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Discharge within 24 hours of PCI can be safe in select STEMI
Highly selected low-risk patients can be safely sent home about 24 hours after successful percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) when supported by intense, multidisciplinary virtual follow-up, a prospective study suggests for the first time.
The risk for major adverse cardiac events (MACE) in STEMI patients following an early hospital discharge (EHD) pathway was similar at 9 months to that seen for propensity-matched historic control subjects who met the same EHD criteria but were discharged later than 48 hours.
The stay in almost half (48%) the early discharge group was 24 hours or less, according to the study, published Dec. 13 in the Journal of the American College of Cardiology.
“We’ve shown that if we use appropriate risk criteria and instigate the appropriate, safe follow-up that it’s safe to select and discharge low-risk patients at an earlier time period, such as 24 hours,” senior author Daniel A. Jones, PhD, Barts Heart Centre, London, this news organization.
“Obviously, it’s one center in one city in the world,” he said. “Whether it’s applicable at other heart site centers, I believe it is, but I think we need more data to be able to change guidelines.”
Current European Society of Cardiology guidelines say that select patients should be considered for early discharge 48 to 72 hours after STEMI, but the COVID-19 pandemic incentivized the team to try and push that window.
“The COVID pandemic essentially brought a focus on resources, on minimizing the risk to our patient population in terms of catching COVID within hospital,” he said. “It became clear that to maintain the heart site service, we probably needed to get people out a bit quicker than we did before, so we came up with this pathway.”
Between March 2020 and June 2021, 600 patients presenting with STEMI were entered into the EHD pathway if they met the following pre-existing criteria for 48- to 72-hour discharge:
- Left ventricular ejection fraction 40% or greater
- Successful primary PCI with TIMI flow grade 3
- Absence of bystander disease requiring inpatient revascularization
- No recurrent ischemic symptoms
- No heart failure
- No significant arrhythmias
- No hemodynamic instability
- No significant comorbidity
- Suitable social circumstances for early discharge
The patients were given cardiac rehabilitation counseling over the phone within 48 hours and blood pressure machines if not available at home. At weeks 2 and 8, they spoke virtually with a dedicated cardiology advanced care practitioner who up-titrated medications and answered any questions. At week 12, they were seen by an interventional cardiologist or at a high-risk prevention clinic.
Their mean age was 59.2 years, 86% were male, the median symptom-to-balloon time was 80 minutes, and median door-to-balloon time was 50 minutes.
The early discharge patients were compared with 700 historic control subjects who met the EHD criteria and were discharged after 48 hours from Oct. 2018 to June 2021 and 560 patients discharged on standard-care pathways between April 2020 and June 2021.
Those discharged after 48 hours were more likely to have an anterior MI, multivessel disease, and multivessel PCI.
Comparable outcomes
The median length of stay was 24.6 hours (minimum 17 hours, maximum 40 hours) for the EHD group, 56.1 hours for historic control subjects, and 78.9 hours for the standard-care group.
The introduction of the EHD pathway significantly reduced the overall length of stay for all STEMI patients compared with the pre-pathway period of Oct. 2018 to March 2020 (median, 3 vs. 2 days; P < .0001).
Length of stay varied among patients; however, 420 patients stayed 1 less night in the hospital with the remaining patients staying about 8 to 12 fewer hours, resulting in approximate savings of £450,000, the authors note.
Over a median follow-up of 271 days, there were no cardiovascular deaths, two deaths from COVID-19, and a MACE rate of 1.2% (two deaths, three unscheduled revascularizations, and two further MI presentations) in the EHD group. That compares with a 0.7% mortality and 1.9% rate of MACE among historic control subjects, neither of which were significantly different.
There was also no difference in mortality (0.34% vs. 0.69%; P = .410) or MACE (1.2% vs. 1.9%; P = .342) among 560 pairs of propensity-matched EHD patients and historic control subjects.
Mortality was 4.1% in the standard-care group; cardiovascular mortality was 2.2%, and the rate of MACE was 8.6%.
When patients were surveyed, 85% were “satisfied” or “very satisfied” with the EHD pathway, whereas 73% of control and standard-care patients were satisfied with their care. Three-fourths of EHD patients also reported saving money and 62.5% saved time off work because of the virtual follow-up.
Judgment calls
“They didn’t really tell us much about the patients who didn’t qualify into this ultra–low-risk group but, obviously, it’s highly selected,” Cindy Grines, MD, Northside Hospital Cardiovascular Institute, Lawrenceville, Georgia, said in an interview. “In the U.S., you don’t get those chest pain onset-to-reperfusion in 80 minutes. So that was really kind of shocking.”
It also suggests that early discharge was applied to patients who may have had minimal myocardial damage from the STEMI, she suggested. “Even in their own hospital system, a lot of patients who met the criteria on paper were kept longer than 48 hours. So a lot of it’s a judgment call.”
Additional red flags where physicians may overrule the early discharge protocol are very late perfusion, advanced age, severe renal insufficiency, profound anemia, cardiac arrest requiring more than brief resuscitation, bleeding complications, or symptomatic coronavirus, Dr. Grines and J. Jeffrey Marshall, MD, also from Northside, observe in an accompanying editorial.
About 60% of patients were suitable for the EHD pathway, Dr. Jones said. “Typically, they are quite low risk, but we still had four in 10 anterior infarct, and about 25% had left ventricular function between 40% and 45%. So even though the majority are low risk, there are patients in there that you would consider to have had a decent infarct.”
“I think this is applicable to patients at most centers, and probably anywhere between a third to a fifth of all patients presenting to heart centers would be suitable for this discharge pathway,” he said.
Dr. Grines said the pathway is “definitely feasible” but there aren’t enough patients studied to know with 100% certainty whether it’s safe. A single observational study also isn’t enough to change guidelines, which in the United States do not comment on length of stay.
“In the ultra-low-risk patients – such as the ones where you got them in very early and you almost aborted the infarct or if it was a very small infarct – you can kind of treat them like an unstable angina patient, where you can do the PCI and potentially discharge them in 24 hours,” Dr. Grines said. “I think most of us might agree on that.”
“The other thing you have to weigh is the risk/benefit ratio,” she said. “If you have no beds available, you end up rationing care to some extent. So if you have a patient that’s otherwise doing well after a very small MI and have an emergency room full of people that need to be admitted and they’re sicker, then you end up making those judgment calls.”
Dr. Jones pointed out that current guidelines are based largely on observational data and that the team is planning to pilot the EHD pathway at five to 10 centers around the United Kingdom or potentially in Europe or the United States.
“This is an area where a [randomized controlled trial] RCT would be expensive, whereas a well-coordinated multicenter registry would probably provide enough information to change guidelines,” he said. “We’re not suggesting that every STEMI patient is suitable, but people that are low risk that you would already be considering for early discharge I think can go a bit quicker.”
Dr. Jones has received funding from the Barts Charity and financial support for blood pressure machines from the Barts Guild. First author Krishnaraj Rathod has received funding from the National Institute for Health and Research in the form of an Academic Clinical Lectureship. All other authors, Dr. Grines, and Dr. Marshall report having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Highly selected low-risk patients can be safely sent home about 24 hours after successful percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) when supported by intense, multidisciplinary virtual follow-up, a prospective study suggests for the first time.
The risk for major adverse cardiac events (MACE) in STEMI patients following an early hospital discharge (EHD) pathway was similar at 9 months to that seen for propensity-matched historic control subjects who met the same EHD criteria but were discharged later than 48 hours.
The stay in almost half (48%) the early discharge group was 24 hours or less, according to the study, published Dec. 13 in the Journal of the American College of Cardiology.
“We’ve shown that if we use appropriate risk criteria and instigate the appropriate, safe follow-up that it’s safe to select and discharge low-risk patients at an earlier time period, such as 24 hours,” senior author Daniel A. Jones, PhD, Barts Heart Centre, London, this news organization.
“Obviously, it’s one center in one city in the world,” he said. “Whether it’s applicable at other heart site centers, I believe it is, but I think we need more data to be able to change guidelines.”
Current European Society of Cardiology guidelines say that select patients should be considered for early discharge 48 to 72 hours after STEMI, but the COVID-19 pandemic incentivized the team to try and push that window.
“The COVID pandemic essentially brought a focus on resources, on minimizing the risk to our patient population in terms of catching COVID within hospital,” he said. “It became clear that to maintain the heart site service, we probably needed to get people out a bit quicker than we did before, so we came up with this pathway.”
Between March 2020 and June 2021, 600 patients presenting with STEMI were entered into the EHD pathway if they met the following pre-existing criteria for 48- to 72-hour discharge:
- Left ventricular ejection fraction 40% or greater
- Successful primary PCI with TIMI flow grade 3
- Absence of bystander disease requiring inpatient revascularization
- No recurrent ischemic symptoms
- No heart failure
- No significant arrhythmias
- No hemodynamic instability
- No significant comorbidity
- Suitable social circumstances for early discharge
The patients were given cardiac rehabilitation counseling over the phone within 48 hours and blood pressure machines if not available at home. At weeks 2 and 8, they spoke virtually with a dedicated cardiology advanced care practitioner who up-titrated medications and answered any questions. At week 12, they were seen by an interventional cardiologist or at a high-risk prevention clinic.
Their mean age was 59.2 years, 86% were male, the median symptom-to-balloon time was 80 minutes, and median door-to-balloon time was 50 minutes.
The early discharge patients were compared with 700 historic control subjects who met the EHD criteria and were discharged after 48 hours from Oct. 2018 to June 2021 and 560 patients discharged on standard-care pathways between April 2020 and June 2021.
Those discharged after 48 hours were more likely to have an anterior MI, multivessel disease, and multivessel PCI.
Comparable outcomes
The median length of stay was 24.6 hours (minimum 17 hours, maximum 40 hours) for the EHD group, 56.1 hours for historic control subjects, and 78.9 hours for the standard-care group.
The introduction of the EHD pathway significantly reduced the overall length of stay for all STEMI patients compared with the pre-pathway period of Oct. 2018 to March 2020 (median, 3 vs. 2 days; P < .0001).
Length of stay varied among patients; however, 420 patients stayed 1 less night in the hospital with the remaining patients staying about 8 to 12 fewer hours, resulting in approximate savings of £450,000, the authors note.
