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What 2019’s top five CAD trials tell us
SNOWMASS, COLO. – A repeated theme threading through much of one prominent interventional cardiologist’s personal list of the top five coronary artery disease (CAD) trials of the past year is that aspirin is very often more trouble than it’s worth.
“For some years I’ve been concerned that the only thing that aspirin does [in patients after percutaneous coronary intervention] is increase your risk of bleeding. It doesn’t really provide any additional ischemic protection,” Malcolm R. Bell, MBBS, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“I’ll remind you that, when we go back to the early stent days, observed Dr. Bell, professor of medicine and vice chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.
Here are the key takeaway messages from his five most important randomized trials in CAD during the last year.
AUGUSTUS
For years, cardiologists have grappled with how to best manage high-cardiovascular-risk patients with atrial fibrillation who seem like they might benefit from triple-antithrombotic therapy. AUGUSTUS supplied the answer: Don’t do it. Skip the aspirin and turn instead to a P2Y12 inhibitor plus a non–vitamin K antagonist oral anticoagulant (NOAC), rather than warfarin.
“I would like you to think of triple therapy as a triple threat. That’s really what triple therapy is all about”– a three-pronged threat to patient safety, Dr. Bell commented.
In AUGUSTUS, 4,614 patients with atrial fibrillation and CAD with an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) in 33 countries were placed on a P2Y12 inhibitor – most often clopidogrel – and randomized double blind to either apixaban (Eliquis) or warfarin, and further to aspirin or placebo, for 6 months of antithrombotic therapy. The strategy of a P2Y12 inhibitor and apixaban without aspirin was the clear winner, resulting in significantly less major bleeding, mortality, and hospitalizations than treatment with a P2Y12 inhibitor and warfarin, with or without aspirin. Most importantly, ischemic event rates didn’t differ between the apixaban and warfarin groups. And patients randomized to aspirin had rates of ischemic events and death or hospitalization similar to placebo-treated controls, meaning aspirin accomplished nothing (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
Dr. Bell noted that a meta-analysis of AUGUSTUS and three smaller randomized trials including more than 10,000 AUGUSTUS-type patients with atrial fibrillation concluded that a treatment strategy utilizing a NOAC and a P2Y12 inhibitor resulted in less bleeding than warfarin plus DAPT, and at no cost in terms of excess ischemic events. Moreover, regimens without aspirin resulted in less intracranial and other major bleeding without any difference in major adverse cardiovascular events (JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1880).
A key message of these four trials is that a NOAC is preferable to warfarin, so much so that, in high-risk patients who are already on warfarin, it’s worth considering a switch to a NOAC.
“And we should really be avoiding DAPT,” Dr. Bell added.
How soon after an ACS and/or PCI should patients with atrial fibrillation stop taking aspirin?
“In AUGUSTUS, randomization occurred at a median of 6 days, so we know that half the patients stopped their aspirin by then. In our own practice, we’re just dropping the aspirin for the most part before the patient leaves the hospital. I think if you leave them with instructions to stop the aspirin in a week’s time or a month’s time it just leads to confusion. And we should also remember that half of the major bleeding after PCI or ACS happens in the first 30 days, so it doesn’t make a lot of sense to say that we should continue it for a month and then drop it,” according to the cardiologist.
SMART-CHOICE and STOPDAPT-2
These two large multicenter studies demonstrate that DAPT can safely be stopped early if needed. SMART-CHOICE from South Korea and STOPDAPT-2 from Japan each randomized roughly 3,000 patients undergoing PCI to 12 months of DAPT or to DAPT for only 3 months or 1 month, respectively, at which point the aspirin was dropped and patients in the abbreviated DAPT arm continued on P2Y12 inhibitor monotherapy, mostly clopidogrel, for the remainder of the 12 months. In the Japanese STOPDAPT-2 trial, 1 month of DAPT proved superior to 12 months of DAPT for the primary composite endpoint of cardiovascular death, MI, stroke, definite stent thrombosis, or major or minor bleeding at 12 months (JAMA. 2019 Jun 25;321[24]:2414-27). In the South Korean SMART-CHOICE trial, 3 months of DAPT was noninferior to 12 months for major adverse cardiac and cerebrovascular events, and superior in terms of bleeding risk (JAMA. 2019 Jun 25;321[24]:2428-37). Of note, roughly half of patients in the two trials were lower-risk individuals undergoing PCI for stable angina.
Dr. Bell noted that, while the TWILIGHT trial (Ticagrelor With or Without Aspirin in High-Risk Patients After PCI) didn’t make his top-five list, it certainly fits well with the two East Asian studies. The TWILIGHT investigators randomized more than 7,000 patients to 12 months of DAPT or discontinuation of aspirin after 3 months. The result: a lower incidence of clinically relevant bleeding with ticagrelor monotherapy, and with no increased risk of death, MI, or stroke, compared with 12 months of DAPT (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
“Again, I would just question what the added value of aspirin is here,” Dr. Bell commented. “Many interventional cardiologists are absolutely terrified of their patients having stent thrombosis, but with second-generation drug-eluting stents – the stents we’re putting in day in and day out – the risk of stent thrombosis is less than 1%. And in these two trials it was less than 0.5%. There’s more risk of having major bleeding events than there is of ischemia, so I think the balance is in favor of preventing bleeding. We know that major bleeding predicts short- and long-term mortality.”
COLCOT
This double-blind trial randomized 4,745 patients within 30 days post MI to low-dose colchicine or placebo on top of excellent rates of background guideline-directed medical therapy. The goal was to see if this anti-inflammatory agent could reduce cardiovascular events independent of any lipid-lowering effect, as was earlier seen with canakinumab in the CANTOS trial. It did so to a statistically significant but relatively modest degree, with a 5.5% rate of the composite cardiovascular events endpoint in the colchicine group and 7.1% in placebo-treated controls (N Engl J Med. 2019 Dec 26;381[26]:2497-505). But Dr. Bell was unimpressed.
“All-cause mortality was identical at 1.8% in both groups. So colchicine is not saving lives. In fact, the only real differences were in stroke – but the study wasn’t powered to look at stroke – and in urgent hospitalization for angina leading to revascularization, which is a soft endpoint,” he observed.
Plus, 2.5% of patients were lost to follow-up, which Dr. Bell considers “a little concerning” in a trial conducted in the current era.
“In my opinion, the evidence that colchicine is effective is weak, and I don’t think really supports the drug’s routine use post MI. We already send these patients out on numerous medications. We have to think about cost/benefit, and if a patient asks me: ‘Is this going to prevent another heart attack or make me live longer?’ I think the unequivocal answer is no,” he said.
These days colchicine is no longer an inexpensive drug, either, at an average cost of $300-$400 per month, the cardiologist added.
COMPLETE
This study randomized more than 4,000 patients with ST-segment elevation MI (STEMI) and multivessel disease to primary PCI of the culprit lesion only or to staged complete revascularization via PCI of all angiographically significant nonculprit lesions. Complete revascularization proved to be the superior strategy, with a 26% reduction in the risk of the composite of cardiovascular death or MI at a median of 3 years (N Engl J Med. 2019 Oct 10;381[15]:1411-21).
The optimal timing of the staged procedure remains unclear, since the study didn’t specify a protocol.
“I’m still a bit uncomfortable doing multivessel PCI at 2 o’clock in the morning in the setting of STEMI in someone I’ve never met before. I don’t think there’s a rush to do anything then. Often in this middle-of-the-night stuff, we miss things or we overinterpret things. I think it’s better to let the patient cool down, get to know them,” according to Dr. Bell.
EXCEL
Publication of the 5-year outcomes of the largest-ever randomized trial of PCI versus coronary artery bypass grafting (CABG) for left main coronary disease has led to furious controversy, with a few of the surgeons involved in the study opting to publically broadcast allegations of misbehavior on the part of the interventional cardiologist study leadership, charges that have been strongly denied.
The actual results are in line with findings reported from smaller randomized trials. At 5 years in EXCEL, there was no significant difference between the PCI and CABG groups in the primary composite endpoint of death, cerebrovascular accident, or MI (N Engl J Med. 2019 Nov 7;381[19]:1820-30). The all-cause mortality rate was 13% in the PCI arm and 9.9% with CABG, but this finding comes with a caveat.
“I’ll emphasize this trial was never powered to look at mortality. Neither were any of the other randomized trials. On the other hand, I don’t think you can necessarily ignore the finding of an absolute 3.1% difference,” Dr. Bell said.
PCI and CABG are both very good, mature therapies for left main disease, in his view. In the setting of more-complex coronary disease in younger patients, he often views the complete revascularization offered by surgery as the preferred option. On the other hand, in an 80-year-old with severe comorbidities, clearly PCI is attractive.
He considers the highly public nature of this interspecialty spat a regrettable black eye for the entire field of cardiovascular medicine. And he predicted that an ongoing outside neutral-party review of the study data and procedures will conclude, as he has, “there was no malfeasance at all in the trial.”
Dr. Bell reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – A repeated theme threading through much of one prominent interventional cardiologist’s personal list of the top five coronary artery disease (CAD) trials of the past year is that aspirin is very often more trouble than it’s worth.
“For some years I’ve been concerned that the only thing that aspirin does [in patients after percutaneous coronary intervention] is increase your risk of bleeding. It doesn’t really provide any additional ischemic protection,” Malcolm R. Bell, MBBS, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“I’ll remind you that, when we go back to the early stent days, observed Dr. Bell, professor of medicine and vice chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.
Here are the key takeaway messages from his five most important randomized trials in CAD during the last year.
AUGUSTUS
For years, cardiologists have grappled with how to best manage high-cardiovascular-risk patients with atrial fibrillation who seem like they might benefit from triple-antithrombotic therapy. AUGUSTUS supplied the answer: Don’t do it. Skip the aspirin and turn instead to a P2Y12 inhibitor plus a non–vitamin K antagonist oral anticoagulant (NOAC), rather than warfarin.
“I would like you to think of triple therapy as a triple threat. That’s really what triple therapy is all about”– a three-pronged threat to patient safety, Dr. Bell commented.
In AUGUSTUS, 4,614 patients with atrial fibrillation and CAD with an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) in 33 countries were placed on a P2Y12 inhibitor – most often clopidogrel – and randomized double blind to either apixaban (Eliquis) or warfarin, and further to aspirin or placebo, for 6 months of antithrombotic therapy. The strategy of a P2Y12 inhibitor and apixaban without aspirin was the clear winner, resulting in significantly less major bleeding, mortality, and hospitalizations than treatment with a P2Y12 inhibitor and warfarin, with or without aspirin. Most importantly, ischemic event rates didn’t differ between the apixaban and warfarin groups. And patients randomized to aspirin had rates of ischemic events and death or hospitalization similar to placebo-treated controls, meaning aspirin accomplished nothing (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
Dr. Bell noted that a meta-analysis of AUGUSTUS and three smaller randomized trials including more than 10,000 AUGUSTUS-type patients with atrial fibrillation concluded that a treatment strategy utilizing a NOAC and a P2Y12 inhibitor resulted in less bleeding than warfarin plus DAPT, and at no cost in terms of excess ischemic events. Moreover, regimens without aspirin resulted in less intracranial and other major bleeding without any difference in major adverse cardiovascular events (JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1880).
A key message of these four trials is that a NOAC is preferable to warfarin, so much so that, in high-risk patients who are already on warfarin, it’s worth considering a switch to a NOAC.
“And we should really be avoiding DAPT,” Dr. Bell added.
How soon after an ACS and/or PCI should patients with atrial fibrillation stop taking aspirin?
“In AUGUSTUS, randomization occurred at a median of 6 days, so we know that half the patients stopped their aspirin by then. In our own practice, we’re just dropping the aspirin for the most part before the patient leaves the hospital. I think if you leave them with instructions to stop the aspirin in a week’s time or a month’s time it just leads to confusion. And we should also remember that half of the major bleeding after PCI or ACS happens in the first 30 days, so it doesn’t make a lot of sense to say that we should continue it for a month and then drop it,” according to the cardiologist.
SMART-CHOICE and STOPDAPT-2
These two large multicenter studies demonstrate that DAPT can safely be stopped early if needed. SMART-CHOICE from South Korea and STOPDAPT-2 from Japan each randomized roughly 3,000 patients undergoing PCI to 12 months of DAPT or to DAPT for only 3 months or 1 month, respectively, at which point the aspirin was dropped and patients in the abbreviated DAPT arm continued on P2Y12 inhibitor monotherapy, mostly clopidogrel, for the remainder of the 12 months. In the Japanese STOPDAPT-2 trial, 1 month of DAPT proved superior to 12 months of DAPT for the primary composite endpoint of cardiovascular death, MI, stroke, definite stent thrombosis, or major or minor bleeding at 12 months (JAMA. 2019 Jun 25;321[24]:2414-27). In the South Korean SMART-CHOICE trial, 3 months of DAPT was noninferior to 12 months for major adverse cardiac and cerebrovascular events, and superior in terms of bleeding risk (JAMA. 2019 Jun 25;321[24]:2428-37). Of note, roughly half of patients in the two trials were lower-risk individuals undergoing PCI for stable angina.
