swiss investigators have shown, in a prospective study of 4,534 patients with acute coronary syndrome, that those who have FH are at significantly greater 1-year risk of recurrent fatal and nonfatal coronary events (Circulation. 2016 Sep 6;134[10]:698-709).
“You’re going to do worse after an MI if you have FH. These are very-high-risk folks. We need to find them because treatment is effective,” Dr. Vogel emphasized.
Three different sets of diagnostic criteria are available for FH: the Dutch Lipid Clinic Network diagnostic criteria, the Simon Broome criteria, and most recently, the American Heart Association criteria (Circulation. 2015 Dec 1;132[22]:2167-92).
There are common themes among the three sets of diagnostic criteria: Think FH when you encounter an LDL cholesterol level greater than 190 mg/dL in a patient not on statin therapy or more than 130 mg/dL on statin therapy, a personal or family history of premature atherosclerotic cardiovascular disease, or a patient with the characteristic findings of FH on physical examination.
These characteristic physical findings are xanthelasmas, corneal arcus, tuberous xanthomas, and Achilles tendon xanthomas, which Dr. Vogel called “the sine qua non of FH.”
The importance of tendon xanthomas as a manifestation of FH is vividly illustrated in the Dutch diagnostic criteria. Under the Dutch points-based scheme, various numbers of points are given for LDL level; a personal or family history of premature CAD, peripheral vascular disease, or stroke; positive physical findings; and a genetic test positive for a functional mutation in the LDL receptor gene. “Definite FH” requires a total of more than eight points, and a finding of tendon xanthomas alone provides six of them.
Tendon xanthomas are not only a key diagnostic feature, they are also important prognostically. They indicate that a patient is going to do relatively worse, independent of LDL level or LDL receptor gene mutation status (Arterioscler Thromb Vasc Biol. 2005 Sep;25[9]:1960-5).
A genetic test isn’t needed most of the time to diagnose FH, but it’s nevertheless helpful because it provides specific information about the patient’s LDL receptor status. A patient with a receptor-negative mutation in the LDL receptor gene is going to be much less responsive to maximum-intensity statin therapy than if defective LDL receptors are present.
Another test well worth ordering in a patient with FH is a lipoprotein(a) measurement. As shown in the prospective SAFEHEART trial (Spanish Familial Hypercholesterolemia Cohort Study), lipoprotein(a) is an independent predictor of cardiovascular disease in both men and women with FH. The risk is highest in those with lipoprotein(a) above 50 mg/dL – a normal level is below 30 mg/dL – who carry a null mutation in the LDL receptor gene (J Am Coll Cardiol. 2014 May 20;63[19]:1982-9).
Dr. Vogel reported serving as U.S. national coordinator for the ongoing ODYSSEY trial of the PCSK9 inhibitor alirocumab for cardiovascular risk reduction.
SNOWMASS, COLO. – Familial hypercholesterolemia (FH), the most common genetic cause of premature atherosclerotic cardiovascular disease, affects an estimated 1 in 250 Americans. It doesn’t help that physicians are doing a terrible job of finding and treating them, Robert A. Vogel, MD, said at the Annual Cardiovascular Conference at Snowmass.
Indeed, it’s estimated that U.S. physicians diagnose fewer than 1% of affected individuals, as compared with a world’s-best 71% rate in the Netherlands, 43% in Norway, 13% in Sweden, and 12% in the United Kingdom (Eur Heart J. 2013 Dec 1;34[45]:3478-90a).
“You all have patients with FH in your practices. You have the parents, who already have atherosclerotic cardiovascular disease, but the kids need to be identified as well. Nothing is as gratifying as preventing disease in someone who would suffer a stroke or MI in the future,” the cardiologist continued.
FH is present in 7.5% of men and fully 11.1% of women with coronary heart disease (CHD), according to an analysis of more than 7,000 CHD patients in the EUROASPIRE IV study (Atherosclerosis. 2015 Jul;241[1]:169-75). Swiss investigators have shown, in a prospective study of 4,534 patients with acute coronary syndrome, that those who have FH are at significantly greater 1-year risk of recurrent fatal and nonfatal coronary events (Circulation. 2016 Sep 6;134[10]:698-709).
“You’re going to do worse after an MI if you have FH. These are very-high-risk folks. We need to find them because treatment is effective,” Dr. Vogel emphasized.
Three different sets of diagnostic criteria are available for FH: the Dutch Lipid Clinic Network diagnostic criteria, the Simon Broome criteria, and most recently, the American Heart Association criteria (Circulation. 2015 Dec 1;132[22]:2167-92).
There are common themes among the three sets of diagnostic criteria: Think FH when you encounter an LDL cholesterol level greater than 190 mg/dL in a patient not on statin therapy or more than 130 mg/dL on statin therapy, a personal or family history of premature atherosclerotic cardiovascular disease, or a patient with the characteristic findings of FH on physical examination.