Over a median follow-up of 271 days, there were no cardiovascular deaths, two deaths from COVID-19, and a MACE rate of 1.2% (two deaths, three unscheduled revascularizations, and two further MI presentations) in the EHD group. That compares with a 0.7% mortality and 1.9% rate of MACE among historic control subjects, neither of which were significantly different.
There was also no difference in mortality (0.34% vs. 0.69%; P = .410) or MACE (1.2% vs. 1.9%; P = .342) among 560 pairs of propensity-matched EHD patients and historic control subjects.
Mortality was 4.1% in the standard-care group; cardiovascular mortality was 2.2%, and the rate of MACE was 8.6%.
When patients were surveyed, 85% were “satisfied” or “very satisfied” with the EHD pathway, whereas 73% of control and standard-care patients were satisfied with their care. Three-fourths of EHD patients also reported saving money and 62.5% saved time off work because of the virtual follow-up.
Judgment calls
“They didn’t really tell us much about the patients who didn’t qualify into this ultra–low-risk group but, obviously, it’s highly selected,” Cindy Grines, MD, Northside Hospital Cardiovascular Institute, Lawrenceville, Georgia, said in an interview. “In the U.S., you don’t get those chest pain onset-to-reperfusion in 80 minutes. So that was really kind of shocking.”
It also suggests that early discharge was applied to patients who may have had minimal myocardial damage from the STEMI, she suggested. “Even in their own hospital system, a lot of patients who met the criteria on paper were kept longer than 48 hours. So a lot of it’s a judgment call.”
Additional red flags where physicians may overrule the early discharge protocol are very late perfusion, advanced age, severe renal insufficiency, profound anemia, cardiac arrest requiring more than brief resuscitation, bleeding complications, or symptomatic coronavirus, Dr. Grines and J. Jeffrey Marshall, MD, also from Northside, observe in an accompanying editorial.
About 60% of patients were suitable for the EHD pathway, Dr. Jones said. “Typically, they are quite low risk, but we still had four in 10 anterior infarct, and about 25% had left ventricular function between 40% and 45%. So even though the majority are low risk, there are patients in there that you would consider to have had a decent infarct.”
“I think this is applicable to patients at most centers, and probably anywhere between a third to a fifth of all patients presenting to heart centers would be suitable for this discharge pathway,” he said.
Dr. Grines said the pathway is “definitely feasible” but there aren’t enough patients studied to know with 100% certainty whether it’s safe. A single observational study also isn’t enough to change guidelines, which in the United States do not comment on length of stay.
“In the ultra-low-risk patients – such as the ones where you got them in very early and you almost aborted the infarct or if it was a very small infarct – you can kind of treat them like an unstable angina patient, where you can do the PCI and potentially discharge them in 24 hours,” Dr. Grines said. “I think most of us might agree on that.”
“The other thing you have to weigh is the risk/benefit ratio,” she said. “If you have no beds available, you end up rationing care to some extent. So if you have a patient that’s otherwise doing well after a very small MI and have an emergency room full of people that need to be admitted and they’re sicker, then you end up making those judgment calls.”
Dr. Jones pointed out that current guidelines are based largely on observational data and that the team is planning to pilot the EHD pathway at five to 10 centers around the United Kingdom or potentially in Europe or the United States.
“This is an area where a [randomized controlled trial] RCT would be expensive, whereas a well-coordinated multicenter registry would probably provide enough information to change guidelines,” he said. “We’re not suggesting that every STEMI patient is suitable, but people that are low risk that you would already be considering for early discharge I think can go a bit quicker.”
Dr. Jones has received funding from the Barts Charity and financial support for blood pressure machines from the Barts Guild. First author Krishnaraj Rathod has received funding from the National Institute for Health and Research in the form of an Academic Clinical Lectureship. All other authors, Dr. Grines, and Dr. Marshall report having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Highly selected low-risk patients can be safely sent home about 24 hours after successful percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) when supported by intense, multidisciplinary virtual follow-up, a prospective study suggests for the first time.
The risk for major adverse cardiac events (MACE) in STEMI patients following an early hospital discharge (EHD) pathway was similar at 9 months to that seen for propensity-matched historic control subjects who met the same EHD criteria but were discharged later than 48 hours.
The stay in almost half (48%) the early discharge group was 24 hours or less, according to the study, published Dec. 13 in the Journal of the American College of Cardiology.
“We’ve shown that if we use appropriate risk criteria and instigate the appropriate, safe follow-up that it’s safe to select and discharge low-risk patients at an earlier time period, such as 24 hours,” senior author Daniel A. Jones, PhD, Barts Heart Centre, London, this news organization.
“Obviously, it’s one center in one city in the world,” he said. “Whether it’s applicable at other heart site centers, I believe it is, but I think we need more data to be able to change guidelines.”
Current European Society of Cardiology guidelines say that select patients should be considered for early discharge 48 to 72 hours after STEMI, but the COVID-19 pandemic incentivized the team to try and push that window.
“The COVID pandemic essentially brought a focus on resources, on minimizing the risk to our patient population in terms of catching COVID within hospital,” he said. “It became clear that to maintain the heart site service, we probably needed to get people out a bit quicker than we did before, so we came up with this pathway.”
Between March 2020 and June 2021, 600 patients presenting with STEMI were entered into the EHD pathway if they met the following pre-existing criteria for 48- to 72-hour discharge:
- Left ventricular ejection fraction 40% or greater
- Successful primary PCI with TIMI flow grade 3
- Absence of bystander disease requiring inpatient revascularization
- No recurrent ischemic symptoms
- No heart failure
- No significant arrhythmias
- No hemodynamic instability
- No significant comorbidity
- Suitable social circumstances for early discharge
The patients were given cardiac rehabilitation counseling over the phone within 48 hours and blood pressure machines if not available at home. At weeks 2 and 8, they spoke virtually with a dedicated cardiology advanced care practitioner who up-titrated medications and answered any questions. At week 12, they were seen by an interventional cardiologist or at a high-risk prevention clinic.
Their mean age was 59.2 years, 86% were male, the median symptom-to-balloon time was 80 minutes, and median door-to-balloon time was 50 minutes.
The early discharge patients were compared with 700 historic control subjects who met the EHD criteria and were discharged after 48 hours from Oct. 2018 to June 2021 and 560 patients discharged on standard-care pathways between April 2020 and June 2021.
Those discharged after 48 hours were more likely to have an anterior MI, multivessel disease, and multivessel PCI.
Comparable outcomes
The median length of stay was 24.6 hours (minimum 17 hours, maximum 40 hours) for the EHD group, 56.1 hours for historic control subjects, and 78.9 hours for the standard-care group.
The introduction of the EHD pathway significantly reduced the overall length of stay for all STEMI patients compared with the pre-pathway period of Oct. 2018 to March 2020 (median, 3 vs. 2 days; P < .0001).
Length of stay varied among patients; however, 420 patients stayed 1 less night in the hospital with the remaining patients staying about 8 to 12 fewer hours, resulting in approximate savings of £450,000, the authors note.
Over a median follow-up of 271 days, there were no cardiovascular deaths, two deaths from COVID-19, and a MACE rate of 1.2% (two deaths, three unscheduled revascularizations, and two further MI presentations) in the EHD group. That compares with a 0.7% mortality and 1.9% rate of MACE among historic control subjects, neither of which were significantly different.
There was also no difference in mortality (0.34% vs. 0.69%; P = .410) or MACE (1.2% vs. 1.9%; P = .342) among 560 pairs of propensity-matched EHD patients and historic control subjects.
Mortality was 4.1% in the standard-care group; cardiovascular mortality was 2.2%, and the rate of MACE was 8.6%.
When patients were surveyed, 85% were “satisfied” or “very satisfied” with the EHD pathway, whereas 73% of control and standard-care patients were satisfied with their care. Three-fourths of EHD patients also reported saving money and 62.5% saved time off work because of the virtual follow-up.
Judgment calls
“They didn’t really tell us much about the patients who didn’t qualify into this ultra–low-risk group but, obviously, it’s highly selected,” Cindy Grines, MD, Northside Hospital Cardiovascular Institute, Lawrenceville, Georgia, said in an interview. “In the U.S., you don’t get those chest pain onset-to-reperfusion in 80 minutes. So that was really kind of shocking.”
It also suggests that early discharge was applied to patients who may have had minimal myocardial damage from the STEMI, she suggested. “Even in their own hospital system, a lot of patients who met the criteria on paper were kept longer than 48 hours. So a lot of it’s a judgment call.”
Additional red flags where physicians may overrule the early discharge protocol are very late perfusion, advanced age, severe renal insufficiency, profound anemia, cardiac arrest requiring more than brief resuscitation, bleeding complications, or symptomatic coronavirus, Dr. Grines and J. Jeffrey Marshall, MD, also from Northside, observe in an accompanying editorial.
About 60% of patients were suitable for the EHD pathway, Dr. Jones said. “Typically, they are quite low risk, but we still had four in 10 anterior infarct, and about 25% had left ventricular function between 40% and 45%. So even though the majority are low risk, there are patients in there that you would consider to have had a decent infarct.”
“I think this is applicable to patients at most centers, and probably anywhere between a third to a fifth of all patients presenting to heart centers would be suitable for this discharge pathway,” he said.
Dr. Grines said the pathway is “definitely feasible” but there aren’t enough patients studied to know with 100% certainty whether it’s safe. A single observational study also isn’t enough to change guidelines, which in the United States do not comment on length of stay.
“In the ultra-low-risk patients – such as the ones where you got them in very early and you almost aborted the infarct or if it was a very small infarct – you can kind of treat them like an unstable angina patient, where you can do the PCI and potentially discharge them in 24 hours,” Dr. Grines said. “I think most of us might agree on that.”
“The other thing you have to weigh is the risk/benefit ratio,” she said. “If you have no beds available, you end up rationing care to some extent. So if you have a patient that’s otherwise doing well after a very small MI and have an emergency room full of people that need to be admitted and they’re sicker, then you end up making those judgment calls.”
Dr. Jones pointed out that current guidelines are based largely on observational data and that the team is planning to pilot the EHD pathway at five to 10 centers around the United Kingdom or potentially in Europe or the United States.
“This is an area where a [randomized controlled trial] RCT would be expensive, whereas a well-coordinated multicenter registry would probably provide enough information to change guidelines,” he said. “We’re not suggesting that every STEMI patient is suitable, but people that are low risk that you would already be considering for early discharge I think can go a bit quicker.”