Dr. Bell noted that, while the TWILIGHT trial (Ticagrelor With or Without Aspirin in High-Risk Patients After PCI) didn’t make his top-five list, it certainly fits well with the two East Asian studies. The TWILIGHT investigators randomized more than 7,000 patients to 12 months of DAPT or discontinuation of aspirin after 3 months. The result: a lower incidence of clinically relevant bleeding with ticagrelor monotherapy, and with no increased risk of death, MI, or stroke, compared with 12 months of DAPT (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
“Again, I would just question what the added value of aspirin is here,” Dr. Bell commented. “Many interventional cardiologists are absolutely terrified of their patients having stent thrombosis, but with second-generation drug-eluting stents – the stents we’re putting in day in and day out – the risk of stent thrombosis is less than 1%. And in these two trials it was less than 0.5%. There’s more risk of having major bleeding events than there is of ischemia, so I think the balance is in favor of preventing bleeding. We know that major bleeding predicts short- and long-term mortality.”
COLCOT
This double-blind trial randomized 4,745 patients within 30 days post MI to low-dose colchicine or placebo on top of excellent rates of background guideline-directed medical therapy. The goal was to see if this anti-inflammatory agent could reduce cardiovascular events independent of any lipid-lowering effect, as was earlier seen with canakinumab in the CANTOS trial. It did so to a statistically significant but relatively modest degree, with a 5.5% rate of the composite cardiovascular events endpoint in the colchicine group and 7.1% in placebo-treated controls (N Engl J Med. 2019 Dec 26;381[26]:2497-505). But Dr. Bell was unimpressed.
“All-cause mortality was identical at 1.8% in both groups. So colchicine is not saving lives. In fact, the only real differences were in stroke – but the study wasn’t powered to look at stroke – and in urgent hospitalization for angina leading to revascularization, which is a soft endpoint,” he observed.
Plus, 2.5% of patients were lost to follow-up, which Dr. Bell considers “a little concerning” in a trial conducted in the current era.
“In my opinion, the evidence that colchicine is effective is weak, and I don’t think really supports the drug’s routine use post MI. We already send these patients out on numerous medications. We have to think about cost/benefit, and if a patient asks me: ‘Is this going to prevent another heart attack or make me live longer?’ I think the unequivocal answer is no,” he said.
These days colchicine is no longer an inexpensive drug, either, at an average cost of $300-$400 per month, the cardiologist added.
COMPLETE
This study randomized more than 4,000 patients with ST-segment elevation MI (STEMI) and multivessel disease to primary PCI of the culprit lesion only or to staged complete revascularization via PCI of all angiographically significant nonculprit lesions. Complete revascularization proved to be the superior strategy, with a 26% reduction in the risk of the composite of cardiovascular death or MI at a median of 3 years (N Engl J Med. 2019 Oct 10;381[15]:1411-21).
The optimal timing of the staged procedure remains unclear, since the study didn’t specify a protocol.
“I’m still a bit uncomfortable doing multivessel PCI at 2 o’clock in the morning in the setting of STEMI in someone I’ve never met before. I don’t think there’s a rush to do anything then. Often in this middle-of-the-night stuff, we miss things or we overinterpret things. I think it’s better to let the patient cool down, get to know them,” according to Dr. Bell.
EXCEL
Publication of the 5-year outcomes of the largest-ever randomized trial of PCI versus coronary artery bypass grafting (CABG) for left main coronary disease has led to furious controversy, with a few of the surgeons involved in the study opting to publically broadcast allegations of misbehavior on the part of the interventional cardiologist study leadership, charges that have been strongly denied.
The actual results are in line with findings reported from smaller randomized trials. At 5 years in EXCEL, there was no significant difference between the PCI and CABG groups in the primary composite endpoint of death, cerebrovascular accident, or MI (N Engl J Med. 2019 Nov 7;381[19]:1820-30). The all-cause mortality rate was 13% in the PCI arm and 9.9% with CABG, but this finding comes with a caveat.
“I’ll emphasize this trial was never powered to look at mortality. Neither were any of the other randomized trials. On the other hand, I don’t think you can necessarily ignore the finding of an absolute 3.1% difference,” Dr. Bell said.
PCI and CABG are both very good, mature therapies for left main disease, in his view. In the setting of more-complex coronary disease in younger patients, he often views the complete revascularization offered by surgery as the preferred option. On the other hand, in an 80-year-old with severe comorbidities, clearly PCI is attractive.
He considers the highly public nature of this interspecialty spat a regrettable black eye for the entire field of cardiovascular medicine. And he predicted that an ongoing outside neutral-party review of the study data and procedures will conclude, as he has, “there was no malfeasance at all in the trial.”
Dr. Bell reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – A repeated theme threading through much of one prominent interventional cardiologist’s personal list of the top five coronary artery disease (CAD) trials of the past year is that aspirin is very often more trouble than it’s worth.
“For some years I’ve been concerned that the only thing that aspirin does [in patients after percutaneous coronary intervention] is increase your risk of bleeding. It doesn’t really provide any additional ischemic protection,” Malcolm R. Bell, MBBS, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“I’ll remind you that, when we go back to the early stent days, observed Dr. Bell, professor of medicine and vice chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.
Here are the key takeaway messages from his five most important randomized trials in CAD during the last year.
AUGUSTUS
For years, cardiologists have grappled with how to best manage high-cardiovascular-risk patients with atrial fibrillation who seem like they might benefit from triple-antithrombotic therapy. AUGUSTUS supplied the answer: Don’t do it. Skip the aspirin and turn instead to a P2Y12 inhibitor plus a non–vitamin K antagonist oral anticoagulant (NOAC), rather than warfarin.
“I would like you to think of triple therapy as a triple threat. That’s really what triple therapy is all about”– a three-pronged threat to patient safety, Dr. Bell commented.
In AUGUSTUS, 4,614 patients with atrial fibrillation and CAD with an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) in 33 countries were placed on a P2Y12 inhibitor – most often clopidogrel – and randomized double blind to either apixaban (Eliquis) or warfarin, and further to aspirin or placebo, for 6 months of antithrombotic therapy. The strategy of a P2Y12 inhibitor and apixaban without aspirin was the clear winner, resulting in significantly less major bleeding, mortality, and hospitalizations than treatment with a P2Y12 inhibitor and warfarin, with or without aspirin. Most importantly, ischemic event rates didn’t differ between the apixaban and warfarin groups. And patients randomized to aspirin had rates of ischemic events and death or hospitalization similar to placebo-treated controls, meaning aspirin accomplished nothing (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
Dr. Bell noted that a meta-analysis of AUGUSTUS and three smaller randomized trials including more than 10,000 AUGUSTUS-type patients with atrial fibrillation concluded that a treatment strategy utilizing a NOAC and a P2Y12 inhibitor resulted in less bleeding than warfarin plus DAPT, and at no cost in terms of excess ischemic events. Moreover, regimens without aspirin resulted in less intracranial and other major bleeding without any difference in major adverse cardiovascular events (JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1880).
A key message of these four trials is that a NOAC is preferable to warfarin, so much so that, in high-risk patients who are already on warfarin, it’s worth considering a switch to a NOAC.
“And we should really be avoiding DAPT,” Dr. Bell added.
How soon after an ACS and/or PCI should patients with atrial fibrillation stop taking aspirin?
“In AUGUSTUS, randomization occurred at a median of 6 days, so we know that half the patients stopped their aspirin by then. In our own practice, we’re just dropping the aspirin for the most part before the patient leaves the hospital. I think if you leave them with instructions to stop the aspirin in a week’s time or a month’s time it just leads to confusion. And we should also remember that half of the major bleeding after PCI or ACS happens in the first 30 days, so it doesn’t make a lot of sense to say that we should continue it for a month and then drop it,” according to the cardiologist.
SMART-CHOICE and STOPDAPT-2
These two large multicenter studies demonstrate that DAPT can safely be stopped early if needed. SMART-CHOICE from South Korea and STOPDAPT-2 from Japan each randomized roughly 3,000 patients undergoing PCI to 12 months of DAPT or to DAPT for only 3 months or 1 month, respectively, at which point the aspirin was dropped and patients in the abbreviated DAPT arm continued on P2Y12 inhibitor monotherapy, mostly clopidogrel, for the remainder of the 12 months. In the Japanese STOPDAPT-2 trial, 1 month of DAPT proved superior to 12 months of DAPT for the primary composite endpoint of cardiovascular death, MI, stroke, definite stent thrombosis, or major or minor bleeding at 12 months (JAMA. 2019 Jun 25;321[24]:2414-27). In the South Korean SMART-CHOICE trial, 3 months of DAPT was noninferior to 12 months for major adverse cardiac and cerebrovascular events, and superior in terms of bleeding risk (JAMA. 2019 Jun 25;321[24]:2428-37). Of note, roughly half of patients in the two trials were lower-risk individuals undergoing PCI for stable angina.
Dr. Bell noted that, while the TWILIGHT trial (Ticagrelor With or Without Aspirin in High-Risk Patients After PCI) didn’t make his top-five list, it certainly fits well with the two East Asian studies. The TWILIGHT investigators randomized more than 7,000 patients to 12 months of DAPT or discontinuation of aspirin after 3 months. The result: a lower incidence of clinically relevant bleeding with ticagrelor monotherapy, and with no increased risk of death, MI, or stroke, compared with 12 months of DAPT (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
“Again, I would just question what the added value of aspirin is here,” Dr. Bell commented. “Many interventional cardiologists are absolutely terrified of their patients having stent thrombosis, but with second-generation drug-eluting stents – the stents we’re putting in day in and day out – the risk of stent thrombosis is less than 1%. And in these two trials it was less than 0.5%. There’s more risk of having major bleeding events than there is of ischemia, so I think the balance is in favor of preventing bleeding. We know that major bleeding predicts short- and long-term mortality.”
COLCOT
This double-blind trial randomized 4,745 patients within 30 days post MI to low-dose colchicine or placebo on top of excellent rates of background guideline-directed medical therapy. The goal was to see if this anti-inflammatory agent could reduce cardiovascular events independent of any lipid-lowering effect, as was earlier seen with canakinumab in the CANTOS trial. It did so to a statistically significant but relatively modest degree, with a 5.5% rate of the composite cardiovascular events endpoint in the colchicine group and 7.1% in placebo-treated controls (N Engl J Med. 2019 Dec 26;381[26]:2497-505). But Dr. Bell was unimpressed.
“All-cause mortality was identical at 1.8% in both groups. So colchicine is not saving lives. In fact, the only real differences were in stroke – but the study wasn’t powered to look at stroke – and in urgent hospitalization for angina leading to revascularization, which is a soft endpoint,” he observed.
Plus, 2.5% of patients were lost to follow-up, which Dr. Bell considers “a little concerning” in a trial conducted in the current era.
“In my opinion, the evidence that colchicine is effective is weak, and I don’t think really supports the drug’s routine use post MI. We already send these patients out on numerous medications. We have to think about cost/benefit, and if a patient asks me: ‘Is this going to prevent another heart attack or make me live longer?’ I think the unequivocal answer is no,” he said.
These days colchicine is no longer an inexpensive drug, either, at an average cost of $300-$400 per month, the cardiologist added.
COMPLETE
This study randomized more than 4,000 patients with ST-segment elevation MI (STEMI) and multivessel disease to primary PCI of the culprit lesion only or to staged complete revascularization via PCI of all angiographically significant nonculprit lesions. Complete revascularization proved to be the superior strategy, with a 26% reduction in the risk of the composite of cardiovascular death or MI at a median of 3 years (N Engl J Med. 2019 Oct 10;381[15]:1411-21).
The optimal timing of the staged procedure remains unclear, since the study didn’t specify a protocol.
“I’m still a bit uncomfortable doing multivessel PCI at 2 o’clock in the morning in the setting of STEMI in someone I’ve never met before. I don’t think there’s a rush to do anything then. Often in this middle-of-the-night stuff, we miss things or we overinterpret things. I think it’s better to let the patient cool down, get to know them,” according to Dr. Bell.
EXCEL
Publication of the 5-year outcomes of the largest-ever randomized trial of PCI versus coronary artery bypass grafting (CABG) for left main coronary disease has led to furious controversy, with a few of the surgeons involved in the study opting to publically broadcast allegations of misbehavior on the part of the interventional cardiologist study leadership, charges that have been strongly denied.
The actual results are in line with findings reported from smaller randomized trials. At 5 years in EXCEL, there was no significant difference between the PCI and CABG groups in the primary composite endpoint of death, cerebrovascular accident, or MI (N Engl J Med. 2019 Nov 7;381[19]:1820-30). The all-cause mortality rate was 13% in the PCI arm and 9.9% with CABG, but this finding comes with a caveat.
“I’ll emphasize this trial was never powered to look at mortality. Neither were any of the other randomized trials. On the other hand, I don’t think you can necessarily ignore the finding of an absolute 3.1% difference,” Dr. Bell said.
PCI and CABG are both very good, mature therapies for left main disease, in his view. In the setting of more-complex coronary disease in younger patients, he often views the complete revascularization offered by surgery as the preferred option. On the other hand, in an 80-year-old with severe comorbidities, clearly PCI is attractive.
He considers the highly public nature of this interspecialty spat a regrettable black eye for the entire field of cardiovascular medicine. And he predicted that an ongoing outside neutral-party review of the study data and procedures will conclude, as he has, “there was no malfeasance at all in the trial.”
Dr. Bell reported having no financial conflicts regarding his presentation.
REPORTING FROM ACC SNOWMASS 2020
Novel percutaneous therapy for HOCM in development
SNOWMASS, COLO. – Percutaneous mitral valve plication shows early promise as a primary therapy for severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM), Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
He and his coworkers at the Minneapolis Heart Institute developed the novel procedure and published the first experience in the world with it. But further study in a much larger patient population is needed before percutaneous mitral plication is ready for prime time as a treatment for symptomatic HOCM, according to Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the institute.