These characteristic physical findings are xanthelasmas, corneal arcus, tuberous xanthomas, and Achilles tendon xanthomas, which Dr. Vogel called “the sine qua non of FH.”
The importance of tendon xanthomas as a manifestation of FH is vividly illustrated in the Dutch diagnostic criteria. Under the Dutch points-based scheme, various numbers of points are given for LDL level; a personal or family history of premature CAD, peripheral vascular disease, or stroke; positive physical findings; and a genetic test positive for a functional mutation in the LDL receptor gene. “Definite FH” requires a total of more than eight points, and a finding of tendon xanthomas alone provides six of them.
Tendon xanthomas are not only a key diagnostic feature, they are also important prognostically. They indicate that a patient is going to do relatively worse, independent of LDL level or LDL receptor gene mutation status (Arterioscler Thromb Vasc Biol. 2005 Sep;25[9]:1960-5).
A genetic test isn’t needed most of the time to diagnose FH, but it’s nevertheless helpful because it provides specific information about the patient’s LDL receptor status. A patient with a receptor-negative mutation in the LDL receptor gene is going to be much less responsive to maximum-intensity statin therapy than if defective LDL receptors are present.
Another test well worth ordering in a patient with FH is a lipoprotein(a) measurement. As shown in the prospective SAFEHEART trial (Spanish Familial Hypercholesterolemia Cohort Study), lipoprotein(a) is an independent predictor of cardiovascular disease in both men and women with FH. The risk is highest in those with lipoprotein(a) above 50 mg/dL – a normal level is below 30 mg/dL – who carry a null mutation in the LDL receptor gene (J Am Coll Cardiol. 2014 May 20;63[19]:1982-9).
Dr. Vogel reported serving as U.S. national coordinator for the ongoing ODYSSEY trial of the PCSK9 inhibitor alirocumab for cardiovascular risk reduction.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Consider ultraslow thrombolysis for mechanical valve thrombosis
SNOWMASS, COLO. – Ultraslow infusion of a very-low-dose thrombolytic agent for treatment of mechanical prosthetic valve thrombosis appears to be as effective as surgery – the former first-line therapy – and sports a far lower stroke risk, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I’m not saying you have to use this, but I think it’s reasonable to consider it, especially if the patient is at high risk for surgery and low risk for thrombolysis,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn. 
He added that he and his Mayo colleagues have begun using the novel therapy and are favorably impressed with the resultant complete normalization of valve gradients and low complication rate.
Dr. Nishimura was cochair of the writing committee for the current American College of Cardiology/American Heart Association guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643). Those guidelines state that emergency surgery is the treatment of choice for thrombosis of a left-sided mechanical heart valve. That strong recommendation was based on a dozen nonrandomized studies reported prior to 2013 which showed a 95% success rate with surgery compared with 75% with conventional large-bolus thrombolytic therapy, a high 10%-12% mortality with either form of therapy, and a stroke risk of 12%-14% with thrombolytic therapy, substantially higher than for surgery.
Since release of the ACC/AHA guidelines, however, there’s been an important new development: Three groups outside of the United States have pioneered ultraslow thrombolytic therapy for mechanical prosthetic valve thrombosis. The supporting evidence comes from cohort studies, with no randomized trials done to date. But the collective reported experience from these three research teams shows a 90%-95% success rate – comparable to surgery – along with stroke and mortality rates in the low single digits.
The Turkish group waits until the patient’s international normalized ratio (INR) is below 2.5, then administers 25 mg of tissue plasminogen activator guided by transesophageal echocardiography (TEE) over 25 hours.
“We traditionally give 90 mg over 1 hour, so this is very, very slow therapy,” Dr. Nishimura observed.
After the 24-hour infusion, TEE is repeated. If imaging shows the clot is not resolved, another 25 mg of tissue plasminogen activator is given over 24 hours. This process is repeated for up to 8 days as needed (Am Heart J. 2015 Aug;170[2]:409-18).
Dr. Nishimura advised reserving ultraslow thrombolytic therapy for patients who are hemodynamically stable; this treatment takes a while to work, so patients in severe heart failure should be sent straight away to surgery. The novel therapy is best suited for patients with recent-onset mechanical valve thrombosis, a low INR, TEE evidence that the clot isn’t huge, and/or when surgical expertise isn’t readily available.
Before you can treat a prosthetic mechanical valve thrombosis, however, you have to make the diagnosis. Here’s what Dr. Nishimura recommends: First, suspect the condition on the basis of clinical symptoms of heart failure and dull, muffled S1 and S2 sounds on auscultation, especially in a patient who presents with a low INR.
Next, prove that obstruction is present via Doppler echocardiographic evidence of an abnormal gradient across the mechanical valve.