Dr. Jones has received funding from the Barts Charity and financial support for blood pressure machines from the Barts Guild. First author Krishnaraj Rathod has received funding from the National Institute for Health and Research in the form of an Academic Clinical Lectureship. All other authors, Dr. Grines, and Dr. Marshall report having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
ACC, AHA issue new coronary revascularization guideline
Clinicians should approach decisions regarding coronary revascularization based on clinical indications without an eye toward sex, race, or ethnicity, advises a joint clinical practice guideline released Dec. 8 by the American Heart Association and American College of Cardiology.
The new class 1 recommendation leads off the 109-page document and reflects evidence demonstrating that revascularization is equally beneficial for all patients. Still, studies show that women and non-White patients are less likely to receive reperfusion therapy or revascularization.
“This was extremely important to all the committee members because of all of the disparities that have been documented not only in diagnosis but [in] the care provided to underrepresented minorities, women, and other ethnic groups,” said Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair.
“We wanted to make it clear right at the beginning of the document that these guidelines apply to everyone, and we want it to be known that care should be the same for everyone,” she said in an interview.
The guideline was simultaneously published Dec. 9, 2021, in the journal Circulation and the Journal of the American College of Cardiology.
It updates and consolidates the ACC/AHA 2011 coronary artery bypass surgery (CABG) guideline and the ACC/AHA/Society for Cardiovascular Angiography and Interventions 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.
The new document emphasizes in a class 1 recommendation the importance of the multidisciplinary heart team in patients with coronary artery disease (CAD) where the best treatment strategy is unclear. But it also stresses that treatment decisions should be patient centered – taking into account patient preferences and goals, cultural beliefs, health literacy, and social determinants of cardiovascular health – and made in collaboration with the patient’s support system.
“Oftentimes we recommend a strategy of revascularization that may not be what the patient wants or hasn’t taken into account the patient’s preferences and also the family members,” Dr. Lawson said. “So we felt that was very important.”
Patients should also be provided with available evidence for various treatment options, including risks and benefits of each option, for informed consent. The two new class 1 recommendations are highlighted in a figure illustrating the shared decision-making algorithm that, by design, features a female clinician and Black patient.
“We spent 2 years debating the best revascularization strategies and we’re considered experts in the field – but when we talk to our patients, they really don’t know the benefits and risks,” she said. “In order to translate it to the layperson in basic terms, it’s important to say, ‘If you choose this option, you will likely live longer’ rather than using the jargon.”
DAPT, staged PCI, stable IHD
Among the top 10 take-home messages highlighted by the authors is a 2a recommendation that 1-3 months of dual antiplatelet therapy (DAPT) after PCI with a transition to P2Y12 inhibitor monotherapy is “reasonable” in selected patients to reduce the risk of bleeding events. Previous recommendations called for 6 or 12 months of DAPT.
“We really respect all of the clinical trials that came out showing that a shorter duration of DAPT is not inferior in terms of ischemic events but less bleeding, yet I don’t know how many clinicians are actually just using 3 months of DAPT followed by P2Y12 monotherapy,” guideline committee vice chair Jacqueline Tamis-Holland, MD, professor of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an interview. “So while it’s not a big, glaring giant recommendation, I think it will change a lot of practice.”
Similarly, she suggested that practice may shift as a result of a class 1 recommendation for staged PCI of a significantly stenosed nonculprit artery to reduce the risk for death or MI in selected hemodynamically stable patients presenting with ST-segment elevation MI and multivessel disease. “When you survey physicians, 75% of them do staged PCI but I think there will probably be more of an approach to staged PCI, as opposed to doing multivessel PCI at the time of primary PCI.”
Newer evidence from meta-analyses and the landmark ISCHEMIA trial showing no advantage of CABG over medical therapy in stable ischemic heart disease is reflected in a new class 2b recommendation – downgraded from class 1 in 2011 – that CABG “may be reasonable” to improve survival in stable patients with triple-vessel CAD.
The writing committee concluded that the ability of PCI to improve survival, compared with medical therapy in multivessel CAD “remains uncertain.”
Other recommendations likely to be of interest are that the radial artery is preferred, after the left internal mammary artery, as a surgical revascularization conduit over use of a saphenous vein conduit. Benefits include superior patency, fewer adverse cardiac events, and improved survival, the committee noted.
The radial artery is also recommended (class 1) in patients undergoing PCI who have acute coronary syndromes or stable ischemic heart disease to reduce bleeding and vascular complications compared with a femoral approach.
“Having both new radial recommendations sort of makes a bit of tension because the interventionalist is going to want to use the radial artery, but also the surgeon is too,” observed Dr. Tamis-Holland. “We see that in our own practice, so we try to have a collaborative approach to the patient to say: ‘Maybe do the cardiac cath in the dominant radial and then we can use the nondominant radial for a bypass conduit,’ but using both for each revascularization strategy will benefit the patient.
“So, we just have to remember that we’re going to talk together as a heart team and try to make the best decisions for each patient.”
A version of this article first appeared on Medscape.com.
Clinicians should approach decisions regarding coronary revascularization based on clinical indications without an eye toward sex, race, or ethnicity, advises a joint clinical practice guideline released Dec. 8 by the American Heart Association and American College of Cardiology.
The new class 1 recommendation leads off the 109-page document and reflects evidence demonstrating that revascularization is equally beneficial for all patients. Still, studies show that women and non-White patients are less likely to receive reperfusion therapy or revascularization.
“This was extremely important to all the committee members because of all of the disparities that have been documented not only in diagnosis but [in] the care provided to underrepresented minorities, women, and other ethnic groups,” said Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair.
“We wanted to make it clear right at the beginning of the document that these guidelines apply to everyone, and we want it to be known that care should be the same for everyone,” she said in an interview.
The guideline was simultaneously published Dec. 9, 2021, in the journal Circulation and the Journal of the American College of Cardiology.
It updates and consolidates the ACC/AHA 2011 coronary artery bypass surgery (CABG) guideline and the ACC/AHA/Society for Cardiovascular Angiography and Interventions 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.
The new document emphasizes in a class 1 recommendation the importance of the multidisciplinary heart team in patients with coronary artery disease (CAD) where the best treatment strategy is unclear. But it also stresses that treatment decisions should be patient centered – taking into account patient preferences and goals, cultural beliefs, health literacy, and social determinants of cardiovascular health – and made in collaboration with the patient’s support system.
“Oftentimes we recommend a strategy of revascularization that may not be what the patient wants or hasn’t taken into account the patient’s preferences and also the family members,” Dr. Lawson said. “So we felt that was very important.”
Patients should also be provided with available evidence for various treatment options, including risks and benefits of each option, for informed consent. The two new class 1 recommendations are highlighted in a figure illustrating the shared decision-making algorithm that, by design, features a female clinician and Black patient.
“We spent 2 years debating the best revascularization strategies and we’re considered experts in the field – but when we talk to our patients, they really don’t know the benefits and risks,” she said. “In order to translate it to the layperson in basic terms, it’s important to say, ‘If you choose this option, you will likely live longer’ rather than using the jargon.”
DAPT, staged PCI, stable IHD
Among the top 10 take-home messages highlighted by the authors is a 2a recommendation that 1-3 months of dual antiplatelet therapy (DAPT) after PCI with a transition to P2Y12 inhibitor monotherapy is “reasonable” in selected patients to reduce the risk of bleeding events. Previous recommendations called for 6 or 12 months of DAPT.
“We really respect all of the clinical trials that came out showing that a shorter duration of DAPT is not inferior in terms of ischemic events but less bleeding, yet I don’t know how many clinicians are actually just using 3 months of DAPT followed by P2Y12 monotherapy,” guideline committee vice chair Jacqueline Tamis-Holland, MD, professor of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an interview. “So while it’s not a big, glaring giant recommendation, I think it will change a lot of practice.”
Similarly, she suggested that practice may shift as a result of a class 1 recommendation for staged PCI of a significantly stenosed nonculprit artery to reduce the risk for death or MI in selected hemodynamically stable patients presenting with ST-segment elevation MI and multivessel disease. “When you survey physicians, 75% of them do staged PCI but I think there will probably be more of an approach to staged PCI, as opposed to doing multivessel PCI at the time of primary PCI.”
Newer evidence from meta-analyses and the landmark ISCHEMIA trial showing no advantage of CABG over medical therapy in stable ischemic heart disease is reflected in a new class 2b recommendation – downgraded from class 1 in 2011 – that CABG “may be reasonable” to improve survival in stable patients with triple-vessel CAD.
The writing committee concluded that the ability of PCI to improve survival, compared with medical therapy in multivessel CAD “remains uncertain.”
Other recommendations likely to be of interest are that the radial artery is preferred, after the left internal mammary artery, as a surgical revascularization conduit over use of a saphenous vein conduit. Benefits include superior patency, fewer adverse cardiac events, and improved survival, the committee noted.
The radial artery is also recommended (class 1) in patients undergoing PCI who have acute coronary syndromes or stable ischemic heart disease to reduce bleeding and vascular complications compared with a femoral approach.
“Having both new radial recommendations sort of makes a bit of tension because the interventionalist is going to want to use the radial artery, but also the surgeon is too,” observed Dr. Tamis-Holland. “We see that in our own practice, so we try to have a collaborative approach to the patient to say: ‘Maybe do the cardiac cath in the dominant radial and then we can use the nondominant radial for a bypass conduit,’ but using both for each revascularization strategy will benefit the patient.
“So, we just have to remember that we’re going to talk together as a heart team and try to make the best decisions for each patient.”
A version of this article first appeared on Medscape.com.
Clinicians should approach decisions regarding coronary revascularization based on clinical indications without an eye toward sex, race, or ethnicity, advises a joint clinical practice guideline released Dec. 8 by the American Heart Association and American College of Cardiology.
The new class 1 recommendation leads off the 109-page document and reflects evidence demonstrating that revascularization is equally beneficial for all patients. Still, studies show that women and non-White patients are less likely to receive reperfusion therapy or revascularization.
“This was extremely important to all the committee members because of all of the disparities that have been documented not only in diagnosis but [in] the care provided to underrepresented minorities, women, and other ethnic groups,” said Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair.
“We wanted to make it clear right at the beginning of the document that these guidelines apply to everyone, and we want it to be known that care should be the same for everyone,” she said in an interview.
The guideline was simultaneously published Dec. 9, 2021, in the journal Circulation and the Journal of the American College of Cardiology.