Surgical myectomy is the guideline-recommended standard for treatment of patients with disabling symptoms caused by left ventricular outflow tract obstruction in the setting of hypertrophic cardiomyopathy. Alcohol septal ablation is a widely utilized alternative in patients who are frail and elderly or otherwise high-risk surgical candidates, or who lack ready access to an experienced surgical myectomy center, where the best outcomes are achieved. But roughly 20% of patients evaluated for alcohol septal ablation don’t have a septal artery anatomy amenable to the procedure. Other patients are put off by the 10%-50% risk that they will require a permanent pacemaker after alcohol septal ablation, depending upon their baseline ECG. And a small percentage of well-chosen patients – less than 10% – will experience inadequate gradient relief following alcohol septal ablation. So there is room for a novel therapeutic approach.
A percutaneous mitral clip–based solution, while technically challenging, offers several advantages over surgical myectomy and alcohol septal ablation. It’s less invasive, doesn’t create a potentially arrhythmogenic ablation scar requiring a permanent pacemaker, and it targets the mitral valve directly, addressing the mitral regurgitation that causes the left ventricular outflow tract obstruction. In contrast, both surgical myectomy and alcohol septal ablation target the ventricular septum.
Dr. Sorajja summarized his experience to date with percutaneous mitral valve plication for symptomatic HOCM, which encompasses the six patients in the published study (J Am Coll Cardiol. 2016 Jun 21;67[24]:2811-8) and the four others treated since then. The procedure was completed with placement of a single MitraClip in 9 of 10 patients. One patient experienced cardiac tamponade, resulting in a halt of the procedure; in the other nine, the intervention eliminated systolic anterior motion and markedly decreased the intraoperative left ventricular outflow tract gradient and mitral regurgitation.
At 2-5 years of follow-up, all patients have improved from New York Heart Association functional class III preprocedurally to class I or II. One patient required alcohol septal ablation. High systolic left ventricular outflow tract velocities in excess of 4 cm/s have been documented via follow-up echocardiography in some patients, the significance of which is under study.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Percutaneous mitral valve plication shows early promise as a primary therapy for severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM), Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
He and his coworkers at the Minneapolis Heart Institute developed the novel procedure and published the first experience in the world with it. But further study in a much larger patient population is needed before percutaneous mitral plication is ready for prime time as a treatment for symptomatic HOCM, according to Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the institute.
Surgical myectomy is the guideline-recommended standard for treatment of patients with disabling symptoms caused by left ventricular outflow tract obstruction in the setting of hypertrophic cardiomyopathy. Alcohol septal ablation is a widely utilized alternative in patients who are frail and elderly or otherwise high-risk surgical candidates, or who lack ready access to an experienced surgical myectomy center, where the best outcomes are achieved. But roughly 20% of patients evaluated for alcohol septal ablation don’t have a septal artery anatomy amenable to the procedure. Other patients are put off by the 10%-50% risk that they will require a permanent pacemaker after alcohol septal ablation, depending upon their baseline ECG. And a small percentage of well-chosen patients – less than 10% – will experience inadequate gradient relief following alcohol septal ablation. So there is room for a novel therapeutic approach.
A percutaneous mitral clip–based solution, while technically challenging, offers several advantages over surgical myectomy and alcohol septal ablation. It’s less invasive, doesn’t create a potentially arrhythmogenic ablation scar requiring a permanent pacemaker, and it targets the mitral valve directly, addressing the mitral regurgitation that causes the left ventricular outflow tract obstruction. In contrast, both surgical myectomy and alcohol septal ablation target the ventricular septum.
Dr. Sorajja summarized his experience to date with percutaneous mitral valve plication for symptomatic HOCM, which encompasses the six patients in the published study (J Am Coll Cardiol. 2016 Jun 21;67[24]:2811-8) and the four others treated since then. The procedure was completed with placement of a single MitraClip in 9 of 10 patients. One patient experienced cardiac tamponade, resulting in a halt of the procedure; in the other nine, the intervention eliminated systolic anterior motion and markedly decreased the intraoperative left ventricular outflow tract gradient and mitral regurgitation.
At 2-5 years of follow-up, all patients have improved from New York Heart Association functional class III preprocedurally to class I or II. One patient required alcohol septal ablation. High systolic left ventricular outflow tract velocities in excess of 4 cm/s have been documented via follow-up echocardiography in some patients, the significance of which is under study.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Percutaneous mitral valve plication shows early promise as a primary therapy for severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM), Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
He and his coworkers at the Minneapolis Heart Institute developed the novel procedure and published the first experience in the world with it. But further study in a much larger patient population is needed before percutaneous mitral plication is ready for prime time as a treatment for symptomatic HOCM, according to Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the institute.
Surgical myectomy is the guideline-recommended standard for treatment of patients with disabling symptoms caused by left ventricular outflow tract obstruction in the setting of hypertrophic cardiomyopathy. Alcohol septal ablation is a widely utilized alternative in patients who are frail and elderly or otherwise high-risk surgical candidates, or who lack ready access to an experienced surgical myectomy center, where the best outcomes are achieved. But roughly 20% of patients evaluated for alcohol septal ablation don’t have a septal artery anatomy amenable to the procedure. Other patients are put off by the 10%-50% risk that they will require a permanent pacemaker after alcohol septal ablation, depending upon their baseline ECG. And a small percentage of well-chosen patients – less than 10% – will experience inadequate gradient relief following alcohol septal ablation. So there is room for a novel therapeutic approach.
A percutaneous mitral clip–based solution, while technically challenging, offers several advantages over surgical myectomy and alcohol septal ablation. It’s less invasive, doesn’t create a potentially arrhythmogenic ablation scar requiring a permanent pacemaker, and it targets the mitral valve directly, addressing the mitral regurgitation that causes the left ventricular outflow tract obstruction. In contrast, both surgical myectomy and alcohol septal ablation target the ventricular septum.
Dr. Sorajja summarized his experience to date with percutaneous mitral valve plication for symptomatic HOCM, which encompasses the six patients in the published study (J Am Coll Cardiol. 2016 Jun 21;67[24]:2811-8) and the four others treated since then. The procedure was completed with placement of a single MitraClip in 9 of 10 patients. One patient experienced cardiac tamponade, resulting in a halt of the procedure; in the other nine, the intervention eliminated systolic anterior motion and markedly decreased the intraoperative left ventricular outflow tract gradient and mitral regurgitation.
At 2-5 years of follow-up, all patients have improved from New York Heart Association functional class III preprocedurally to class I or II. One patient required alcohol septal ablation. High systolic left ventricular outflow tract velocities in excess of 4 cm/s have been documented via follow-up echocardiography in some patients, the significance of which is under study.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
REPORTING FROM ACC SNOWMASS 2019
Look for alcohol septal ablation in the next HOCM guideline
SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.
Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.
The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.
The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).
In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”
The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).
The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.
The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.
One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).
However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.
“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.
At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.
Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.
The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.
The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).
In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”
The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).
The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.
The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.
One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).
However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.
“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.
At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.
Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.
The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.
The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).
In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”
The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).
The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.
The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.
One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).
However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.
“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.
At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Low-flow, low-gradient aortic stenosis with preserved LVEF: a special situation
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
REPORTING FROM ACC SNOWMASS 2019
Interventional cardiology pioneer reflects on field’s past, future
SNOWMASS, COLO. – When Spencer B. King III, MD, shared his thoughts about the future of interventional cardiology at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology, he felt compelled to offer a cautionary note about his past accuracy as a prognosticator.
It was way back at a poster session during the 1976 annual meeting of the American Heart Association in Miami Beach that he first met Andreas Gruentzig, MD, the father of percutaneous coronary intervention (PCI), who was presenting his initial revolutionary work on what he called “coronary transluminal angioplasty” in dogs.
“I looked at the poster and told him it would never work,” recalled Dr. King, professor emeritus of medicine at Emory University in Atlanta.
He soon changed his mind, however, because, to great acclaim, Dr. Gruentzig performed his successful first in-human coronary angioplasty the next year.
He noted that the Snowmass conference has played a significant role in the development of interventional cardiology in the United States. Dr. Gruentzig attended the conference in 1980, and Dr. King and others took that opportunity to persuade him to leave the bureaucratic confines of Zurich and join him at Emory later that year. The two cardiologists worked closely thereafter, refining angioplasty and conducting clinical trials until Dr. Gruentzig’s death in an airplane crash in Georgia in 1985 at age 46 years.
Turning to the future, Dr. King addressed a number of recent developments in interventional cardiology and rated their chances of significantly improving outcomes in patients with stable ischemic heart disease. He graded the innovations’ potential with use of a four-bar schema, akin to the WiFi signal power rating on a cell phone.
Noninvasive diagnostics to assess anatomy and physiology
“I think coronary CT angiography [CTA] will become the new diagnostic angiogram,” he predicted. “CTA has gotten much better. Outside the United States, in Europe and particularly in Japan and increasingly in China, CTA is becoming extremely common.”
Dr. King cited a recent multicenter study of blinded heart team treatment decision making on the basis of either CTA or conventional invasive angiography in 223 patients with left main or triple-vessel coronary artery disease (CAD). The level of agreement was impressively high: Coronary artery bypass grafting (CABG) was recommended for 28% of patients on the basis of CTA and 26% with conventional angiography, which suggests the feasibility of treatment decision making based solely on noninvasive imaging, history, and clinical examination (Eur Heart J. 2018 Nov 1;39[41]:3689-98).
“The other thing I like about the potential for noninvasive imaging to guide our interventions is that it may [replace] the diagnostic angiogram, which has largely become extinct,” the cardiologist continued. “If you think about it, patients are referred for an angiogram, and as far as informed consent is concerned, the patient is told to pack his bags, go off to some other city, get in the cath lab, and take the family because of what they might do to you. They might put stents in you, they might operate on you. We don’t have any idea because we don’t know what you have. And the patient has to buy into this. With CTA, the potential is there for people to actually know what you’re going to do to them before you do it.”
Coronary artery calcium scoring for primary risk assessment has taken on a prominent role in the latest practice guidelines. “I think it’s mostly helpful in getting people out of the system because they don’t have any calcium,” in Dr. King’s view.
PET and MRI will remain secondary noninvasive technologies. They will be used mostly to diagnose microvascular disease, but that’s information that doesn’t have much influence on whether interventional procedures are performed.
Overall, he gave noninvasive diagnostic tools high marks for their potential to improve outcomes in patients with stable ischemic heart disease.
“I give it a pretty robust three bars. Maybe you could give it four,” he said.
New pharmacologic therapies
Citing in particular the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and the sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. King declared, “It may be that the biggest, newest device in interventional cardiology going forward is not a device at all, it’s medical therapy.”
Interventional cardiologists either need to become expert in advanced medical therapies or else have access to someone in their group who prescribes those medications deftly.
“The future care of our patients will require more than percutaneous coronary intervention,” he emphasized.
So, four bars for the new medical therapies.
PCI and coronary artery bypass surgery
Both get one bar.
“PCI will be a partner of advanced antiatherosclerotic therapies, but will not be replaced by limiting antianginal therapy to medical treatment only,” Dr. King predicted.
Regarding CABG, he highlighted a recent systematic review and pooled analysis of 11,518 patients with stable ischemic heart disease randomized to CABG or PCI using drug-eluting or bare-metal stents in 11 clinical trials. CABG demonstrated a significant mortality benefit over PCI in patients with multivessel disease, particularly among those with diabetes or a higher degree of coronary disease complexity. However, there was no benefit in terms of 5-year all-cause mortality for CABG over PCI in those with left main disease (Lancet. 2018 Mar 10;391[10124]:9399-48).
“CABG will not go away. I predict that about 25% of revascularizations will continue to be done by surgery,” the cardiologist said. “For patients who can have complete revascularization by PCI, it’ll be done with advanced technology, but probably only by a subset of operators. We have a huge number of interventional cardiologists in this country, and some of them do a lot of these kinds of cases and some don’t.”
Endovascular imaging to optimize stent deployment and characterize plaque
Studies suggest that the use of intravascular ultrasound and other endovascular imaging technologies ends up providing better results than when they’re not employed.
“We see greatly increased use of IVUS [intravascular ultrasound], and not so much of optical coherence tomography, because of technical problems. So I give this at least two bars as far as moving practice forward,” according to Dr. King.
Bioresorbable scaffolds
This technology, which he noted “was supposed to solve all of our problems,” has tripped and fallen because of its associated increased risk of scaffold thrombosis. He cited a recent network meta-analysis of 91 randomized, controlled trials comparing bioresorbable scaffolds to current-generation metallic drug-eluting stents in more than 105,000 patients. The bioresorbable scaffolds had a significantly higher rate of scaffold thrombosis in the first 30 days after implantation, as well as from 31 days through 1 year and also beyond 1 year. In fact, there was a rising trend for scaffold thrombosis in the bioresorbable device group after the 1 year mark through a mean 3.7 years of follow-up (EuroIntervention. 2018 Mar 20;13[16]:1904-13).
“The overall impact of bioresorbable scaffolds has been nil. We don’t have them. Bioresorbable scaffolds may become noninferior to the best metal stents, but to become mainstream, they should show superiority,” the cardiologist said.
One bar, based on the uncertain possibility that new bioresorbable scaffolds now in early stages of development ultimately pan out.
Future training needs
PCI operator volumes are low, and that raises a host of issues regarding future training needs. Should fewer interventionalists be trained? Should training in endovascular imaging be a mandatory part of PCI training? Should interventional cardiology be divided into distinct coronary, structural heart, and peripheral vascular subspecialty domains involving different people, a change that is already informally underway in many places? How are operators who are interested in becoming experts in PCI for chronic total occlusion, diffuse disease, left main disease, or other complex cases going to get enough experience to be able to concentrate in those areas?