Finally, determine if the mechanical valve shows abnormal disc motion with sticking leaflets. TEE is excellent for visualizing a mechanical mitral valve but isn’t helpful if it’s a mechanical aortic valve.
“Old-fashioned fluoroscopy is the best approach for looking at leaflet motion in the atrial valve and mitral valve. We’ve got 3-D cine now that provides beautiful images, but if you can get the same information with a quick fluoroscopy, go with the fluoroscopy,” the cardiologist suggested.
He reported having no financial conflicts of interest.
SNOWMASS, COLO. – Ultraslow infusion of a very-low-dose thrombolytic agent for treatment of mechanical prosthetic valve thrombosis appears to be as effective as surgery – the former first-line therapy – and sports a far lower stroke risk, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I’m not saying you have to use this, but I think it’s reasonable to consider it, especially if the patient is at high risk for surgery and low risk for thrombolysis,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
He added that he and his Mayo colleagues have begun using the novel therapy and are favorably impressed with the resultant complete normalization of valve gradients and low complication rate.
Dr. Nishimura was cochair of the writing committee for the current American College of Cardiology/American Heart Association guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643). Those guidelines state that emergency surgery is the treatment of choice for thrombosis of a left-sided mechanical heart valve. That strong recommendation was based on a dozen nonrandomized studies reported prior to 2013 which showed a 95% success rate with surgery compared with 75% with conventional large-bolus thrombolytic therapy, a high 10%-12% mortality with either form of therapy, and a stroke risk of 12%-14% with thrombolytic therapy, substantially higher than for surgery.
Since release of the ACC/AHA guidelines, however, there’s been an important new development: Three groups outside of the United States have pioneered ultraslow thrombolytic therapy for mechanical prosthetic valve thrombosis. The supporting evidence comes from cohort studies, with no randomized trials done to date. But the collective reported experience from these three research teams shows a 90%-95% success rate – comparable to surgery – along with stroke and mortality rates in the low single digits.
The Turkish group waits until the patient’s international normalized ratio (INR) is below 2.5, then administers 25 mg of tissue plasminogen activator guided by transesophageal echocardiography (TEE) over 25 hours.
“We traditionally give 90 mg over 1 hour, so this is very, very slow therapy,” Dr. Nishimura observed.
After the 24-hour infusion, TEE is repeated. If imaging shows the clot is not resolved, another 25 mg of tissue plasminogen activator is given over 24 hours. This process is repeated for up to 8 days as needed (Am Heart J. 2015 Aug;170[2]:409-18).
Dr. Nishimura advised reserving ultraslow thrombolytic therapy for patients who are hemodynamically stable; this treatment takes a while to work, so patients in severe heart failure should be sent straight away to surgery. The novel therapy is best suited for patients with recent-onset mechanical valve thrombosis, a low INR, TEE evidence that the clot isn’t huge, and/or when surgical expertise isn’t readily available.
Before you can treat a prosthetic mechanical valve thrombosis, however, you have to make the diagnosis. Here’s what Dr. Nishimura recommends: First, suspect the condition on the basis of clinical symptoms of heart failure and dull, muffled S1 and S2 sounds on auscultation, especially in a patient who presents with a low INR.
Next, prove that obstruction is present via Doppler echocardiographic evidence of an abnormal gradient across the mechanical valve.
Finally, determine if the mechanical valve shows abnormal disc motion with sticking leaflets. TEE is excellent for visualizing a mechanical mitral valve but isn’t helpful if it’s a mechanical aortic valve.
“Old-fashioned fluoroscopy is the best approach for looking at leaflet motion in the atrial valve and mitral valve. We’ve got 3-D cine now that provides beautiful images, but if you can get the same information with a quick fluoroscopy, go with the fluoroscopy,” the cardiologist suggested.
He reported having no financial conflicts of interest.
SNOWMASS, COLO. – Ultraslow infusion of a very-low-dose thrombolytic agent for treatment of mechanical prosthetic valve thrombosis appears to be as effective as surgery – the former first-line therapy – and sports a far lower stroke risk, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“I’m not saying you have to use this, but I think it’s reasonable to consider it, especially if the patient is at high risk for surgery and low risk for thrombolysis,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
He added that he and his Mayo colleagues have begun using the novel therapy and are favorably impressed with the resultant complete normalization of valve gradients and low complication rate.
Dr. Nishimura was cochair of the writing committee for the current American College of Cardiology/American Heart Association guidelines for management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643). Those guidelines state that emergency surgery is the treatment of choice for thrombosis of a left-sided mechanical heart valve. That strong recommendation was based on a dozen nonrandomized studies reported prior to 2013 which showed a 95% success rate with surgery compared with 75% with conventional large-bolus thrombolytic therapy, a high 10%-12% mortality with either form of therapy, and a stroke risk of 12%-14% with thrombolytic therapy, substantially higher than for surgery.