It updates and consolidates the ACC/AHA 2011 coronary artery bypass surgery (CABG) guideline and the ACC/AHA/Society for Cardiovascular Angiography and Interventions 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.
The new document emphasizes in a class 1 recommendation the importance of the multidisciplinary heart team in patients with coronary artery disease (CAD) where the best treatment strategy is unclear. But it also stresses that treatment decisions should be patient centered – taking into account patient preferences and goals, cultural beliefs, health literacy, and social determinants of cardiovascular health – and made in collaboration with the patient’s support system.
“Oftentimes we recommend a strategy of revascularization that may not be what the patient wants or hasn’t taken into account the patient’s preferences and also the family members,” Dr. Lawson said. “So we felt that was very important.”
Patients should also be provided with available evidence for various treatment options, including risks and benefits of each option, for informed consent. The two new class 1 recommendations are highlighted in a figure illustrating the shared decision-making algorithm that, by design, features a female clinician and Black patient.
“We spent 2 years debating the best revascularization strategies and we’re considered experts in the field – but when we talk to our patients, they really don’t know the benefits and risks,” she said. “In order to translate it to the layperson in basic terms, it’s important to say, ‘If you choose this option, you will likely live longer’ rather than using the jargon.”
DAPT, staged PCI, stable IHD
Among the top 10 take-home messages highlighted by the authors is a 2a recommendation that 1-3 months of dual antiplatelet therapy (DAPT) after PCI with a transition to P2Y12 inhibitor monotherapy is “reasonable” in selected patients to reduce the risk of bleeding events. Previous recommendations called for 6 or 12 months of DAPT.
“We really respect all of the clinical trials that came out showing that a shorter duration of DAPT is not inferior in terms of ischemic events but less bleeding, yet I don’t know how many clinicians are actually just using 3 months of DAPT followed by P2Y12 monotherapy,” guideline committee vice chair Jacqueline Tamis-Holland, MD, professor of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an interview. “So while it’s not a big, glaring giant recommendation, I think it will change a lot of practice.”
Similarly, she suggested that practice may shift as a result of a class 1 recommendation for staged PCI of a significantly stenosed nonculprit artery to reduce the risk for death or MI in selected hemodynamically stable patients presenting with ST-segment elevation MI and multivessel disease. “When you survey physicians, 75% of them do staged PCI but I think there will probably be more of an approach to staged PCI, as opposed to doing multivessel PCI at the time of primary PCI.”
Newer evidence from meta-analyses and the landmark ISCHEMIA trial showing no advantage of CABG over medical therapy in stable ischemic heart disease is reflected in a new class 2b recommendation – downgraded from class 1 in 2011 – that CABG “may be reasonable” to improve survival in stable patients with triple-vessel CAD.
The writing committee concluded that the ability of PCI to improve survival, compared with medical therapy in multivessel CAD “remains uncertain.”
Other recommendations likely to be of interest are that the radial artery is preferred, after the left internal mammary artery, as a surgical revascularization conduit over use of a saphenous vein conduit. Benefits include superior patency, fewer adverse cardiac events, and improved survival, the committee noted.
The radial artery is also recommended (class 1) in patients undergoing PCI who have acute coronary syndromes or stable ischemic heart disease to reduce bleeding and vascular complications compared with a femoral approach.
“Having both new radial recommendations sort of makes a bit of tension because the interventionalist is going to want to use the radial artery, but also the surgeon is too,” observed Dr. Tamis-Holland. “We see that in our own practice, so we try to have a collaborative approach to the patient to say: ‘Maybe do the cardiac cath in the dominant radial and then we can use the nondominant radial for a bypass conduit,’ but using both for each revascularization strategy will benefit the patient.
“So, we just have to remember that we’re going to talk together as a heart team and try to make the best decisions for each patient.”
A version of this article first appeared on Medscape.com.
New AKI risk score for PCI patients passes validation
A pair of updated scoring models for estimating a patient’s risk for contrast-associated acute kidney injury during and immediately after percutaneous coronary intervention worked better than a widely used prior version in initial validation testing using data collected at a single U.S. tertiary-care hospital.
While the two new risk scores looked promising, they need further, external validation with additional, diverse patient cohorts, Roxana Mehran, MD, cautioned at the American Heart Association scientific sessions.
“Don’t change anything until we externally validate this,” urged Dr. Mehran, professor and director of the Center for Interventional Cardiovascular Research and Clinical Trials at Icahn School of Medicine at Mount Sinai in New York. External validation of the two new risk scores is in progress with planned reporting of the results in 2022, she said in an interview.
One of the two new algorithms, which both predict a patient’s risk for developing acute kidney injury (AKI) as a result of receiving iodinated contrast media within 48 hours of a percutaneous coronary intervention (PCI), relies on eight easily available variables taken from a patient’s medical record just prior to undergoing PCI: age, type of coronary disease (ranging from asymptomatic or stable angina to ST-segment elevation MI), estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, hemoglobin, basal glucose, and heart failure.
This risk score accounted for 72% (a C-statistic of 0.72) of the observed AKI episodes during the derivation phase, which used data from 14,616 consecutive Mount Sinai patients who underwent PCI during January 2012–December 2017.
Internal validation using data from 5,606 consecutive Mount Sinai patients who underwent PCI during January 2018–December 2020 showed that the eight-item formula accounted for 84% of all incident AKI events occurring during or within 48 hours of a PCI procedure.
Accounting for periprocedural variables
A second risk score included the eight preprocedural variables plus four additional periprocedural variables: complex PCI anatomy, contrast volume during the procedure, development of a periprocedural bleed, and having slow or no reflow into affected coronaries (less than TIMI grade 3 flow) immediately after the procedure. The second model produced a C-statistic of 0.74 during derivation and accounted for 86% of incident AKI events in the validation analysis.
The data Dr. Mehran reported appeared in The Lancet .
She and her coauthors designed these two new algorithms to replace a “widely used” and externally validated risk score that Dr. Mehran and associates introduced in 2004. Despite its merits, the 17-year-old scoring formula has limitations including “low discrimination” with a C-statistic of 0.67, derivation from data that’s now 20 years old, and exclusion of patients with ST-elevation MIs, the authors said in the new report.
Dr. Mehran encouraged interventional cardiologists to use both new risk scores (once externally validated) when possible.
The eight-item preprocedural model “gives clinicians an idea about a patient’s risk [for incident AKI] before they go into the catheterization laboratory,” and then they can further refine the risk assessment during the procedure based on the four periprocedural risk factors, she explained. The goal is to target “tailored preventive strategies” to patients identified by the scoring algorithms as being at high risk for AKI.
A role for preventive measures
Preventive strategies to consider for higher-risk patients include limiting the administered volume of iodinated contrast media, increasing hydration, and avoiding nephrotoxic agents, Dr. Mehran said. The two new risk-assessment tools will “allow for better evaluation of PCI patients” when testing “innovative strategies and treatments” designed to help avoid contrast-associated AKI.
“The focus to date has been on measures to protect renal function from contrast media, based on indirect data,” Estelle C. Nijssen, MSc, and Joachim E. Wildberger, MD, wrote in an editorial that accompanied the published report. “The effect of prophylactic measures on longer-term averse outcomes is still unclear,” they noted. “Perhaps our focus should shift from contrast and renal function to the heart, the role of which has probably been undervalued in this setting,” wrote Ms. Nijssen, a researcher at Maastricht (The Netherlands) University, and Dr. Wildberger, professor and chairman of the department of radiology at Maastricht University.
The editorial’s authors noted that the two new risk scores have the advantage of relying on variables that are “readily available in clinical practice.” But they also noted several limitations, such as the model’s development from largely low-risk patients who had a low, roughly 30% prevalence of chronic kidney disease. During 9 full years studied, 2012-2020, the annual incidence of AKI showed a downward trend, with an incidence of just over 3% in 2020.
Dr. Mehran attributed this decline in AKI to “great work identifying high-risk patients” and using the prophylactic measures she cited. But even when occurring at relatively low incidence, “AKI is still an important complication that is associated with mortality post PCI,” she stressed.
Establishing a safe contrast dose
“The study is great, and helps reinforce the risk factors that are most important to consider when risk stratifying patients prior to PCI,” said Neal Yuan, MD, a cardiologist at the University of California, San Francisco, who has studied contrast-associated AKI in patients who undergo PCI. The report from Dr. Mehran also “confirms in a large cohort the association between contrast-associated AKI and death,” and describes “an easy method for calculating risk,” he said in an interview.
Dr. Yuan agreed on the need for external validation, and once adequately validated he called for incorporation of the risk score into EHRs. Another important issue for future study is “how much [AKI] risk is too much risk,” he said.
The risk factors identified in Dr. Mehran’s report “are some of the same ones identified in previous studies. Even though this was a more contemporary dataset, there is not a ton of new [findings]; it mainly strengthens findings from prior studies.”
Results published by Dr. Yuan and his associates in 2020 used data from more than 20,000 U.S. patients who underwent PCI to try to identify a generally safe upper limit for the dose of iodinated contrast.
The main purpose for performing AKI risk stratification on PCI patients is to “identify high-risk patients and use preventive strategies when treating these patients.” Current AKI preventive strategies “mainly fall into intravascular volume expansion, and reduced contrast.” What’s less clear is “how to operationalize reduced contrast,” he said.
The report by Dr. Yuan showed that “about 10% of PCI patients were at very high risk” for contrast-associated AKI “no matter what is done.” In contrast, about two-thirds of PCI patients “could receive lots of contrast and still be very unlikely to develop AKI,” Dr. Yuan said.
He voiced some skepticism about the willingness of many clinicians to routinely use a formal risk score to assess their patients scheduled for PCI.
Most operators “approximate AKI risk based on variables such as age and creatinine level, but few take time to put the variables into a calculator to get an exact risk number.” In a “small survey” he ran, he found that these rough approximations often ignore important risk factors like hemoglobin level. This inertia by clinicians against routinely using a risk score could be addressed, at least in part, by integrating the risk score into an EHR for automatic calculation, Dr. Yuan suggested.
Dr. Mehran noted that the risk score that she introduced in 2004 is used “in many EHRs to identify high-risk patients.”
The current study received no commercial or external funding. Dr. Mehran has been a consultant to Boston Scientific, Cine-Med Research, CIRM, and Janssen, and she holds equity in Applied Therapeutics, Elixir Medical, and STEL. Dr. Wildberger had no relevant disclosures. Ms. Nijssen and Dr. Yuan had no disclosures.