These are questions that will need to be addressed in the coming years. The answers will surely affect the delivery of interventional cardiology care.
Dr. King reported having no financial conflicts regarding his presentation.
SOURCE: King SB.
SNOWMASS, COLO. – When Spencer B. King III, MD, shared his thoughts about the future of interventional cardiology at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology, he felt compelled to offer a cautionary note about his past accuracy as a prognosticator.
It was way back at a poster session during the 1976 annual meeting of the American Heart Association in Miami Beach that he first met Andreas Gruentzig, MD, the father of percutaneous coronary intervention (PCI), who was presenting his initial revolutionary work on what he called “coronary transluminal angioplasty” in dogs.
“I looked at the poster and told him it would never work,” recalled Dr. King, professor emeritus of medicine at Emory University in Atlanta.
He soon changed his mind, however, because, to great acclaim, Dr. Gruentzig performed his successful first in-human coronary angioplasty the next year.
He noted that the Snowmass conference has played a significant role in the development of interventional cardiology in the United States. Dr. Gruentzig attended the conference in 1980, and Dr. King and others took that opportunity to persuade him to leave the bureaucratic confines of Zurich and join him at Emory later that year. The two cardiologists worked closely thereafter, refining angioplasty and conducting clinical trials until Dr. Gruentzig’s death in an airplane crash in Georgia in 1985 at age 46 years.
Turning to the future, Dr. King addressed a number of recent developments in interventional cardiology and rated their chances of significantly improving outcomes in patients with stable ischemic heart disease. He graded the innovations’ potential with use of a four-bar schema, akin to the WiFi signal power rating on a cell phone.
Noninvasive diagnostics to assess anatomy and physiology
“I think coronary CT angiography [CTA] will become the new diagnostic angiogram,” he predicted. “CTA has gotten much better. Outside the United States, in Europe and particularly in Japan and increasingly in China, CTA is becoming extremely common.”
Dr. King cited a recent multicenter study of blinded heart team treatment decision making on the basis of either CTA or conventional invasive angiography in 223 patients with left main or triple-vessel coronary artery disease (CAD). The level of agreement was impressively high: Coronary artery bypass grafting (CABG) was recommended for 28% of patients on the basis of CTA and 26% with conventional angiography, which suggests the feasibility of treatment decision making based solely on noninvasive imaging, history, and clinical examination (Eur Heart J. 2018 Nov 1;39[41]:3689-98).
“The other thing I like about the potential for noninvasive imaging to guide our interventions is that it may [replace] the diagnostic angiogram, which has largely become extinct,” the cardiologist continued. “If you think about it, patients are referred for an angiogram, and as far as informed consent is concerned, the patient is told to pack his bags, go off to some other city, get in the cath lab, and take the family because of what they might do to you. They might put stents in you, they might operate on you. We don’t have any idea because we don’t know what you have. And the patient has to buy into this. With CTA, the potential is there for people to actually know what you’re going to do to them before you do it.”
Coronary artery calcium scoring for primary risk assessment has taken on a prominent role in the latest practice guidelines. “I think it’s mostly helpful in getting people out of the system because they don’t have any calcium,” in Dr. King’s view.
PET and MRI will remain secondary noninvasive technologies. They will be used mostly to diagnose microvascular disease, but that’s information that doesn’t have much influence on whether interventional procedures are performed.
Overall, he gave noninvasive diagnostic tools high marks for their potential to improve outcomes in patients with stable ischemic heart disease.
“I give it a pretty robust three bars. Maybe you could give it four,” he said.
New pharmacologic therapies
Citing in particular the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and the sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. King declared, “It may be that the biggest, newest device in interventional cardiology going forward is not a device at all, it’s medical therapy.”
Interventional cardiologists either need to become expert in advanced medical therapies or else have access to someone in their group who prescribes those medications deftly.
“The future care of our patients will require more than percutaneous coronary intervention,” he emphasized.
So, four bars for the new medical therapies.
PCI and coronary artery bypass surgery
Both get one bar.
“PCI will be a partner of advanced antiatherosclerotic therapies, but will not be replaced by limiting antianginal therapy to medical treatment only,” Dr. King predicted.
Regarding CABG, he highlighted a recent systematic review and pooled analysis of 11,518 patients with stable ischemic heart disease randomized to CABG or PCI using drug-eluting or bare-metal stents in 11 clinical trials. CABG demonstrated a significant mortality benefit over PCI in patients with multivessel disease, particularly among those with diabetes or a higher degree of coronary disease complexity. However, there was no benefit in terms of 5-year all-cause mortality for CABG over PCI in those with left main disease (Lancet. 2018 Mar 10;391[10124]:9399-48).
“CABG will not go away. I predict that about 25% of revascularizations will continue to be done by surgery,” the cardiologist said. “For patients who can have complete revascularization by PCI, it’ll be done with advanced technology, but probably only by a subset of operators. We have a huge number of interventional cardiologists in this country, and some of them do a lot of these kinds of cases and some don’t.”
Endovascular imaging to optimize stent deployment and characterize plaque
Studies suggest that the use of intravascular ultrasound and other endovascular imaging technologies ends up providing better results than when they’re not employed.
“We see greatly increased use of IVUS [intravascular ultrasound], and not so much of optical coherence tomography, because of technical problems. So I give this at least two bars as far as moving practice forward,” according to Dr. King.
Bioresorbable scaffolds
This technology, which he noted “was supposed to solve all of our problems,” has tripped and fallen because of its associated increased risk of scaffold thrombosis. He cited a recent network meta-analysis of 91 randomized, controlled trials comparing bioresorbable scaffolds to current-generation metallic drug-eluting stents in more than 105,000 patients. The bioresorbable scaffolds had a significantly higher rate of scaffold thrombosis in the first 30 days after implantation, as well as from 31 days through 1 year and also beyond 1 year. In fact, there was a rising trend for scaffold thrombosis in the bioresorbable device group after the 1 year mark through a mean 3.7 years of follow-up (EuroIntervention. 2018 Mar 20;13[16]:1904-13).
“The overall impact of bioresorbable scaffolds has been nil. We don’t have them. Bioresorbable scaffolds may become noninferior to the best metal stents, but to become mainstream, they should show superiority,” the cardiologist said.
One bar, based on the uncertain possibility that new bioresorbable scaffolds now in early stages of development ultimately pan out.
Future training needs
PCI operator volumes are low, and that raises a host of issues regarding future training needs. Should fewer interventionalists be trained? Should training in endovascular imaging be a mandatory part of PCI training? Should interventional cardiology be divided into distinct coronary, structural heart, and peripheral vascular subspecialty domains involving different people, a change that is already informally underway in many places? How are operators who are interested in becoming experts in PCI for chronic total occlusion, diffuse disease, left main disease, or other complex cases going to get enough experience to be able to concentrate in those areas?
These are questions that will need to be addressed in the coming years. The answers will surely affect the delivery of interventional cardiology care.
Dr. King reported having no financial conflicts regarding his presentation.
SOURCE: King SB.
SNOWMASS, COLO. – When Spencer B. King III, MD, shared his thoughts about the future of interventional cardiology at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology, he felt compelled to offer a cautionary note about his past accuracy as a prognosticator.
It was way back at a poster session during the 1976 annual meeting of the American Heart Association in Miami Beach that he first met Andreas Gruentzig, MD, the father of percutaneous coronary intervention (PCI), who was presenting his initial revolutionary work on what he called “coronary transluminal angioplasty” in dogs.
“I looked at the poster and told him it would never work,” recalled Dr. King, professor emeritus of medicine at Emory University in Atlanta.
He soon changed his mind, however, because, to great acclaim, Dr. Gruentzig performed his successful first in-human coronary angioplasty the next year.
He noted that the Snowmass conference has played a significant role in the development of interventional cardiology in the United States. Dr. Gruentzig attended the conference in 1980, and Dr. King and others took that opportunity to persuade him to leave the bureaucratic confines of Zurich and join him at Emory later that year. The two cardiologists worked closely thereafter, refining angioplasty and conducting clinical trials until Dr. Gruentzig’s death in an airplane crash in Georgia in 1985 at age 46 years.
Turning to the future, Dr. King addressed a number of recent developments in interventional cardiology and rated their chances of significantly improving outcomes in patients with stable ischemic heart disease. He graded the innovations’ potential with use of a four-bar schema, akin to the WiFi signal power rating on a cell phone.
Noninvasive diagnostics to assess anatomy and physiology
“I think coronary CT angiography [CTA] will become the new diagnostic angiogram,” he predicted. “CTA has gotten much better. Outside the United States, in Europe and particularly in Japan and increasingly in China, CTA is becoming extremely common.”
Dr. King cited a recent multicenter study of blinded heart team treatment decision making on the basis of either CTA or conventional invasive angiography in 223 patients with left main or triple-vessel coronary artery disease (CAD). The level of agreement was impressively high: Coronary artery bypass grafting (CABG) was recommended for 28% of patients on the basis of CTA and 26% with conventional angiography, which suggests the feasibility of treatment decision making based solely on noninvasive imaging, history, and clinical examination (Eur Heart J. 2018 Nov 1;39[41]:3689-98).
“The other thing I like about the potential for noninvasive imaging to guide our interventions is that it may [replace] the diagnostic angiogram, which has largely become extinct,” the cardiologist continued. “If you think about it, patients are referred for an angiogram, and as far as informed consent is concerned, the patient is told to pack his bags, go off to some other city, get in the cath lab, and take the family because of what they might do to you. They might put stents in you, they might operate on you. We don’t have any idea because we don’t know what you have. And the patient has to buy into this. With CTA, the potential is there for people to actually know what you’re going to do to them before you do it.”
Coronary artery calcium scoring for primary risk assessment has taken on a prominent role in the latest practice guidelines. “I think it’s mostly helpful in getting people out of the system because they don’t have any calcium,” in Dr. King’s view.
PET and MRI will remain secondary noninvasive technologies. They will be used mostly to diagnose microvascular disease, but that’s information that doesn’t have much influence on whether interventional procedures are performed.
Overall, he gave noninvasive diagnostic tools high marks for their potential to improve outcomes in patients with stable ischemic heart disease.
“I give it a pretty robust three bars. Maybe you could give it four,” he said.
New pharmacologic therapies
Citing in particular the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and the sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. King declared, “It may be that the biggest, newest device in interventional cardiology going forward is not a device at all, it’s medical therapy.”
Interventional cardiologists either need to become expert in advanced medical therapies or else have access to someone in their group who prescribes those medications deftly.
“The future care of our patients will require more than percutaneous coronary intervention,” he emphasized.
So, four bars for the new medical therapies.
PCI and coronary artery bypass surgery
Both get one bar.
“PCI will be a partner of advanced antiatherosclerotic therapies, but will not be replaced by limiting antianginal therapy to medical treatment only,” Dr. King predicted.
Regarding CABG, he highlighted a recent systematic review and pooled analysis of 11,518 patients with stable ischemic heart disease randomized to CABG or PCI using drug-eluting or bare-metal stents in 11 clinical trials. CABG demonstrated a significant mortality benefit over PCI in patients with multivessel disease, particularly among those with diabetes or a higher degree of coronary disease complexity. However, there was no benefit in terms of 5-year all-cause mortality for CABG over PCI in those with left main disease (Lancet. 2018 Mar 10;391[10124]:9399-48).
“CABG will not go away. I predict that about 25% of revascularizations will continue to be done by surgery,” the cardiologist said. “For patients who can have complete revascularization by PCI, it’ll be done with advanced technology, but probably only by a subset of operators. We have a huge number of interventional cardiologists in this country, and some of them do a lot of these kinds of cases and some don’t.”
Endovascular imaging to optimize stent deployment and characterize plaque
Studies suggest that the use of intravascular ultrasound and other endovascular imaging technologies ends up providing better results than when they’re not employed.
“We see greatly increased use of IVUS [intravascular ultrasound], and not so much of optical coherence tomography, because of technical problems. So I give this at least two bars as far as moving practice forward,” according to Dr. King.
Bioresorbable scaffolds
This technology, which he noted “was supposed to solve all of our problems,” has tripped and fallen because of its associated increased risk of scaffold thrombosis. He cited a recent network meta-analysis of 91 randomized, controlled trials comparing bioresorbable scaffolds to current-generation metallic drug-eluting stents in more than 105,000 patients. The bioresorbable scaffolds had a significantly higher rate of scaffold thrombosis in the first 30 days after implantation, as well as from 31 days through 1 year and also beyond 1 year. In fact, there was a rising trend for scaffold thrombosis in the bioresorbable device group after the 1 year mark through a mean 3.7 years of follow-up (EuroIntervention. 2018 Mar 20;13[16]:1904-13).
“The overall impact of bioresorbable scaffolds has been nil. We don’t have them. Bioresorbable scaffolds may become noninferior to the best metal stents, but to become mainstream, they should show superiority,” the cardiologist said.
One bar, based on the uncertain possibility that new bioresorbable scaffolds now in early stages of development ultimately pan out.
Future training needs
PCI operator volumes are low, and that raises a host of issues regarding future training needs. Should fewer interventionalists be trained? Should training in endovascular imaging be a mandatory part of PCI training? Should interventional cardiology be divided into distinct coronary, structural heart, and peripheral vascular subspecialty domains involving different people, a change that is already informally underway in many places? How are operators who are interested in becoming experts in PCI for chronic total occlusion, diffuse disease, left main disease, or other complex cases going to get enough experience to be able to concentrate in those areas?
These are questions that will need to be addressed in the coming years. The answers will surely affect the delivery of interventional cardiology care.