Since release of the ACC/AHA guidelines, however, there’s been an important new development: Three groups outside of the United States have pioneered ultraslow thrombolytic therapy for mechanical prosthetic valve thrombosis. The supporting evidence comes from cohort studies, with no randomized trials done to date. But the collective reported experience from these three research teams shows a 90%-95% success rate – comparable to surgery – along with stroke and mortality rates in the low single digits.
The Turkish group waits until the patient’s international normalized ratio (INR) is below 2.5, then administers 25 mg of tissue plasminogen activator guided by transesophageal echocardiography (TEE) over 25 hours.
“We traditionally give 90 mg over 1 hour, so this is very, very slow therapy,” Dr. Nishimura observed.
After the 24-hour infusion, TEE is repeated. If imaging shows the clot is not resolved, another 25 mg of tissue plasminogen activator is given over 24 hours. This process is repeated for up to 8 days as needed (Am Heart J. 2015 Aug;170[2]:409-18).
Dr. Nishimura advised reserving ultraslow thrombolytic therapy for patients who are hemodynamically stable; this treatment takes a while to work, so patients in severe heart failure should be sent straight away to surgery. The novel therapy is best suited for patients with recent-onset mechanical valve thrombosis, a low INR, TEE evidence that the clot isn’t huge, and/or when surgical expertise isn’t readily available.
Before you can treat a prosthetic mechanical valve thrombosis, however, you have to make the diagnosis. Here’s what Dr. Nishimura recommends: First, suspect the condition on the basis of clinical symptoms of heart failure and dull, muffled S1 and S2 sounds on auscultation, especially in a patient who presents with a low INR.
Next, prove that obstruction is present via Doppler echocardiographic evidence of an abnormal gradient across the mechanical valve.
Finally, determine if the mechanical valve shows abnormal disc motion with sticking leaflets. TEE is excellent for visualizing a mechanical mitral valve but isn’t helpful if it’s a mechanical aortic valve.
“Old-fashioned fluoroscopy is the best approach for looking at leaflet motion in the atrial valve and mitral valve. We’ve got 3-D cine now that provides beautiful images, but if you can get the same information with a quick fluoroscopy, go with the fluoroscopy,” the cardiologist suggested.
He reported having no financial conflicts of interest.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
The two faces of mitral regurgitation
SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.
“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“On the other hand, if you fix the valve, you fix the disease,” he said.
In contrast, in secondary MR, the dysfunctional valve is a result of the ventricular problem, not its cause.
“In secondary MR, it’s the ventricle that made the valve sick. It’s the regional wall motion abnormalities, the displacement of the papillary muscles, and the dilation of the mitral annulus that pulls the mitral valve apart and prevents it from coapting,” he explained.
Dr. Carabello, who was on the writing committee for the current American College of Cardiology/American Heart Association guidelines on management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643), highlighted other key distinctions between the two diseases.
Primary MR
“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.
The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.
Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.
“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.
It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.
“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.
The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.
“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.
He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).
The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.
Secondary MR
Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.
“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.
In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).
“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.
He reported serving on a data safety monitoring board for Edwards Lifesciences.
SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.
“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“On the other hand, if you fix the valve, you fix the disease,” he said.
In contrast, in secondary MR, the dysfunctional valve is a result of the ventricular problem, not its cause.
“In secondary MR, it’s the ventricle that made the valve sick. It’s the regional wall motion abnormalities, the displacement of the papillary muscles, and the dilation of the mitral annulus that pulls the mitral valve apart and prevents it from coapting,” he explained.
Dr. Carabello, who was on the writing committee for the current American College of Cardiology/American Heart Association guidelines on management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643), highlighted other key distinctions between the two diseases.
Primary MR
“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.
The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.
Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.
“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.
It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.
“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.
The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.
“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.
He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).
The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.
Secondary MR
Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.
“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.
In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).
“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.
He reported serving on a data safety monitoring board for Edwards Lifesciences.
SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.
“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.
“On the other hand, if you fix the valve, you fix the disease,” he said.
In contrast, in secondary MR, the dysfunctional valve is a result of the ventricular problem, not its cause.
“In secondary MR, it’s the ventricle that made the valve sick. It’s the regional wall motion abnormalities, the displacement of the papillary muscles, and the dilation of the mitral annulus that pulls the mitral valve apart and prevents it from coapting,” he explained.
Dr. Carabello, who was on the writing committee for the current American College of Cardiology/American Heart Association guidelines on management of valvular heart disease (Circulation. 2014 Jun 10;129[23]:e521-643), highlighted other key distinctions between the two diseases.
Primary MR
“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.
The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.
Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.
“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.
It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.
“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.
The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.
“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.
He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).
The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.
Secondary MR
Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.
“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.
In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).
“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.
He reported serving on a data safety monitoring board for Edwards Lifesciences.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