A pair of updated scoring models for estimating a patient’s risk for contrast-associated acute kidney injury during and immediately after percutaneous coronary intervention worked better than a widely used prior version in initial validation testing using data collected at a single U.S. tertiary-care hospital.
While the two new risk scores looked promising, they need further, external validation with additional, diverse patient cohorts, Roxana Mehran, MD, cautioned at the American Heart Association scientific sessions.
“Don’t change anything until we externally validate this,” urged Dr. Mehran, professor and director of the Center for Interventional Cardiovascular Research and Clinical Trials at Icahn School of Medicine at Mount Sinai in New York. External validation of the two new risk scores is in progress with planned reporting of the results in 2022, she said in an interview.
One of the two new algorithms, which both predict a patient’s risk for developing acute kidney injury (AKI) as a result of receiving iodinated contrast media within 48 hours of a percutaneous coronary intervention (PCI), relies on eight easily available variables taken from a patient’s medical record just prior to undergoing PCI: age, type of coronary disease (ranging from asymptomatic or stable angina to ST-segment elevation MI), estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, hemoglobin, basal glucose, and heart failure.
This risk score accounted for 72% (a C-statistic of 0.72) of the observed AKI episodes during the derivation phase, which used data from 14,616 consecutive Mount Sinai patients who underwent PCI during January 2012–December 2017.
Internal validation using data from 5,606 consecutive Mount Sinai patients who underwent PCI during January 2018–December 2020 showed that the eight-item formula accounted for 84% of all incident AKI events occurring during or within 48 hours of a PCI procedure.
Accounting for periprocedural variables
A second risk score included the eight preprocedural variables plus four additional periprocedural variables: complex PCI anatomy, contrast volume during the procedure, development of a periprocedural bleed, and having slow or no reflow into affected coronaries (less than TIMI grade 3 flow) immediately after the procedure. The second model produced a C-statistic of 0.74 during derivation and accounted for 86% of incident AKI events in the validation analysis.
The data Dr. Mehran reported appeared in The Lancet .
She and her coauthors designed these two new algorithms to replace a “widely used” and externally validated risk score that Dr. Mehran and associates introduced in 2004. Despite its merits, the 17-year-old scoring formula has limitations including “low discrimination” with a C-statistic of 0.67, derivation from data that’s now 20 years old, and exclusion of patients with ST-elevation MIs, the authors said in the new report.
Dr. Mehran encouraged interventional cardiologists to use both new risk scores (once externally validated) when possible.
The eight-item preprocedural model “gives clinicians an idea about a patient’s risk [for incident AKI] before they go into the catheterization laboratory,” and then they can further refine the risk assessment during the procedure based on the four periprocedural risk factors, she explained. The goal is to target “tailored preventive strategies” to patients identified by the scoring algorithms as being at high risk for AKI.
A role for preventive measures
Preventive strategies to consider for higher-risk patients include limiting the administered volume of iodinated contrast media, increasing hydration, and avoiding nephrotoxic agents, Dr. Mehran said. The two new risk-assessment tools will “allow for better evaluation of PCI patients” when testing “innovative strategies and treatments” designed to help avoid contrast-associated AKI.
“The focus to date has been on measures to protect renal function from contrast media, based on indirect data,” Estelle C. Nijssen, MSc, and Joachim E. Wildberger, MD, wrote in an editorial that accompanied the published report. “The effect of prophylactic measures on longer-term averse outcomes is still unclear,” they noted. “Perhaps our focus should shift from contrast and renal function to the heart, the role of which has probably been undervalued in this setting,” wrote Ms. Nijssen, a researcher at Maastricht (The Netherlands) University, and Dr. Wildberger, professor and chairman of the department of radiology at Maastricht University.
The editorial’s authors noted that the two new risk scores have the advantage of relying on variables that are “readily available in clinical practice.” But they also noted several limitations, such as the model’s development from largely low-risk patients who had a low, roughly 30% prevalence of chronic kidney disease. During 9 full years studied, 2012-2020, the annual incidence of AKI showed a downward trend, with an incidence of just over 3% in 2020.
Dr. Mehran attributed this decline in AKI to “great work identifying high-risk patients” and using the prophylactic measures she cited. But even when occurring at relatively low incidence, “AKI is still an important complication that is associated with mortality post PCI,” she stressed.
Establishing a safe contrast dose
“The study is great, and helps reinforce the risk factors that are most important to consider when risk stratifying patients prior to PCI,” said Neal Yuan, MD, a cardiologist at the University of California, San Francisco, who has studied contrast-associated AKI in patients who undergo PCI. The report from Dr. Mehran also “confirms in a large cohort the association between contrast-associated AKI and death,” and describes “an easy method for calculating risk,” he said in an interview.
Dr. Yuan agreed on the need for external validation, and once adequately validated he called for incorporation of the risk score into EHRs. Another important issue for future study is “how much [AKI] risk is too much risk,” he said.
The risk factors identified in Dr. Mehran’s report “are some of the same ones identified in previous studies. Even though this was a more contemporary dataset, there is not a ton of new [findings]; it mainly strengthens findings from prior studies.”
Results published by Dr. Yuan and his associates in 2020 used data from more than 20,000 U.S. patients who underwent PCI to try to identify a generally safe upper limit for the dose of iodinated contrast.
The main purpose for performing AKI risk stratification on PCI patients is to “identify high-risk patients and use preventive strategies when treating these patients.” Current AKI preventive strategies “mainly fall into intravascular volume expansion, and reduced contrast.” What’s less clear is “how to operationalize reduced contrast,” he said.
The report by Dr. Yuan showed that “about 10% of PCI patients were at very high risk” for contrast-associated AKI “no matter what is done.” In contrast, about two-thirds of PCI patients “could receive lots of contrast and still be very unlikely to develop AKI,” Dr. Yuan said.
He voiced some skepticism about the willingness of many clinicians to routinely use a formal risk score to assess their patients scheduled for PCI.
Most operators “approximate AKI risk based on variables such as age and creatinine level, but few take time to put the variables into a calculator to get an exact risk number.” In a “small survey” he ran, he found that these rough approximations often ignore important risk factors like hemoglobin level. This inertia by clinicians against routinely using a risk score could be addressed, at least in part, by integrating the risk score into an EHR for automatic calculation, Dr. Yuan suggested.
Dr. Mehran noted that the risk score that she introduced in 2004 is used “in many EHRs to identify high-risk patients.”
The current study received no commercial or external funding. Dr. Mehran has been a consultant to Boston Scientific, Cine-Med Research, CIRM, and Janssen, and she holds equity in Applied Therapeutics, Elixir Medical, and STEL. Dr. Wildberger had no relevant disclosures. Ms. Nijssen and Dr. Yuan had no disclosures.
A pair of updated scoring models for estimating a patient’s risk for contrast-associated acute kidney injury during and immediately after percutaneous coronary intervention worked better than a widely used prior version in initial validation testing using data collected at a single U.S. tertiary-care hospital.
While the two new risk scores looked promising, they need further, external validation with additional, diverse patient cohorts, Roxana Mehran, MD, cautioned at the American Heart Association scientific sessions.
“Don’t change anything until we externally validate this,” urged Dr. Mehran, professor and director of the Center for Interventional Cardiovascular Research and Clinical Trials at Icahn School of Medicine at Mount Sinai in New York. External validation of the two new risk scores is in progress with planned reporting of the results in 2022, she said in an interview.
One of the two new algorithms, which both predict a patient’s risk for developing acute kidney injury (AKI) as a result of receiving iodinated contrast media within 48 hours of a percutaneous coronary intervention (PCI), relies on eight easily available variables taken from a patient’s medical record just prior to undergoing PCI: age, type of coronary disease (ranging from asymptomatic or stable angina to ST-segment elevation MI), estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, hemoglobin, basal glucose, and heart failure.
This risk score accounted for 72% (a C-statistic of 0.72) of the observed AKI episodes during the derivation phase, which used data from 14,616 consecutive Mount Sinai patients who underwent PCI during January 2012–December 2017.
Internal validation using data from 5,606 consecutive Mount Sinai patients who underwent PCI during January 2018–December 2020 showed that the eight-item formula accounted for 84% of all incident AKI events occurring during or within 48 hours of a PCI procedure.
Accounting for periprocedural variables
A second risk score included the eight preprocedural variables plus four additional periprocedural variables: complex PCI anatomy, contrast volume during the procedure, development of a periprocedural bleed, and having slow or no reflow into affected coronaries (less than TIMI grade 3 flow) immediately after the procedure. The second model produced a C-statistic of 0.74 during derivation and accounted for 86% of incident AKI events in the validation analysis.
The data Dr. Mehran reported appeared in The Lancet .
She and her coauthors designed these two new algorithms to replace a “widely used” and externally validated risk score that Dr. Mehran and associates introduced in 2004. Despite its merits, the 17-year-old scoring formula has limitations including “low discrimination” with a C-statistic of 0.67, derivation from data that’s now 20 years old, and exclusion of patients with ST-elevation MIs, the authors said in the new report.
Dr. Mehran encouraged interventional cardiologists to use both new risk scores (once externally validated) when possible.
The eight-item preprocedural model “gives clinicians an idea about a patient’s risk [for incident AKI] before they go into the catheterization laboratory,” and then they can further refine the risk assessment during the procedure based on the four periprocedural risk factors, she explained. The goal is to target “tailored preventive strategies” to patients identified by the scoring algorithms as being at high risk for AKI.
A role for preventive measures
Preventive strategies to consider for higher-risk patients include limiting the administered volume of iodinated contrast media, increasing hydration, and avoiding nephrotoxic agents, Dr. Mehran said. The two new risk-assessment tools will “allow for better evaluation of PCI patients” when testing “innovative strategies and treatments” designed to help avoid contrast-associated AKI.
“The focus to date has been on measures to protect renal function from contrast media, based on indirect data,” Estelle C. Nijssen, MSc, and Joachim E. Wildberger, MD, wrote in an editorial that accompanied the published report. “The effect of prophylactic measures on longer-term averse outcomes is still unclear,” they noted. “Perhaps our focus should shift from contrast and renal function to the heart, the role of which has probably been undervalued in this setting,” wrote Ms. Nijssen, a researcher at Maastricht (The Netherlands) University, and Dr. Wildberger, professor and chairman of the department of radiology at Maastricht University.