Dr. King reported having no financial conflicts regarding his presentation.
SOURCE: King SB.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Eisenmenger syndrome is a minefield for unwary physicians
SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.
“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.
She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?
“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.
Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?
No and no, Dr. Warnes emphasized.
“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.
Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.
“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.
Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.
“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.
Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.
So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.
Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.
Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.
“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.
Dr. Warnes reported having no financial conflicts regarding her presentation.
SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.
“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.
She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?
“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.
Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?
No and no, Dr. Warnes emphasized.
“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.
Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.
“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.
Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.
“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.
Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.
So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.
Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.
Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.
“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.
Dr. Warnes reported having no financial conflicts regarding her presentation.
SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.
“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.
She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?
“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.
Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?
No and no, Dr. Warnes emphasized.
“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.
Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.
“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.
Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.
“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.
Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.
So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.
Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.
Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.
“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.
Dr. Warnes reported having no financial conflicts regarding her presentation.
REPORTING FROM ACC SNOWMASS 2019
Five pitfalls in optimizing medical management of HFrEF
SNOWMASS, COLO. – Many of the abundant missed opportunities to optimize pharmacotherapy for heart failure with reduced ejection fraction revolve around not getting fully on board with the guideline-directed medical therapy shown to be highly effective at improving clinical outcomes, Akshay S. Desai, MD, asserted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“If you take nothing else away from this talk, is really quite profound,” declared Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, and a cardiologist at Harvard Medical School, Boston.
He highlighted five common traps or pitfalls for physicians with regard to medical therapy of patients with heart failure with reduced ejection fraction (HFrEF):
Underutilization of guideline-directed medical therapy
The current ACC/American Heart Association/Heart Failure Society of America guidelines on heart failure management (Circulation. 2017 Aug 8;136[6]:e137-61) reflect 20 years of impressive progress in improving heart failure outcomes through the use of increasingly effective guideline-directed medical therapy (GDMT). The magnitude of this improvement was nicely captured in a meta-analysis of 57 randomized controlled trials published during 1987-2015. The meta-analysis showed that, although ACE inhibitor therapy alone had no significant impact on all-cause mortality compared to placebo in patients with HFrEF, the sequential addition of guideline-directed drugs conferred stepwise improvements in survival. This approach culminated in a 56% reduction in all-cause mortality with the combination of an ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA), compared with placebo, and a 63% reduction with an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and MRA (Circ Heart Fail. 2017 Jan;10(1). pii: e003529).
Moreover, the benefits of contemporary GDMT extend beyond reductions in all-cause mortality, death due to heart failure, and heart failure–related hospitalizations into areas where one wouldn’t necessarily have expected to see much benefit. For example, an analysis of data on more than 40,000 HFrEF patients in 12 clinical trials showed a sharp decline in the rate of sudden death over the years as new agents were incorporated into GDMT. The cumulative incidence of sudden death within 90 days after randomization plunged from 2.4% in the earliest trial to 1.0% in the most recent one (N Engl J Med. 2017 Jul 6;377[1]:41-51).
“We’re at the point where we now question whether routine use of implantable cardioverter-defibrillators in primary prevention patients with nonischemic heart failure is really worthwhile on the backdrop of effective medical therapy,” Dr. Desai observed.
But there’s a problem: “We don’t do a great job with GDMT, even with this incredible evidence base that we have,” the cardiologist said.
He cited a report from the CHAMP-HF registry that scrutinized the use of GDMT in more than 3,500 ambulatory HFrEF patients in 150 U.S. primary care and cardiology practices. It found that 67% of patients deemed eligible for an MRA weren’t on one. Neither were 33% with no contraindications to beta-blocker therapy and 27% who were eligible for an ACE inhibitor, angiotensin receptor blocker (ARB), or ARNI (J Am Coll Cardiol. 2018 Jul 24;72[4]:351-66).
“This highlights a huge opportunity for further guideline-directed optimization of therapy,” he said.
Underdosing of GDMT
The CHAMP-HF registry contained further disappointing news regarding the state of treatment of patients with HFrEF in ambulatory settings: Among those patients who were on GDMT, very few were receiving the recommended target doses of the medications as established in major clinical trials and specified in the guidelines. Only 14% of patients on an ARNI were on the target dose, as were 28% on a beta-blocker, and 17% of those on an ACE inhibitor or ARB. And among patients who were eligible for all classes of GDMT, just 1% were simultaneously on the target doses of an MRA, beta-blocker, and ARNI, ACE inhibitor, or ARB. This despite solid evidence that, although some benefit is derived from initiating these medications, incremental benefit comes from dose titration.
“Even for those of us who feel like we do this quite well, if we examine our practices systematically – and we’ve done this in our own practices at Brigham and Women’s – you see that a lot of eligible patients aren’t on optimal therapy. And you might argue that many of them have contraindications, but even when you do a deep dive into the literature or the electronic medical record and ask the question – Why is this patient with normal renal function and normal potassium with class II HFrEF not on an MRA? – sometimes it’s hard to establish why that’s the case,” said Dr. Desai.
Interrupting GDMT during hospitalizations
This is common practice. But in fact, continuation of GDMT is generally well tolerated in the setting of acute decompensated heart failure in the absence of severe hypotension and cardiogenic shock. Moreover, in-hospital discontinuation or dose reduction is associated with increased risks of readmission and mortality.
And in treatment-naive HFrEF patients, what better place to introduce a medication and assess its tolerability than the hospital? Plus, medications prescribed at discharge are more likely to be continued in the outpatient setting, he noted.
Being seduced by the illusion of stability
The guidelines state that patients with NYHA class II or III HFrEF who tolerate an ACE inhibitor or ARB should be transitioned to an ARNI to further reduce their risk of morbidity and mortality. Yet many physicians wait to make the switch until clinical decompensation occurs. That’s a mistake, as was demonstrated in the landmark PARADIGM-HF trial. Twenty percent of study participants without a prior hospitalization for heart failure experienced cardiovascular death or heart failure hospitalization during the follow-up period. Patients who were clinically stable as defined by no prior heart failure hospitalization or none within 3 months prior to enrollment were as likely to benefit from ARNI therapy with sacubitril/valsartan (Entresto) as were those with a recent decompensation (JACC Heart Fail. 2016 Oct;4[10]:816-22). “A key message is that stability is an illusion in patients with symptomatic heart failure,”said Dr. Desai. “In PARADIGM-HF, the first event for about half of patients was not heralded by a worsening of symptoms or a heart failure hospitalization, it was an abrupt death at home. This may mean that a missed opportunity to optimize treatment may not come back to you down the road, so waiting until patients get worse in order to optimize their therapy may not be the best strategy.”
Inadequate laboratory monitoring
The MRAs, spironolactone and eplerenone (Inspra), are the GDMT drugs for which laboratory surveillance takes on the greatest importance because of their potential to induce hyperkalemia. The guidelines are clear that a potassium level and measurement of renal function should be obtained within a week of initiating therapy with an MRA, again at 4 weeks, and periodically thereafter.
“In general, this is done in clinical practice almost never,” Dr. Desai stressed.
These agents should be avoided in patients with prior hyperkalemia or advanced chronic kidney disease, and used with care in groups known to be at increased risk for hyperkalemia, including the elderly and patients with diabetes.
He considers spironolactone equivalent to eplerenone so long as the dosing is adequate. He generally reserves eplerenone for patients with poorly tolerated antiandrogenic effects on spironolactone.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
SNOWMASS, COLO. – Many of the abundant missed opportunities to optimize pharmacotherapy for heart failure with reduced ejection fraction revolve around not getting fully on board with the guideline-directed medical therapy shown to be highly effective at improving clinical outcomes, Akshay S. Desai, MD, asserted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“If you take nothing else away from this talk, is really quite profound,” declared Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, and a cardiologist at Harvard Medical School, Boston.
He highlighted five common traps or pitfalls for physicians with regard to medical therapy of patients with heart failure with reduced ejection fraction (HFrEF):
Underutilization of guideline-directed medical therapy
The current ACC/American Heart Association/Heart Failure Society of America guidelines on heart failure management (Circulation. 2017 Aug 8;136[6]:e137-61) reflect 20 years of impressive progress in improving heart failure outcomes through the use of increasingly effective guideline-directed medical therapy (GDMT). The magnitude of this improvement was nicely captured in a meta-analysis of 57 randomized controlled trials published during 1987-2015. The meta-analysis showed that, although ACE inhibitor therapy alone had no significant impact on all-cause mortality compared to placebo in patients with HFrEF, the sequential addition of guideline-directed drugs conferred stepwise improvements in survival. This approach culminated in a 56% reduction in all-cause mortality with the combination of an ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA), compared with placebo, and a 63% reduction with an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and MRA (Circ Heart Fail. 2017 Jan;10(1). pii: e003529).
Moreover, the benefits of contemporary GDMT extend beyond reductions in all-cause mortality, death due to heart failure, and heart failure–related hospitalizations into areas where one wouldn’t necessarily have expected to see much benefit. For example, an analysis of data on more than 40,000 HFrEF patients in 12 clinical trials showed a sharp decline in the rate of sudden death over the years as new agents were incorporated into GDMT. The cumulative incidence of sudden death within 90 days after randomization plunged from 2.4% in the earliest trial to 1.0% in the most recent one (N Engl J Med. 2017 Jul 6;377[1]:41-51).
“We’re at the point where we now question whether routine use of implantable cardioverter-defibrillators in primary prevention patients with nonischemic heart failure is really worthwhile on the backdrop of effective medical therapy,” Dr. Desai observed.
But there’s a problem: “We don’t do a great job with GDMT, even with this incredible evidence base that we have,” the cardiologist said.
He cited a report from the CHAMP-HF registry that scrutinized the use of GDMT in more than 3,500 ambulatory HFrEF patients in 150 U.S. primary care and cardiology practices. It found that 67% of patients deemed eligible for an MRA weren’t on one. Neither were 33% with no contraindications to beta-blocker therapy and 27% who were eligible for an ACE inhibitor, angiotensin receptor blocker (ARB), or ARNI (J Am Coll Cardiol. 2018 Jul 24;72[4]:351-66).
“This highlights a huge opportunity for further guideline-directed optimization of therapy,” he said.
Underdosing of GDMT
The CHAMP-HF registry contained further disappointing news regarding the state of treatment of patients with HFrEF in ambulatory settings: Among those patients who were on GDMT, very few were receiving the recommended target doses of the medications as established in major clinical trials and specified in the guidelines. Only 14% of patients on an ARNI were on the target dose, as were 28% on a beta-blocker, and 17% of those on an ACE inhibitor or ARB. And among patients who were eligible for all classes of GDMT, just 1% were simultaneously on the target doses of an MRA, beta-blocker, and ARNI, ACE inhibitor, or ARB. This despite solid evidence that, although some benefit is derived from initiating these medications, incremental benefit comes from dose titration.
“Even for those of us who feel like we do this quite well, if we examine our practices systematically – and we’ve done this in our own practices at Brigham and Women’s – you see that a lot of eligible patients aren’t on optimal therapy. And you might argue that many of them have contraindications, but even when you do a deep dive into the literature or the electronic medical record and ask the question – Why is this patient with normal renal function and normal potassium with class II HFrEF not on an MRA? – sometimes it’s hard to establish why that’s the case,” said Dr. Desai.
Interrupting GDMT during hospitalizations
This is common practice. But in fact, continuation of GDMT is generally well tolerated in the setting of acute decompensated heart failure in the absence of severe hypotension and cardiogenic shock. Moreover, in-hospital discontinuation or dose reduction is associated with increased risks of readmission and mortality.
And in treatment-naive HFrEF patients, what better place to introduce a medication and assess its tolerability than the hospital? Plus, medications prescribed at discharge are more likely to be continued in the outpatient setting, he noted.
Being seduced by the illusion of stability
The guidelines state that patients with NYHA class II or III HFrEF who tolerate an ACE inhibitor or ARB should be transitioned to an ARNI to further reduce their risk of morbidity and mortality. Yet many physicians wait to make the switch until clinical decompensation occurs. That’s a mistake, as was demonstrated in the landmark PARADIGM-HF trial. Twenty percent of study participants without a prior hospitalization for heart failure experienced cardiovascular death or heart failure hospitalization during the follow-up period. Patients who were clinically stable as defined by no prior heart failure hospitalization or none within 3 months prior to enrollment were as likely to benefit from ARNI therapy with sacubitril/valsartan (Entresto) as were those with a recent decompensation (JACC Heart Fail. 2016 Oct;4[10]:816-22). “A key message is that stability is an illusion in patients with symptomatic heart failure,”said Dr. Desai. “In PARADIGM-HF, the first event for about half of patients was not heralded by a worsening of symptoms or a heart failure hospitalization, it was an abrupt death at home. This may mean that a missed opportunity to optimize treatment may not come back to you down the road, so waiting until patients get worse in order to optimize their therapy may not be the best strategy.”
Inadequate laboratory monitoring
The MRAs, spironolactone and eplerenone (Inspra), are the GDMT drugs for which laboratory surveillance takes on the greatest importance because of their potential to induce hyperkalemia. The guidelines are clear that a potassium level and measurement of renal function should be obtained within a week of initiating therapy with an MRA, again at 4 weeks, and periodically thereafter.
“In general, this is done in clinical practice almost never,” Dr. Desai stressed.
These agents should be avoided in patients with prior hyperkalemia or advanced chronic kidney disease, and used with care in groups known to be at increased risk for hyperkalemia, including the elderly and patients with diabetes.
He considers spironolactone equivalent to eplerenone so long as the dosing is adequate. He generally reserves eplerenone for patients with poorly tolerated antiandrogenic effects on spironolactone.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
SNOWMASS, COLO. – Many of the abundant missed opportunities to optimize pharmacotherapy for heart failure with reduced ejection fraction revolve around not getting fully on board with the guideline-directed medical therapy shown to be highly effective at improving clinical outcomes, Akshay S. Desai, MD, asserted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“If you take nothing else away from this talk, is really quite profound,” declared Dr. Desai, director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, and a cardiologist at Harvard Medical School, Boston.
He highlighted five common traps or pitfalls for physicians with regard to medical therapy of patients with heart failure with reduced ejection fraction (HFrEF):
Underutilization of guideline-directed medical therapy
The current ACC/American Heart Association/Heart Failure Society of America guidelines on heart failure management (Circulation. 2017 Aug 8;136[6]:e137-61) reflect 20 years of impressive progress in improving heart failure outcomes through the use of increasingly effective guideline-directed medical therapy (GDMT). The magnitude of this improvement was nicely captured in a meta-analysis of 57 randomized controlled trials published during 1987-2015. The meta-analysis showed that, although ACE inhibitor therapy alone had no significant impact on all-cause mortality compared to placebo in patients with HFrEF, the sequential addition of guideline-directed drugs conferred stepwise improvements in survival. This approach culminated in a 56% reduction in all-cause mortality with the combination of an ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA), compared with placebo, and a 63% reduction with an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and MRA (Circ Heart Fail. 2017 Jan;10(1). pii: e003529).
Moreover, the benefits of contemporary GDMT extend beyond reductions in all-cause mortality, death due to heart failure, and heart failure–related hospitalizations into areas where one wouldn’t necessarily have expected to see much benefit. For example, an analysis of data on more than 40,000 HFrEF patients in 12 clinical trials showed a sharp decline in the rate of sudden death over the years as new agents were incorporated into GDMT. The cumulative incidence of sudden death within 90 days after randomization plunged from 2.4% in the earliest trial to 1.0% in the most recent one (N Engl J Med. 2017 Jul 6;377[1]:41-51).
“We’re at the point where we now question whether routine use of implantable cardioverter-defibrillators in primary prevention patients with nonischemic heart failure is really worthwhile on the backdrop of effective medical therapy,” Dr. Desai observed.
But there’s a problem: “We don’t do a great job with GDMT, even with this incredible evidence base that we have,” the cardiologist said.
He cited a report from the CHAMP-HF registry that scrutinized the use of GDMT in more than 3,500 ambulatory HFrEF patients in 150 U.S. primary care and cardiology practices. It found that 67% of patients deemed eligible for an MRA weren’t on one. Neither were 33% with no contraindications to beta-blocker therapy and 27% who were eligible for an ACE inhibitor, angiotensin receptor blocker (ARB), or ARNI (J Am Coll Cardiol. 2018 Jul 24;72[4]:351-66).
“This highlights a huge opportunity for further guideline-directed optimization of therapy,” he said.
Underdosing of GDMT
The CHAMP-HF registry contained further disappointing news regarding the state of treatment of patients with HFrEF in ambulatory settings: Among those patients who were on GDMT, very few were receiving the recommended target doses of the medications as established in major clinical trials and specified in the guidelines. Only 14% of patients on an ARNI were on the target dose, as were 28% on a beta-blocker, and 17% of those on an ACE inhibitor or ARB. And among patients who were eligible for all classes of GDMT, just 1% were simultaneously on the target doses of an MRA, beta-blocker, and ARNI, ACE inhibitor, or ARB. This despite solid evidence that, although some benefit is derived from initiating these medications, incremental benefit comes from dose titration.
“Even for those of us who feel like we do this quite well, if we examine our practices systematically – and we’ve done this in our own practices at Brigham and Women’s – you see that a lot of eligible patients aren’t on optimal therapy. And you might argue that many of them have contraindications, but even when you do a deep dive into the literature or the electronic medical record and ask the question – Why is this patient with normal renal function and normal potassium with class II HFrEF not on an MRA? – sometimes it’s hard to establish why that’s the case,” said Dr. Desai.
Interrupting GDMT during hospitalizations
This is common practice. But in fact, continuation of GDMT is generally well tolerated in the setting of acute decompensated heart failure in the absence of severe hypotension and cardiogenic shock. Moreover, in-hospital discontinuation or dose reduction is associated with increased risks of readmission and mortality.
And in treatment-naive HFrEF patients, what better place to introduce a medication and assess its tolerability than the hospital? Plus, medications prescribed at discharge are more likely to be continued in the outpatient setting, he noted.
Being seduced by the illusion of stability
The guidelines state that patients with NYHA class II or III HFrEF who tolerate an ACE inhibitor or ARB should be transitioned to an ARNI to further reduce their risk of morbidity and mortality. Yet many physicians wait to make the switch until clinical decompensation occurs. That’s a mistake, as was demonstrated in the landmark PARADIGM-HF trial. Twenty percent of study participants without a prior hospitalization for heart failure experienced cardiovascular death or heart failure hospitalization during the follow-up period. Patients who were clinically stable as defined by no prior heart failure hospitalization or none within 3 months prior to enrollment were as likely to benefit from ARNI therapy with sacubitril/valsartan (Entresto) as were those with a recent decompensation (JACC Heart Fail. 2016 Oct;4[10]:816-22). “A key message is that stability is an illusion in patients with symptomatic heart failure,”said Dr. Desai. “In PARADIGM-HF, the first event for about half of patients was not heralded by a worsening of symptoms or a heart failure hospitalization, it was an abrupt death at home. This may mean that a missed opportunity to optimize treatment may not come back to you down the road, so waiting until patients get worse in order to optimize their therapy may not be the best strategy.”
Inadequate laboratory monitoring
The MRAs, spironolactone and eplerenone (Inspra), are the GDMT drugs for which laboratory surveillance takes on the greatest importance because of their potential to induce hyperkalemia. The guidelines are clear that a potassium level and measurement of renal function should be obtained within a week of initiating therapy with an MRA, again at 4 weeks, and periodically thereafter.
“In general, this is done in clinical practice almost never,” Dr. Desai stressed.
These agents should be avoided in patients with prior hyperkalemia or advanced chronic kidney disease, and used with care in groups known to be at increased risk for hyperkalemia, including the elderly and patients with diabetes.
He considers spironolactone equivalent to eplerenone so long as the dosing is adequate. He generally reserves eplerenone for patients with poorly tolerated antiandrogenic effects on spironolactone.
Dr. Desai reported serving as a paid consultant to more than half a dozen pharmaceutical or medical device companies.
REPORTING FROM ACC SNOWMASS 2019
Infective endocarditis isn’t what it used to be
SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.
“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.
“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.
This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
Outcomes are ‘sobering’
In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.
Refer early for multimodality imaging and surgical consultation
Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.
The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).
Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.
If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.
“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.
The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
Don’t use half measures when it comes to removal of cardiac implanted electronic devices
The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.
“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
Know when the cardiologist should say ‘no’ to early aggressive surgery
While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.
“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.
“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.
This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
Outcomes are ‘sobering’
In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.
Refer early for multimodality imaging and surgical consultation
Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.
The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).
Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.
If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.
“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.
The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
Don’t use half measures when it comes to removal of cardiac implanted electronic devices
The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.
“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
Know when the cardiologist should say ‘no’ to early aggressive surgery
While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.
“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.
“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.
This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
Outcomes are ‘sobering’
In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.
Refer early for multimodality imaging and surgical consultation
Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.
The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).
Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.
If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.
“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.
The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
Don’t use half measures when it comes to removal of cardiac implanted electronic devices
The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.
“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
Know when the cardiologist should say ‘no’ to early aggressive surgery
While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).
Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.
REPORTING FROM ACC SNOWMASS 2019
Not all AF maze operations are aMAZE-ing
SNOWMASS, COLO. – The term “maze procedure” for surgical ablation of atrial fibrillation is bandied about rather loosely these days, but as far as Hartzell V. Schaff, MD, is concerned, the operation of choice remains the classic cut-and-sew maze III procedure developed by James L. Cox, MD, while at Washington University, St. Louis.
“The classic Cox maze III, the cut-and-sew maze, is the best procedure for getting rid of atrial fibrillation and is in my view the gold standard. Some people argue that transmurality isn’t important, but it can occur because of gap lesions,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Unlike modifications of the Cox maze III – such as the mini maze or the maze IV, which utilizes radiofrequency energy or cryoablation to create scars in an effort to achieve pulmonary vein isolation – the maze III cannot be done as a minimally invasive procedure. After all, it requires making incisions in both atria, along with aortic cross-clamping and cardiopulmonary bypass. But it has a significantly higher long-term rate of freedom from recurrent atrial fibrillation (AF) than the other operations. And crucially, it enables the surgeon to readily obliterate the left atrial appendage.
“The most important thing when you do any surgical procedure for atrial fibrillation, I think, is getting rid of the left atrial appendage. When you do cut-and-sew maze, that’s done 100% of the time,” explained Dr. Schaff, professor of surgery at the Mayo Clinic in Rochester, Minn.
“We really have a lot of work left to do as surgeons in improving the outcome of surgery for atrial fibrillation. One of the things we as surgeons don’t do well is getting rid of the left atrial appendage. This ought to be done in every patient that has surgical ablation for atrial fibrillation,” according to the cardiothoracic surgeon.
And yet, he continued, in a series of nearly 87,000 patients with AF who underwent nonemergent cardiac surgery in the Society of Thoracic Surgeons database, 48.0% of whom underwent surgical ablation for AF, only 63.9% of those who had standalone ablation for lone AF got their left atrial appendage dealt with, compared with 86%-89% of those who underwent concomitant cardiac surgery, such as mitral valve repair or replacement (Ann Thorac Surg. 2017 Aug;104[2]:493-500).
“That’s awful, really. And the reason for that low left atrial appendage obliteration rate is this: For many of those patients who had surgery for lone atrial fibrillation, the surgeons were trying to do minimally invasive surgery, where they do pulmonary vein isolation on the right side, so they don’t have access to the left atrial appendage,” Dr. Schaff said.
“In the past,” he recalled, “we would ligate the left atrial appendage. Nowadays because of echocardiographic studies that show there’s persistent patency in a sizable percentage of patients, we amputate the left atrial appendage in almost all of the patients.”
The terminology surrounding surgical ablation for AF, in his view, has become rather confusing. “Most of you, when you refer a patient for surgical ablation for AF, the surgeons will just say they do a maze procedure,” Dr. Schaff cautioned. “Somehow, all of that [maze IV, mini maze] today is lumped together as a classic maze procedure, but it’s really not. We have different lesion sets and energy sources.”
And different outcomes as well. In a series of 1,189 adults who underwent surgical ablation for AF at the Mayo Clinic, of whom 44% had a biatrial cut-and-sew maze while the rest had surgical cryotherapy, radiofrequency ablation, or a combination of the two, the rate of freedom from AF 1 year post surgery was 85% with the cut-and-sew maze versus 71% with the alternatives. At 5 years or more, the rates were 78% and 52%, respectively. In a multivariate analysis, freedom from AF was independently associated with preoperative paroxysmal rather than permanent AF, performance of the classic maze III procedure, concomitant treatment of associated mitral valve disease, and younger age.
Moreover, rates of the major early postoperative complications – stroke, bleeding, and renal failure – were similar in the cut-and-sew maze III and other groups.
“So a lesser procedure doesn’t necessarily mean fewer complications,” Dr. Schaff noted.
One of the criticisms levied against the maze III is that it’s too much surgery for AF. But it’s actually relatively inexpensive because the disposables – suture, needles, scalpel – are those used in the commonly performed concomitant cardiac surgical procedures. “The Cox maze III does take extra time, but with experience it’s not much extra time,” he asserted.
Indeed, in a series of 452 Mayo Clinic maze III patients, the cross-clamp and cardiopulmonary bypass times were 52 and 73 minutes, respectively, for those undergoing an isolated maze III, compared with 73 and 86 minutes for patients whose maze III was done in conjunction with other procedures, most commonly mitral valve repair or replacement.
An underrecognized group of patients who benefit from a standalone cut-and-sew maze are those with tachycardia-induced cardiomyopathy marked by AF or atrial flutter, rapid uncontrolled ventricular response, a decreased left ventricular ejection fraction, and no associated valvular or congenital heart disease. In a series of 37 such patients identified and treated with a maze III operation at the Mayo Clinic, their average preoperative left ventricular ejection fraction of 43% improved to about 55% at discharge, a benefit sustained at last follow-up a median of 63 months later. The outcome was particularly impressive in the 11 patients with a severely depressed left ventricular ejection fraction averaging 31% preoperatively, which jumped to 53% at discharge (Ann Thorac Surg. 2006 Aug;82[2]:494-500).
“Their ejection fraction goes up when you control the tachycardia-induced cardiomyopathy,” he observed. “So reduced left ventricular ejection fraction may be an indication for surgery rather than a contraindication.”
Dr. Schaff emphasized that it’s important for cardiologists and surgeons not to overpromise what surgical ablation of AF can accomplish. The only randomized trial of surgical ablation of AF versus no ablation during mitral valve surgery, sponsored by the National Institutes of Health and Canadian Institutes of Health Research and carried out by the Cardiothoracic Surgical Trials Network, showed no significant between-group differences at 1 year in any of numerous quality of life measures, nor was there a survival benefit for ablation (N Engl J Med. 2015 Apr 9;372(15):1399-409).
“We must point out that there’s no indication that controlling atrial fibrillation has anything to do with improving survival. It has to do with symptomatic benefit and perhaps reducing risk of stroke,” he said.