The editorial’s authors noted that the two new risk scores have the advantage of relying on variables that are “readily available in clinical practice.” But they also noted several limitations, such as the model’s development from largely low-risk patients who had a low, roughly 30% prevalence of chronic kidney disease. During 9 full years studied, 2012-2020, the annual incidence of AKI showed a downward trend, with an incidence of just over 3% in 2020.
Dr. Mehran attributed this decline in AKI to “great work identifying high-risk patients” and using the prophylactic measures she cited. But even when occurring at relatively low incidence, “AKI is still an important complication that is associated with mortality post PCI,” she stressed.
Establishing a safe contrast dose
“The study is great, and helps reinforce the risk factors that are most important to consider when risk stratifying patients prior to PCI,” said Neal Yuan, MD, a cardiologist at the University of California, San Francisco, who has studied contrast-associated AKI in patients who undergo PCI. The report from Dr. Mehran also “confirms in a large cohort the association between contrast-associated AKI and death,” and describes “an easy method for calculating risk,” he said in an interview.
Dr. Yuan agreed on the need for external validation, and once adequately validated he called for incorporation of the risk score into EHRs. Another important issue for future study is “how much [AKI] risk is too much risk,” he said.
The risk factors identified in Dr. Mehran’s report “are some of the same ones identified in previous studies. Even though this was a more contemporary dataset, there is not a ton of new [findings]; it mainly strengthens findings from prior studies.”
Results published by Dr. Yuan and his associates in 2020 used data from more than 20,000 U.S. patients who underwent PCI to try to identify a generally safe upper limit for the dose of iodinated contrast.
The main purpose for performing AKI risk stratification on PCI patients is to “identify high-risk patients and use preventive strategies when treating these patients.” Current AKI preventive strategies “mainly fall into intravascular volume expansion, and reduced contrast.” What’s less clear is “how to operationalize reduced contrast,” he said.
The report by Dr. Yuan showed that “about 10% of PCI patients were at very high risk” for contrast-associated AKI “no matter what is done.” In contrast, about two-thirds of PCI patients “could receive lots of contrast and still be very unlikely to develop AKI,” Dr. Yuan said.
He voiced some skepticism about the willingness of many clinicians to routinely use a formal risk score to assess their patients scheduled for PCI.
Most operators “approximate AKI risk based on variables such as age and creatinine level, but few take time to put the variables into a calculator to get an exact risk number.” In a “small survey” he ran, he found that these rough approximations often ignore important risk factors like hemoglobin level. This inertia by clinicians against routinely using a risk score could be addressed, at least in part, by integrating the risk score into an EHR for automatic calculation, Dr. Yuan suggested.
Dr. Mehran noted that the risk score that she introduced in 2004 is used “in many EHRs to identify high-risk patients.”
The current study received no commercial or external funding. Dr. Mehran has been a consultant to Boston Scientific, Cine-Med Research, CIRM, and Janssen, and she holds equity in Applied Therapeutics, Elixir Medical, and STEL. Dr. Wildberger had no relevant disclosures. Ms. Nijssen and Dr. Yuan had no disclosures.
FROM AHA 2021
FDA flags cardiac perforation risks during leadless pacemaker implantation
The Food and Drug Administration is reminding health care providers about the risk of major complications if cardiac perforation occurs during leadless pacemaker implantation.
Cardiac perforation is a rare complication and the overall risk associated with leadless pacemaker implantation appears similar to that with traditional transvenous pacemakers, the agency says. However, premarket clinical studies of the Micra leadless pacemaker (Medtronic) suggested major complications related to cardiac perforation appear to be more severe for those receiving a leadless pacemaker.
“Information from real-world use suggests that cardiac perforations associated with Micra leadless pacemakers are more likely to be associated with serious complications, such as cardiac tamponade or death, than with traditional pacemakers,” the FDA said Nov. 17 in a letter to health care professionals.
“The FDA is bringing this information to your attention as a reminder and to encourage you to report leadless pacemaker cardiac perforations and complications related to perforation to the manufacturer and the FDA,” it notes.
The Micra Transcatheter Pacing System in 2015 was the first leadless pacemaker approved in Europe, and was approved in the United States the following year with a mandated postapproval study to help assess continued safety and efficacy. The Micra device is currently the only approved leadless pacemaker in the United States.
The FDA continues to evaluate outcomes in patients who receive leadless pacing systems and recommends that health care providers discuss the risks and benefits of available pacing system options with patients as part of shared clinical decision-making.
Providers are advised to read and carefully follow the instructions for use and training for Medtronic’s Micra pacemaker.
Any adverse events or suspected adverse events related to the Micra Transcatheter Pacing System or any other pacemaker systems should be reported to the FDA through MedWatch, its adverse-event reporting program.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is reminding health care providers about the risk of major complications if cardiac perforation occurs during leadless pacemaker implantation.
Cardiac perforation is a rare complication and the overall risk associated with leadless pacemaker implantation appears similar to that with traditional transvenous pacemakers, the agency says. However, premarket clinical studies of the Micra leadless pacemaker (Medtronic) suggested major complications related to cardiac perforation appear to be more severe for those receiving a leadless pacemaker.
“Information from real-world use suggests that cardiac perforations associated with Micra leadless pacemakers are more likely to be associated with serious complications, such as cardiac tamponade or death, than with traditional pacemakers,” the FDA said Nov. 17 in a letter to health care professionals.
“The FDA is bringing this information to your attention as a reminder and to encourage you to report leadless pacemaker cardiac perforations and complications related to perforation to the manufacturer and the FDA,” it notes.
The Micra Transcatheter Pacing System in 2015 was the first leadless pacemaker approved in Europe, and was approved in the United States the following year with a mandated postapproval study to help assess continued safety and efficacy. The Micra device is currently the only approved leadless pacemaker in the United States.
The FDA continues to evaluate outcomes in patients who receive leadless pacing systems and recommends that health care providers discuss the risks and benefits of available pacing system options with patients as part of shared clinical decision-making.
Providers are advised to read and carefully follow the instructions for use and training for Medtronic’s Micra pacemaker.
Any adverse events or suspected adverse events related to the Micra Transcatheter Pacing System or any other pacemaker systems should be reported to the FDA through MedWatch, its adverse-event reporting program.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is reminding health care providers about the risk of major complications if cardiac perforation occurs during leadless pacemaker implantation.
Cardiac perforation is a rare complication and the overall risk associated with leadless pacemaker implantation appears similar to that with traditional transvenous pacemakers, the agency says. However, premarket clinical studies of the Micra leadless pacemaker (Medtronic) suggested major complications related to cardiac perforation appear to be more severe for those receiving a leadless pacemaker.
“Information from real-world use suggests that cardiac perforations associated with Micra leadless pacemakers are more likely to be associated with serious complications, such as cardiac tamponade or death, than with traditional pacemakers,” the FDA said Nov. 17 in a letter to health care professionals.
“The FDA is bringing this information to your attention as a reminder and to encourage you to report leadless pacemaker cardiac perforations and complications related to perforation to the manufacturer and the FDA,” it notes.
The Micra Transcatheter Pacing System in 2015 was the first leadless pacemaker approved in Europe, and was approved in the United States the following year with a mandated postapproval study to help assess continued safety and efficacy. The Micra device is currently the only approved leadless pacemaker in the United States.
The FDA continues to evaluate outcomes in patients who receive leadless pacing systems and recommends that health care providers discuss the risks and benefits of available pacing system options with patients as part of shared clinical decision-making.
Providers are advised to read and carefully follow the instructions for use and training for Medtronic’s Micra pacemaker.
Any adverse events or suspected adverse events related to the Micra Transcatheter Pacing System or any other pacemaker systems should be reported to the FDA through MedWatch, its adverse-event reporting program.
A version of this article first appeared on Medscape.com.
Exercise reduces arm and shoulder problems after breast cancer surgery
However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.
“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.
Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.
“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.
In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.
At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.
“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”
While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.
“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.
The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.
However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.
“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.
Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.
“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.
In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.
At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.
“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”
While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.
“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.
The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.
However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.
“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.
Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.
“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.
In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.
At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.
“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”
While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.
“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.
The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.
FROM THE BMJ
PRAGUE-17: LAA closure holds up against DOACs out to 4 years
Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.
At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).
The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).
Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.
The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.
The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).
The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.
Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.
During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.
Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”
He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.
In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.
“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.
NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”
Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.
“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.
The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.
“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”
The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.
At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).
The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).
Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.
The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.
The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).
The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.
Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.
During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.
Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”
He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.
In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.
“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.
NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”
Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.
“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.
The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.
“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”
The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.
At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).
The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).
Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.
The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.
The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).
The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.
Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.
During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.
Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”
He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.
In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.
“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.
NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”
Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.
“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.
The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.
“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”
The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM TCT 2021
No advantage shown for LAA ligation as adjunct to pulmonary vein isolation
In patients treated for persistent atrial fibrillation (AFib) with pulmonary vein antral isolation (PVAI), there was a numerical but not a statistical advantage for adjunctive left atrial appendage (LAA) ligation in a multicenter randomized trial.
The study, called aMAZE, was conducted with the LARIAT LAA (AtriCure) ligation system. AtriCure announced in August that the primary efficacy endpoint was not met; the full results were presented Nov. 14 at the American Heart Association scientific sessions.
Exploratory analyses suggested that some subgroups might benefit, but the overall 4.3% advantage provided by adjunctive LAA ligation for freedom from atrial arrhythmias (AA) at 12 months “did not meet predefined criteria for superiority,” according to coprincipal investigator David J. Wilber, MD.
Based on evidence that the LAA contributes substrate for generation of persistent AFib, the hypothesis of the study was that LAA ligation would improve on long-term rhythm control achieved with PVAI alone, which Dr. Wilber noted is currently suboptimal. The LARIAT device is deployed percutaneously into the LAA sac, where it seals off the opening to the left atrium, potentially blocking a pathway for rhythm disturbances.
The study randomized 610 patients at 53 sites in the United States in a 2:1 ratio to LARIAT LAA ligation plus PVAI or to PVAI alone. Enrollment criteria included longstanding persistent and symptomatic AFib and prior failure of ablation therapy. AA was defined as freedom from more than 30 seconds of AFib, atrial flutter, or atrial tachycardia 12 months after treatment without new or increased dosages of antiarrhythmia therapy.
The primary safety endpoint was a composite of serious adverse events within 30 days of placement of the LARIAT device. Technical success was defined as ≤1 mm (+/– 1 mm) residual communication between the LAA and the left atrium.