Dr. Schaff reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – The term “maze procedure” for surgical ablation of atrial fibrillation is bandied about rather loosely these days, but as far as Hartzell V. Schaff, MD, is concerned, the operation of choice remains the classic cut-and-sew maze III procedure developed by James L. Cox, MD, while at Washington University, St. Louis.
“The classic Cox maze III, the cut-and-sew maze, is the best procedure for getting rid of atrial fibrillation and is in my view the gold standard. Some people argue that transmurality isn’t important, but it can occur because of gap lesions,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Unlike modifications of the Cox maze III – such as the mini maze or the maze IV, which utilizes radiofrequency energy or cryoablation to create scars in an effort to achieve pulmonary vein isolation – the maze III cannot be done as a minimally invasive procedure. After all, it requires making incisions in both atria, along with aortic cross-clamping and cardiopulmonary bypass. But it has a significantly higher long-term rate of freedom from recurrent atrial fibrillation (AF) than the other operations. And crucially, it enables the surgeon to readily obliterate the left atrial appendage.
“The most important thing when you do any surgical procedure for atrial fibrillation, I think, is getting rid of the left atrial appendage. When you do cut-and-sew maze, that’s done 100% of the time,” explained Dr. Schaff, professor of surgery at the Mayo Clinic in Rochester, Minn.
“We really have a lot of work left to do as surgeons in improving the outcome of surgery for atrial fibrillation. One of the things we as surgeons don’t do well is getting rid of the left atrial appendage. This ought to be done in every patient that has surgical ablation for atrial fibrillation,” according to the cardiothoracic surgeon.
And yet, he continued, in a series of nearly 87,000 patients with AF who underwent nonemergent cardiac surgery in the Society of Thoracic Surgeons database, 48.0% of whom underwent surgical ablation for AF, only 63.9% of those who had standalone ablation for lone AF got their left atrial appendage dealt with, compared with 86%-89% of those who underwent concomitant cardiac surgery, such as mitral valve repair or replacement (Ann Thorac Surg. 2017 Aug;104[2]:493-500).
“That’s awful, really. And the reason for that low left atrial appendage obliteration rate is this: For many of those patients who had surgery for lone atrial fibrillation, the surgeons were trying to do minimally invasive surgery, where they do pulmonary vein isolation on the right side, so they don’t have access to the left atrial appendage,” Dr. Schaff said.
“In the past,” he recalled, “we would ligate the left atrial appendage. Nowadays because of echocardiographic studies that show there’s persistent patency in a sizable percentage of patients, we amputate the left atrial appendage in almost all of the patients.”
The terminology surrounding surgical ablation for AF, in his view, has become rather confusing. “Most of you, when you refer a patient for surgical ablation for AF, the surgeons will just say they do a maze procedure,” Dr. Schaff cautioned. “Somehow, all of that [maze IV, mini maze] today is lumped together as a classic maze procedure, but it’s really not. We have different lesion sets and energy sources.”
And different outcomes as well. In a series of 1,189 adults who underwent surgical ablation for AF at the Mayo Clinic, of whom 44% had a biatrial cut-and-sew maze while the rest had surgical cryotherapy, radiofrequency ablation, or a combination of the two, the rate of freedom from AF 1 year post surgery was 85% with the cut-and-sew maze versus 71% with the alternatives. At 5 years or more, the rates were 78% and 52%, respectively. In a multivariate analysis, freedom from AF was independently associated with preoperative paroxysmal rather than permanent AF, performance of the classic maze III procedure, concomitant treatment of associated mitral valve disease, and younger age.
Moreover, rates of the major early postoperative complications – stroke, bleeding, and renal failure – were similar in the cut-and-sew maze III and other groups.
“So a lesser procedure doesn’t necessarily mean fewer complications,” Dr. Schaff noted.
One of the criticisms levied against the maze III is that it’s too much surgery for AF. But it’s actually relatively inexpensive because the disposables – suture, needles, scalpel – are those used in the commonly performed concomitant cardiac surgical procedures. “The Cox maze III does take extra time, but with experience it’s not much extra time,” he asserted.
Indeed, in a series of 452 Mayo Clinic maze III patients, the cross-clamp and cardiopulmonary bypass times were 52 and 73 minutes, respectively, for those undergoing an isolated maze III, compared with 73 and 86 minutes for patients whose maze III was done in conjunction with other procedures, most commonly mitral valve repair or replacement.
An underrecognized group of patients who benefit from a standalone cut-and-sew maze are those with tachycardia-induced cardiomyopathy marked by AF or atrial flutter, rapid uncontrolled ventricular response, a decreased left ventricular ejection fraction, and no associated valvular or congenital heart disease. In a series of 37 such patients identified and treated with a maze III operation at the Mayo Clinic, their average preoperative left ventricular ejection fraction of 43% improved to about 55% at discharge, a benefit sustained at last follow-up a median of 63 months later. The outcome was particularly impressive in the 11 patients with a severely depressed left ventricular ejection fraction averaging 31% preoperatively, which jumped to 53% at discharge (Ann Thorac Surg. 2006 Aug;82[2]:494-500).
“Their ejection fraction goes up when you control the tachycardia-induced cardiomyopathy,” he observed. “So reduced left ventricular ejection fraction may be an indication for surgery rather than a contraindication.”
Dr. Schaff emphasized that it’s important for cardiologists and surgeons not to overpromise what surgical ablation of AF can accomplish. The only randomized trial of surgical ablation of AF versus no ablation during mitral valve surgery, sponsored by the National Institutes of Health and Canadian Institutes of Health Research and carried out by the Cardiothoracic Surgical Trials Network, showed no significant between-group differences at 1 year in any of numerous quality of life measures, nor was there a survival benefit for ablation (N Engl J Med. 2015 Apr 9;372(15):1399-409).
“We must point out that there’s no indication that controlling atrial fibrillation has anything to do with improving survival. It has to do with symptomatic benefit and perhaps reducing risk of stroke,” he said.
Dr. Schaff reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – The term “maze procedure” for surgical ablation of atrial fibrillation is bandied about rather loosely these days, but as far as Hartzell V. Schaff, MD, is concerned, the operation of choice remains the classic cut-and-sew maze III procedure developed by James L. Cox, MD, while at Washington University, St. Louis.
“The classic Cox maze III, the cut-and-sew maze, is the best procedure for getting rid of atrial fibrillation and is in my view the gold standard. Some people argue that transmurality isn’t important, but it can occur because of gap lesions,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Unlike modifications of the Cox maze III – such as the mini maze or the maze IV, which utilizes radiofrequency energy or cryoablation to create scars in an effort to achieve pulmonary vein isolation – the maze III cannot be done as a minimally invasive procedure. After all, it requires making incisions in both atria, along with aortic cross-clamping and cardiopulmonary bypass. But it has a significantly higher long-term rate of freedom from recurrent atrial fibrillation (AF) than the other operations. And crucially, it enables the surgeon to readily obliterate the left atrial appendage.
“The most important thing when you do any surgical procedure for atrial fibrillation, I think, is getting rid of the left atrial appendage. When you do cut-and-sew maze, that’s done 100% of the time,” explained Dr. Schaff, professor of surgery at the Mayo Clinic in Rochester, Minn.
“We really have a lot of work left to do as surgeons in improving the outcome of surgery for atrial fibrillation. One of the things we as surgeons don’t do well is getting rid of the left atrial appendage. This ought to be done in every patient that has surgical ablation for atrial fibrillation,” according to the cardiothoracic surgeon.
And yet, he continued, in a series of nearly 87,000 patients with AF who underwent nonemergent cardiac surgery in the Society of Thoracic Surgeons database, 48.0% of whom underwent surgical ablation for AF, only 63.9% of those who had standalone ablation for lone AF got their left atrial appendage dealt with, compared with 86%-89% of those who underwent concomitant cardiac surgery, such as mitral valve repair or replacement (Ann Thorac Surg. 2017 Aug;104[2]:493-500).
“That’s awful, really. And the reason for that low left atrial appendage obliteration rate is this: For many of those patients who had surgery for lone atrial fibrillation, the surgeons were trying to do minimally invasive surgery, where they do pulmonary vein isolation on the right side, so they don’t have access to the left atrial appendage,” Dr. Schaff said.
“In the past,” he recalled, “we would ligate the left atrial appendage. Nowadays because of echocardiographic studies that show there’s persistent patency in a sizable percentage of patients, we amputate the left atrial appendage in almost all of the patients.”
The terminology surrounding surgical ablation for AF, in his view, has become rather confusing. “Most of you, when you refer a patient for surgical ablation for AF, the surgeons will just say they do a maze procedure,” Dr. Schaff cautioned. “Somehow, all of that [maze IV, mini maze] today is lumped together as a classic maze procedure, but it’s really not. We have different lesion sets and energy sources.”
And different outcomes as well. In a series of 1,189 adults who underwent surgical ablation for AF at the Mayo Clinic, of whom 44% had a biatrial cut-and-sew maze while the rest had surgical cryotherapy, radiofrequency ablation, or a combination of the two, the rate of freedom from AF 1 year post surgery was 85% with the cut-and-sew maze versus 71% with the alternatives. At 5 years or more, the rates were 78% and 52%, respectively. In a multivariate analysis, freedom from AF was independently associated with preoperative paroxysmal rather than permanent AF, performance of the classic maze III procedure, concomitant treatment of associated mitral valve disease, and younger age.
Moreover, rates of the major early postoperative complications – stroke, bleeding, and renal failure – were similar in the cut-and-sew maze III and other groups.
“So a lesser procedure doesn’t necessarily mean fewer complications,” Dr. Schaff noted.
One of the criticisms levied against the maze III is that it’s too much surgery for AF. But it’s actually relatively inexpensive because the disposables – suture, needles, scalpel – are those used in the commonly performed concomitant cardiac surgical procedures. “The Cox maze III does take extra time, but with experience it’s not much extra time,” he asserted.
Indeed, in a series of 452 Mayo Clinic maze III patients, the cross-clamp and cardiopulmonary bypass times were 52 and 73 minutes, respectively, for those undergoing an isolated maze III, compared with 73 and 86 minutes for patients whose maze III was done in conjunction with other procedures, most commonly mitral valve repair or replacement.
An underrecognized group of patients who benefit from a standalone cut-and-sew maze are those with tachycardia-induced cardiomyopathy marked by AF or atrial flutter, rapid uncontrolled ventricular response, a decreased left ventricular ejection fraction, and no associated valvular or congenital heart disease. In a series of 37 such patients identified and treated with a maze III operation at the Mayo Clinic, their average preoperative left ventricular ejection fraction of 43% improved to about 55% at discharge, a benefit sustained at last follow-up a median of 63 months later. The outcome was particularly impressive in the 11 patients with a severely depressed left ventricular ejection fraction averaging 31% preoperatively, which jumped to 53% at discharge (Ann Thorac Surg. 2006 Aug;82[2]:494-500).
“Their ejection fraction goes up when you control the tachycardia-induced cardiomyopathy,” he observed. “So reduced left ventricular ejection fraction may be an indication for surgery rather than a contraindication.”
Dr. Schaff emphasized that it’s important for cardiologists and surgeons not to overpromise what surgical ablation of AF can accomplish. The only randomized trial of surgical ablation of AF versus no ablation during mitral valve surgery, sponsored by the National Institutes of Health and Canadian Institutes of Health Research and carried out by the Cardiothoracic Surgical Trials Network, showed no significant between-group differences at 1 year in any of numerous quality of life measures, nor was there a survival benefit for ablation (N Engl J Med. 2015 Apr 9;372(15):1399-409).
“We must point out that there’s no indication that controlling atrial fibrillation has anything to do with improving survival. It has to do with symptomatic benefit and perhaps reducing risk of stroke,” he said.
Dr. Schaff reported having no financial conflicts regarding his presentation.
REPORTING FROM ACC SNOWMASS 2019
What cardiologists need to know about ARVC
SNOWMASS, COLO. – Electrophysiologist N.A. Mark Estes III, MD, has a piece of advice for his general cardiology colleagues regarding arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited arrhythmia syndrome that’s one of the most common causes of sudden death in athletes under the age of 40 years.
“When you have a patient with syncope and an ECG abnormality that suggests ARVC, you immediately restrict activity and immediately go on to imaging. And then it’s time to get that patient off to somebody who deals with these patients all the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
ARVC is thought to affect 1 in 5,000 people. It’s the cause of sudden death in roughly 5% of young athletes in the United States and 25% in Italy, with the disparity believed to be largely caused by underrecognition of the disease.
Dr. Estes was a coauthor of a 2015 international task force consensus statement on the treatment of ARVC (Eur Heart J. 2015 Dec 7;36[46]:3227-37). An updated report that incorporates much new information is due to be released in May 2019.
“The new guidelines are going to put some very clear limits on physical activity: Less than 7 METs [metabolic equivalents], which is about a brisk walk. Exercise is not good with ARVC,” said Dr. Estes, professor of medicine at the University of Pittsburgh.
Patients with ARVC absolutely must be restricted from participation in competitive sports, a step whose importance was demonstrated in the North American Multidisciplinary Study of ARVC, for which Dr. Estes was a coauthor. That study, too recent for inclusion in the 2015 task force consensus statement, showed that competitive sport was associated with a 100% increased risk of ventricular tachyarrhythmias and death, as well as earlier presentation with symptoms, compared with patients with ARVC who engaged in much less intense recreational athletic activity, who in turn didn’t have a risk level any different from inactive patients. That being said, however, the investigators also noted that the absolute risk of ventricular tachyarrhythmias or death remained high even in the inactive and recreational sports participants, at 23% by 2 years post diagnosis (Eur Heart J. 2015 Jul 14;36[27]:1735-43).