At 12 months, AA was achieved in 59.9% of those treated with PVAI alone and 64.3% in those who received the LARIAT ligation procedure in addition to PVAI. The P value for superiority was not significant (P = .835).
At 3.4%, the incidence of serious events at 30 days was considered reasonable, leading Dr. Wilber, director of electrophysiology at Loyola University in Chicago, to conclude that the LARIAT system “appears safe.” Overall, bleeding events requiring intervention occurred in 2.2%, cardiac structural injuries requiring surgery occurred in 0.8%, and vascular injuries requiring surgery occurred in 0.3%.
Technical success at 30 days was achieved by the study definition in 81%. If defined as a residual communication of 5 mm or less, the technical success rate was 99%.
Two groups appeared to potentially benefit in exploratory analyses. When stratified by AFib duration, there was a relative 7.5% reduction in AA for those who received LARIAT plus PVAI relative to PVAI alone. This trended towards statistical significance (P = .084), but no advantage was seen for those with longer duration of AFib.
For those with a median volume of at least133 cm3, the advantage of LARIAT for the primary endpoint was 12.4%. This also trended toward significance (P = .093). Conversely, there was a numerical disadvantage for LARIAT plus PVAI relative to PVAI alone for AA at 12 months.
While Dr. Wilber stressed that these analyses were not prespecified and require further exploration, he did conclude that strategies to build on the current success of PVAI with adjunctive strategies “may require some individualization,” taking into account patient or disease characteristics that exert an impact on risk of recurrent AA.
As an AHA-invited discussant on this trial, Usha B. Tedrow, MD, director of the clinical cardiac electrophysiology fellowship at Brigham and Women’s Hospital, Boston, reiterated that this study failed to meet its primary endpoint, but she agreed with the premise that “some subgroups may benefit.”
She identified several aspects of AFib pathophysiology involving the pulmonary vein and the LAA as well as prior studies that suggest the LAA might be a target for adjunctive therapy in patients treated with PVAI for persistent AFib. On this basis, she suggested that there might be other directions to explore before ruling out a role of the LARIAT device in all patients. For example, PVAI plus LARIAT ligation plus another adjunctive ablation intervention might be considered to add durable rhythm control.
She also said that the rigorous conduct of the aMAZE trial might have been a relative obstacle to its own success. Although she praised the meticulous design and conduct of the trial, it might have resulted in an uncommon benefit in controls that diluted the results.
“The success rate in the PVAI group in aMAZE was higher than standard ablation in previous studies looking at LAA exclusion. Could the strict protocol have played a role?” she asked.
Dr. Wilbur reports financial relationships with Abbott, Biosense Webster, Boston Scientific, and AtriCure, which provided funding for this study. Dr. Tedrow reports financial relationships with Abbott, Baylis Medical, Boston Scientific, Biosense Webster, and Thermedical.
In patients treated for persistent atrial fibrillation (AFib) with pulmonary vein antral isolation (PVAI), there was a numerical but not a statistical advantage for adjunctive left atrial appendage (LAA) ligation in a multicenter randomized trial.
The study, called aMAZE, was conducted with the LARIAT LAA (AtriCure) ligation system. AtriCure announced in August that the primary efficacy endpoint was not met; the full results were presented Nov. 14 at the American Heart Association scientific sessions.
Exploratory analyses suggested that some subgroups might benefit, but the overall 4.3% advantage provided by adjunctive LAA ligation for freedom from atrial arrhythmias (AA) at 12 months “did not meet predefined criteria for superiority,” according to coprincipal investigator David J. Wilber, MD.
Based on evidence that the LAA contributes substrate for generation of persistent AFib, the hypothesis of the study was that LAA ligation would improve on long-term rhythm control achieved with PVAI alone, which Dr. Wilber noted is currently suboptimal. The LARIAT device is deployed percutaneously into the LAA sac, where it seals off the opening to the left atrium, potentially blocking a pathway for rhythm disturbances.
The study randomized 610 patients at 53 sites in the United States in a 2:1 ratio to LARIAT LAA ligation plus PVAI or to PVAI alone. Enrollment criteria included longstanding persistent and symptomatic AFib and prior failure of ablation therapy. AA was defined as freedom from more than 30 seconds of AFib, atrial flutter, or atrial tachycardia 12 months after treatment without new or increased dosages of antiarrhythmia therapy.
The primary safety endpoint was a composite of serious adverse events within 30 days of placement of the LARIAT device. Technical success was defined as ≤1 mm (+/– 1 mm) residual communication between the LAA and the left atrium.
At 12 months, AA was achieved in 59.9% of those treated with PVAI alone and 64.3% in those who received the LARIAT ligation procedure in addition to PVAI. The P value for superiority was not significant (P = .835).
At 3.4%, the incidence of serious events at 30 days was considered reasonable, leading Dr. Wilber, director of electrophysiology at Loyola University in Chicago, to conclude that the LARIAT system “appears safe.” Overall, bleeding events requiring intervention occurred in 2.2%, cardiac structural injuries requiring surgery occurred in 0.8%, and vascular injuries requiring surgery occurred in 0.3%.
Technical success at 30 days was achieved by the study definition in 81%. If defined as a residual communication of 5 mm or less, the technical success rate was 99%.
Two groups appeared to potentially benefit in exploratory analyses. When stratified by AFib duration, there was a relative 7.5% reduction in AA for those who received LARIAT plus PVAI relative to PVAI alone. This trended towards statistical significance (P = .084), but no advantage was seen for those with longer duration of AFib.
For those with a median volume of at least133 cm3, the advantage of LARIAT for the primary endpoint was 12.4%. This also trended toward significance (P = .093). Conversely, there was a numerical disadvantage for LARIAT plus PVAI relative to PVAI alone for AA at 12 months.
While Dr. Wilber stressed that these analyses were not prespecified and require further exploration, he did conclude that strategies to build on the current success of PVAI with adjunctive strategies “may require some individualization,” taking into account patient or disease characteristics that exert an impact on risk of recurrent AA.
As an AHA-invited discussant on this trial, Usha B. Tedrow, MD, director of the clinical cardiac electrophysiology fellowship at Brigham and Women’s Hospital, Boston, reiterated that this study failed to meet its primary endpoint, but she agreed with the premise that “some subgroups may benefit.”
She identified several aspects of AFib pathophysiology involving the pulmonary vein and the LAA as well as prior studies that suggest the LAA might be a target for adjunctive therapy in patients treated with PVAI for persistent AFib. On this basis, she suggested that there might be other directions to explore before ruling out a role of the LARIAT device in all patients. For example, PVAI plus LARIAT ligation plus another adjunctive ablation intervention might be considered to add durable rhythm control.
She also said that the rigorous conduct of the aMAZE trial might have been a relative obstacle to its own success. Although she praised the meticulous design and conduct of the trial, it might have resulted in an uncommon benefit in controls that diluted the results.
“The success rate in the PVAI group in aMAZE was higher than standard ablation in previous studies looking at LAA exclusion. Could the strict protocol have played a role?” she asked.
Dr. Wilbur reports financial relationships with Abbott, Biosense Webster, Boston Scientific, and AtriCure, which provided funding for this study. Dr. Tedrow reports financial relationships with Abbott, Baylis Medical, Boston Scientific, Biosense Webster, and Thermedical.
In patients treated for persistent atrial fibrillation (AFib) with pulmonary vein antral isolation (PVAI), there was a numerical but not a statistical advantage for adjunctive left atrial appendage (LAA) ligation in a multicenter randomized trial.
The study, called aMAZE, was conducted with the LARIAT LAA (AtriCure) ligation system. AtriCure announced in August that the primary efficacy endpoint was not met; the full results were presented Nov. 14 at the American Heart Association scientific sessions.
Exploratory analyses suggested that some subgroups might benefit, but the overall 4.3% advantage provided by adjunctive LAA ligation for freedom from atrial arrhythmias (AA) at 12 months “did not meet predefined criteria for superiority,” according to coprincipal investigator David J. Wilber, MD.
Based on evidence that the LAA contributes substrate for generation of persistent AFib, the hypothesis of the study was that LAA ligation would improve on long-term rhythm control achieved with PVAI alone, which Dr. Wilber noted is currently suboptimal. The LARIAT device is deployed percutaneously into the LAA sac, where it seals off the opening to the left atrium, potentially blocking a pathway for rhythm disturbances.
The study randomized 610 patients at 53 sites in the United States in a 2:1 ratio to LARIAT LAA ligation plus PVAI or to PVAI alone. Enrollment criteria included longstanding persistent and symptomatic AFib and prior failure of ablation therapy. AA was defined as freedom from more than 30 seconds of AFib, atrial flutter, or atrial tachycardia 12 months after treatment without new or increased dosages of antiarrhythmia therapy.
The primary safety endpoint was a composite of serious adverse events within 30 days of placement of the LARIAT device. Technical success was defined as ≤1 mm (+/– 1 mm) residual communication between the LAA and the left atrium.
At 12 months, AA was achieved in 59.9% of those treated with PVAI alone and 64.3% in those who received the LARIAT ligation procedure in addition to PVAI. The P value for superiority was not significant (P = .835).
At 3.4%, the incidence of serious events at 30 days was considered reasonable, leading Dr. Wilber, director of electrophysiology at Loyola University in Chicago, to conclude that the LARIAT system “appears safe.” Overall, bleeding events requiring intervention occurred in 2.2%, cardiac structural injuries requiring surgery occurred in 0.8%, and vascular injuries requiring surgery occurred in 0.3%.
Technical success at 30 days was achieved by the study definition in 81%. If defined as a residual communication of 5 mm or less, the technical success rate was 99%.
Two groups appeared to potentially benefit in exploratory analyses. When stratified by AFib duration, there was a relative 7.5% reduction in AA for those who received LARIAT plus PVAI relative to PVAI alone. This trended towards statistical significance (P = .084), but no advantage was seen for those with longer duration of AFib.
For those with a median volume of at least133 cm3, the advantage of LARIAT for the primary endpoint was 12.4%. This also trended toward significance (P = .093). Conversely, there was a numerical disadvantage for LARIAT plus PVAI relative to PVAI alone for AA at 12 months.
While Dr. Wilber stressed that these analyses were not prespecified and require further exploration, he did conclude that strategies to build on the current success of PVAI with adjunctive strategies “may require some individualization,” taking into account patient or disease characteristics that exert an impact on risk of recurrent AA.