ARVC has three phases: An early concealed phase, with an associated high rate of syncope or sudden cardiac death; an intermediate phase marked by frequent arrhythmias; and a late phase involving cardiomyopathy and heart failure. Pathologically, the disease involves progressive loss of myocytes caused by abnormalities of plakoglobin and plakophilin, which Dr. Estes described as “essentially the glue that holds the sarcomeres together.” As myocytes are lost they are replaced by fibrofatty deposits, mostly in the right ventricle, creating a substrate for ventricular arrhythmias.
When to suspect ARVC?
“Anyone who has syncope with exertion automatically has a red flag because there is almost certainly something causing that event that’s potentially malignant,” according to the cardiologist.
An early, sensitive, and reasonably specific hallmark of ARVC on the 12-lead ECG is T wave inversion in right precordial leads V1, V2, and V3 or beyond. An epsilon wave – a small positive deflection at the end of the QRS complex – is present in about one in five patients with ARVC and is diagnostic of the condition.
“It’s an ECG you want to commit to memory. And when you see it, think ARVC,” Dr. Estes advised.
Abnormalities on MRI and 2D echocardiography include right ventricular enlargement and wall motion abnormalities, with left ventricular involvement becoming common in more advanced disease.
The detailed structural, electrographic, functional imaging, histologic, and clinical diagnostic criteria for ARVC, known as the 2010 Task Force Criteria, are readily available (Circulation. 2010 Apr 6;121[13]:1533-41). So are guidelines on genetic testing, which practitioners need to understand is now the standard of care for patients with ARVC and, in the event they are found to have a pathogenic mutation, in first-degree family members as well (Europace. 2011 Aug;13(8):1077-109).
“These days all you need to do is simply Google ‘syncope’ and ‘ARVC’ and you will get to the guidelines,” Dr. Estes advised. “It’s virtually impossible to keep up with all this information, but you should know how to access it and apply it in an individual patient. And learn the role of genetic testing. It’s very much an evolving area, quite mature for the long QT syndromes, but not a robust database for ARVC now. Yet there’s no doubt it’s going to be used more and more for diagnosis, risk stratification, and therapy of ARVC in the future.”
Once the diagnosis of ARVC is made in accordance with the 2010 Task Force Criteria, risk stratification and decision making about definitive therapy become paramount. The international task force consensus statement gives a Class I recommendation to implantable cardioverter defibrillator (ICD) therapy in high-risk ARVC patients, defined as those who’ve had a cardiac arrest, sustained ventricular tachycardia, or have severe right and/or left ventricular dysfunction. ICD therapy gets a Class IIa recommendation in those with at least one of the major risk factors: syncope, nonsustained ventricular tachycardia, and moderate ventricular dysfunction. For ARVC patients with one or more minor risk factors, which include frequent premature ventricular contractions and inducible ventricular tachycardia upon electrophysiological testing, the strength of the recommendation for ICD therapy drops to Class IIb, or “may be considered.” And for low-risk patients, those with confirmed ARVC but no phenotypic expressions of the disorder, the ICD recommendation is Class III, meaning nonindicated.
“There’s a very low threshold for putting in an ICD in patients with ARVC because if you eliminate the arrhythmic mortality, progression to heart failure needing advanced therapies or transplant is extremely rare as long as they’re restricted from athletics,” Dr. Estes said.
He reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.[email protected]
SNOWMASS, COLO. – Electrophysiologist N.A. Mark Estes III, MD, has a piece of advice for his general cardiology colleagues regarding arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited arrhythmia syndrome that’s one of the most common causes of sudden death in athletes under the age of 40 years.
“When you have a patient with syncope and an ECG abnormality that suggests ARVC, you immediately restrict activity and immediately go on to imaging. And then it’s time to get that patient off to somebody who deals with these patients all the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
ARVC is thought to affect 1 in 5,000 people. It’s the cause of sudden death in roughly 5% of young athletes in the United States and 25% in Italy, with the disparity believed to be largely caused by underrecognition of the disease.
Dr. Estes was a coauthor of a 2015 international task force consensus statement on the treatment of ARVC (Eur Heart J. 2015 Dec 7;36[46]:3227-37). An updated report that incorporates much new information is due to be released in May 2019.
“The new guidelines are going to put some very clear limits on physical activity: Less than 7 METs [metabolic equivalents], which is about a brisk walk. Exercise is not good with ARVC,” said Dr. Estes, professor of medicine at the University of Pittsburgh.
Patients with ARVC absolutely must be restricted from participation in competitive sports, a step whose importance was demonstrated in the North American Multidisciplinary Study of ARVC, for which Dr. Estes was a coauthor. That study, too recent for inclusion in the 2015 task force consensus statement, showed that competitive sport was associated with a 100% increased risk of ventricular tachyarrhythmias and death, as well as earlier presentation with symptoms, compared with patients with ARVC who engaged in much less intense recreational athletic activity, who in turn didn’t have a risk level any different from inactive patients. That being said, however, the investigators also noted that the absolute risk of ventricular tachyarrhythmias or death remained high even in the inactive and recreational sports participants, at 23% by 2 years post diagnosis (Eur Heart J. 2015 Jul 14;36[27]:1735-43).
ARVC has three phases: An early concealed phase, with an associated high rate of syncope or sudden cardiac death; an intermediate phase marked by frequent arrhythmias; and a late phase involving cardiomyopathy and heart failure. Pathologically, the disease involves progressive loss of myocytes caused by abnormalities of plakoglobin and plakophilin, which Dr. Estes described as “essentially the glue that holds the sarcomeres together.” As myocytes are lost they are replaced by fibrofatty deposits, mostly in the right ventricle, creating a substrate for ventricular arrhythmias.
When to suspect ARVC?
“Anyone who has syncope with exertion automatically has a red flag because there is almost certainly something causing that event that’s potentially malignant,” according to the cardiologist.
An early, sensitive, and reasonably specific hallmark of ARVC on the 12-lead ECG is T wave inversion in right precordial leads V1, V2, and V3 or beyond. An epsilon wave – a small positive deflection at the end of the QRS complex – is present in about one in five patients with ARVC and is diagnostic of the condition.
“It’s an ECG you want to commit to memory. And when you see it, think ARVC,” Dr. Estes advised.
Abnormalities on MRI and 2D echocardiography include right ventricular enlargement and wall motion abnormalities, with left ventricular involvement becoming common in more advanced disease.
The detailed structural, electrographic, functional imaging, histologic, and clinical diagnostic criteria for ARVC, known as the 2010 Task Force Criteria, are readily available (Circulation. 2010 Apr 6;121[13]:1533-41). So are guidelines on genetic testing, which practitioners need to understand is now the standard of care for patients with ARVC and, in the event they are found to have a pathogenic mutation, in first-degree family members as well (Europace. 2011 Aug;13(8):1077-109).
“These days all you need to do is simply Google ‘syncope’ and ‘ARVC’ and you will get to the guidelines,” Dr. Estes advised. “It’s virtually impossible to keep up with all this information, but you should know how to access it and apply it in an individual patient. And learn the role of genetic testing. It’s very much an evolving area, quite mature for the long QT syndromes, but not a robust database for ARVC now. Yet there’s no doubt it’s going to be used more and more for diagnosis, risk stratification, and therapy of ARVC in the future.”
Once the diagnosis of ARVC is made in accordance with the 2010 Task Force Criteria, risk stratification and decision making about definitive therapy become paramount. The international task force consensus statement gives a Class I recommendation to implantable cardioverter defibrillator (ICD) therapy in high-risk ARVC patients, defined as those who’ve had a cardiac arrest, sustained ventricular tachycardia, or have severe right and/or left ventricular dysfunction. ICD therapy gets a Class IIa recommendation in those with at least one of the major risk factors: syncope, nonsustained ventricular tachycardia, and moderate ventricular dysfunction. For ARVC patients with one or more minor risk factors, which include frequent premature ventricular contractions and inducible ventricular tachycardia upon electrophysiological testing, the strength of the recommendation for ICD therapy drops to Class IIb, or “may be considered.” And for low-risk patients, those with confirmed ARVC but no phenotypic expressions of the disorder, the ICD recommendation is Class III, meaning nonindicated.
“There’s a very low threshold for putting in an ICD in patients with ARVC because if you eliminate the arrhythmic mortality, progression to heart failure needing advanced therapies or transplant is extremely rare as long as they’re restricted from athletics,” Dr. Estes said.
He reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.[email protected]
SNOWMASS, COLO. – Electrophysiologist N.A. Mark Estes III, MD, has a piece of advice for his general cardiology colleagues regarding arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited arrhythmia syndrome that’s one of the most common causes of sudden death in athletes under the age of 40 years.
“When you have a patient with syncope and an ECG abnormality that suggests ARVC, you immediately restrict activity and immediately go on to imaging. And then it’s time to get that patient off to somebody who deals with these patients all the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
ARVC is thought to affect 1 in 5,000 people. It’s the cause of sudden death in roughly 5% of young athletes in the United States and 25% in Italy, with the disparity believed to be largely caused by underrecognition of the disease.
Dr. Estes was a coauthor of a 2015 international task force consensus statement on the treatment of ARVC (Eur Heart J. 2015 Dec 7;36[46]:3227-37). An updated report that incorporates much new information is due to be released in May 2019.
“The new guidelines are going to put some very clear limits on physical activity: Less than 7 METs [metabolic equivalents], which is about a brisk walk. Exercise is not good with ARVC,” said Dr. Estes, professor of medicine at the University of Pittsburgh.
Patients with ARVC absolutely must be restricted from participation in competitive sports, a step whose importance was demonstrated in the North American Multidisciplinary Study of ARVC, for which Dr. Estes was a coauthor. That study, too recent for inclusion in the 2015 task force consensus statement, showed that competitive sport was associated with a 100% increased risk of ventricular tachyarrhythmias and death, as well as earlier presentation with symptoms, compared with patients with ARVC who engaged in much less intense recreational athletic activity, who in turn didn’t have a risk level any different from inactive patients. That being said, however, the investigators also noted that the absolute risk of ventricular tachyarrhythmias or death remained high even in the inactive and recreational sports participants, at 23% by 2 years post diagnosis (Eur Heart J. 2015 Jul 14;36[27]:1735-43).
ARVC has three phases: An early concealed phase, with an associated high rate of syncope or sudden cardiac death; an intermediate phase marked by frequent arrhythmias; and a late phase involving cardiomyopathy and heart failure. Pathologically, the disease involves progressive loss of myocytes caused by abnormalities of plakoglobin and plakophilin, which Dr. Estes described as “essentially the glue that holds the sarcomeres together.” As myocytes are lost they are replaced by fibrofatty deposits, mostly in the right ventricle, creating a substrate for ventricular arrhythmias.
When to suspect ARVC?
“Anyone who has syncope with exertion automatically has a red flag because there is almost certainly something causing that event that’s potentially malignant,” according to the cardiologist.
An early, sensitive, and reasonably specific hallmark of ARVC on the 12-lead ECG is T wave inversion in right precordial leads V1, V2, and V3 or beyond. An epsilon wave – a small positive deflection at the end of the QRS complex – is present in about one in five patients with ARVC and is diagnostic of the condition.
“It’s an ECG you want to commit to memory. And when you see it, think ARVC,” Dr. Estes advised.
Abnormalities on MRI and 2D echocardiography include right ventricular enlargement and wall motion abnormalities, with left ventricular involvement becoming common in more advanced disease.
The detailed structural, electrographic, functional imaging, histologic, and clinical diagnostic criteria for ARVC, known as the 2010 Task Force Criteria, are readily available (Circulation. 2010 Apr 6;121[13]:1533-41). So are guidelines on genetic testing, which practitioners need to understand is now the standard of care for patients with ARVC and, in the event they are found to have a pathogenic mutation, in first-degree family members as well (Europace. 2011 Aug;13(8):1077-109).
“These days all you need to do is simply Google ‘syncope’ and ‘ARVC’ and you will get to the guidelines,” Dr. Estes advised. “It’s virtually impossible to keep up with all this information, but you should know how to access it and apply it in an individual patient. And learn the role of genetic testing. It’s very much an evolving area, quite mature for the long QT syndromes, but not a robust database for ARVC now. Yet there’s no doubt it’s going to be used more and more for diagnosis, risk stratification, and therapy of ARVC in the future.”
Once the diagnosis of ARVC is made in accordance with the 2010 Task Force Criteria, risk stratification and decision making about definitive therapy become paramount. The international task force consensus statement gives a Class I recommendation to implantable cardioverter defibrillator (ICD) therapy in high-risk ARVC patients, defined as those who’ve had a cardiac arrest, sustained ventricular tachycardia, or have severe right and/or left ventricular dysfunction. ICD therapy gets a Class IIa recommendation in those with at least one of the major risk factors: syncope, nonsustained ventricular tachycardia, and moderate ventricular dysfunction. For ARVC patients with one or more minor risk factors, which include frequent premature ventricular contractions and inducible ventricular tachycardia upon electrophysiological testing, the strength of the recommendation for ICD therapy drops to Class IIb, or “may be considered.” And for low-risk patients, those with confirmed ARVC but no phenotypic expressions of the disorder, the ICD recommendation is Class III, meaning nonindicated.
“There’s a very low threshold for putting in an ICD in patients with ARVC because if you eliminate the arrhythmic mortality, progression to heart failure needing advanced therapies or transplant is extremely rare as long as they’re restricted from athletics,” Dr. Estes said.
He reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.[email protected]
REPORTING FROM ACC SNOWMASS 2019