As an AHA-invited discussant on this trial, Usha B. Tedrow, MD, director of the clinical cardiac electrophysiology fellowship at Brigham and Women’s Hospital, Boston, reiterated that this study failed to meet its primary endpoint, but she agreed with the premise that “some subgroups may benefit.”
She identified several aspects of AFib pathophysiology involving the pulmonary vein and the LAA as well as prior studies that suggest the LAA might be a target for adjunctive therapy in patients treated with PVAI for persistent AFib. On this basis, she suggested that there might be other directions to explore before ruling out a role of the LARIAT device in all patients. For example, PVAI plus LARIAT ligation plus another adjunctive ablation intervention might be considered to add durable rhythm control.
She also said that the rigorous conduct of the aMAZE trial might have been a relative obstacle to its own success. Although she praised the meticulous design and conduct of the trial, it might have resulted in an uncommon benefit in controls that diluted the results.
“The success rate in the PVAI group in aMAZE was higher than standard ablation in previous studies looking at LAA exclusion. Could the strict protocol have played a role?” she asked.
Dr. Wilbur reports financial relationships with Abbott, Biosense Webster, Boston Scientific, and AtriCure, which provided funding for this study. Dr. Tedrow reports financial relationships with Abbott, Baylis Medical, Boston Scientific, Biosense Webster, and Thermedical.
FROM AHA 2021
Early SAVR tops watchful waiting in severe, asymptomatic aortic stenosis: AVATAR
Better to intervene early with a new valve in patients with severe aortic stenosis (AS) who are asymptomatic, even during exercise, than to wait for the disease to progress and symptoms to emerge before operating, suggests a small, randomized trial that challenges the guidelines.
Of the trial’s 157 patients, all with negative results on stress tests and normal left ventricular (LV) function despite severe AS, those assigned to early surgical aortic valve replacement (SAVR), compared with standard watchful waiting, showed a better-than-50% drop in risk for death or major adverse cardiac events (MACE) over 2-3 years. The benefit appeared driven by fewer hospitalizations for heart failure (HF) and deaths in the early-surgery group.
The findings “advocate for early surgery once aortic stenosis becomes significant and regardless of symptom status,” Marko Banovic, MD, PhD, said during his presentation at the American Heart Association scientific sessions.
Dr. Banovic, from the University of Belgrade Medical School in Serbia, is coprincipal investigator on the trial, called AVATAR (Aortic Valve Replacement vs. Conservative Treatment in Asymptomatic Severe Aortic Stenosis). He is also lead author on the study’s publication in Circulation, timed to coincide with his AHA presentation.
“The AVATAR findings provide additional evidence to help clinicians in guiding their decision when seeing a patient with significant aortic stenosis, normal left ventricular function, overall low surgical risk, and without significant comorbidities,” Dr. Banovic told this news organization.
European and North American Guidelines favor watchful waiting for asymptomatic patients with severe aortic stenosis, with surgery upon development of symptoms or LV dysfunction, observed Victoria Delgado, MD, PhD, Leiden (the Netherlands) University Medical Center, an invited discussant for the AVATAR presentation.
AVATAR does suggest that “early surgery in truly asymptomatic patients with severe aortic stenosis and preserved ejection fraction seems to provide better outcomes as compared to the conservative treatment,” she said. “But I think that the long-term follow-up for potential events, such as valve durability or endocarditis, is still needed.”
The trial has strengths, compared with the recent RECOVERY trial, which also concluded in favor of early SAVR over watchful waiting in patients described as asymptomatic with severe aortic stenosis. Dr. Delgado and other observers, however, have pointed out limitations of that trial, including questions about whether the patients were truly asymptomatic – stress testing wasn›t routinely performed.
In AVATAR, all patients were negative at stress testing, which required them to reach their estimated maximum heart rate, Dr. Banovic noted. As he and his colleagues write, the trial expands on RECOVERY “by providing evidence of the benefit of early surgery in a setting representative of a dilemma in decision making, in truly asymptomatic patients with severe but not critical aortic stenosis and normal LV function.”
A role for TAVR?
Guidelines in general “can be very conservative and lag behind evidence a bit,” Patricia A. Pellikka, MD, Mayo Clinic, Rochester, Minn., who is not associated with AVATAR, said in an interview.
“I think when we see patients clinically, we can advise them that if they don’t have symptoms and they do have severe aortic stenosis,” she said, “they’re likely going to get symptoms within a reasonably short period of time, according to our retrospective databases, and that doing the intervention early may yield better long-term outcomes.”
The results of AVATAR, in which valve replacement consisted only of SAVR, “probably could be extrapolated” to transcatheter aortic valve replacement (TAVR), Dr. Pellikka observed. “Certainly, TAVR is the procedure that patients come asking for. It’s attractive to avoid a major surgery, and it seems very plausible that TAVR would have yielded similar results if that had been a therapy in this trial.”
In practice, patient age and functional status would figure heavily in deciding whether early valve replacement, and which procedure, is appropriate, Dr. Banovic said in an interview. Importantly, the trial’s patients were at low surgical risk and free of major chronic diseases or other important health concerns.
“Frailty and older age are known risk factors for suboptimal recovery” after SAVR, Dr. Banovic said when interviewed. Therefore, frail patients, who were not many in AVATAR, might be “more suitable for TAVR than SAVR, based on the TAVR-vs.-SAVR results in symptomatic AS patients,” he said.
“One might extrapolate experience from AVATAR trial to TAVR, which may lower the bar for TAVR indications,” but that would require more supporting evidence, Dr. Banovic said.
Confirmed asymptomatic
AVATAR, conducted at nine centers in seven countries in the European Union, randomly assigned 157 adults with severe AS by echocardiography and a LV ejection fraction (LVEF) greater than 50% to early SAVR or conservative management. They averaged 67 years in age, and 43% were women.
The trial excluded anyone with dyspnea, syncope, presyncope, angina, or LV dysfunction and anyone with a history of atrial fibrillation or significant cardiac, renal, or lung disease. The cohort’s average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 1.7%.
The 78 patients in the early-surgery group “were expected” to have the procedure within 8 weeks of randomization, the published report states; the median time was 55 days. Six of them ultimately did not have the surgery. There was only one periprocedural death, for an operative mortality of 1.4%.
The 79 patients assigned to conservative care were later referred for surgery if they developed symptoms, their LVEF dropped below 50%, or they showed a 0.3-m/sec jump in peak aortic jet velocity at follow-up echocardiography. That occurred with 25 patients a median of 400 days after randomization.
The rate of the primary endpoint – death from any cause, acute myocardial infarction, stroke, or unplanned HF hospitalization – was 16.6% in the early-surgery group and 32.9% for those managed conservatively over a median of 32 months. The hazard ratio by intention-to-treat analysis was 0.46 (95% confidence interval, 0.23-0.90; P = .02). The HR for death from any cause or HF hospitalization was 0.40 (95% CI, 0.19-0.84; P = .013). Any differences in the individual endpoints of death, first HF hospitalizations, thromboembolic complications, or major bleeding were not significant.
If early aortic valve replacement is better for patients like those in AVATAR, some sort of screening for previously unknown severe aortic stenosis may seem attractive for selected populations. “Echocardiography would be the screening test for aortic stenosis, but it’s fairly expensive and therefore has never been advocated as a test to screen everyone,” Dr. Pellikka observed.
“But things are changing,” given innovations such as point-of-care ultrasonography and machine learning, she noted. “Artificial intelligence is progressing in its application to echocardiography, and it’s conceivable that in the future, there might be some abbreviated or screening type of test. But I don’t think we’re quite there yet.”
Dr. Banovic had no conflicts; disclosures for the other authors are in the report. Dr. Delgado disclosed speaker fees from Edwards Lifesciences, Abbott Vascular, Medtronic, Merck, Novartis, and GE Healthcare and unrestricted research grants to her institution from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. Dr. Pellikka disclosed receiving a research grant from Ultromics and having unspecified modest relationships with GE Healthcare, Lantheus, and OxThera.
A version of this article first appeared on Medscape.com.
Better to intervene early with a new valve in patients with severe aortic stenosis (AS) who are asymptomatic, even during exercise, than to wait for the disease to progress and symptoms to emerge before operating, suggests a small, randomized trial that challenges the guidelines.
Of the trial’s 157 patients, all with negative results on stress tests and normal left ventricular (LV) function despite severe AS, those assigned to early surgical aortic valve replacement (SAVR), compared with standard watchful waiting, showed a better-than-50% drop in risk for death or major adverse cardiac events (MACE) over 2-3 years. The benefit appeared driven by fewer hospitalizations for heart failure (HF) and deaths in the early-surgery group.
The findings “advocate for early surgery once aortic stenosis becomes significant and regardless of symptom status,” Marko Banovic, MD, PhD, said during his presentation at the American Heart Association scientific sessions.
Dr. Banovic, from the University of Belgrade Medical School in Serbia, is coprincipal investigator on the trial, called AVATAR (Aortic Valve Replacement vs. Conservative Treatment in Asymptomatic Severe Aortic Stenosis). He is also lead author on the study’s publication in Circulation, timed to coincide with his AHA presentation.
“The AVATAR findings provide additional evidence to help clinicians in guiding their decision when seeing a patient with significant aortic stenosis, normal left ventricular function, overall low surgical risk, and without significant comorbidities,” Dr. Banovic told this news organization.
European and North American Guidelines favor watchful waiting for asymptomatic patients with severe aortic stenosis, with surgery upon development of symptoms or LV dysfunction, observed Victoria Delgado, MD, PhD, Leiden (the Netherlands) University Medical Center, an invited discussant for the AVATAR presentation.
AVATAR does suggest that “early surgery in truly asymptomatic patients with severe aortic stenosis and preserved ejection fraction seems to provide better outcomes as compared to the conservative treatment,” she said. “But I think that the long-term follow-up for potential events, such as valve durability or endocarditis, is still needed.”
The trial has strengths, compared with the recent RECOVERY trial, which also concluded in favor of early SAVR over watchful waiting in patients described as asymptomatic with severe aortic stenosis. Dr. Delgado and other observers, however, have pointed out limitations of that trial, including questions about whether the patients were truly asymptomatic – stress testing wasn›t routinely performed.
In AVATAR, all patients were negative at stress testing, which required them to reach their estimated maximum heart rate, Dr. Banovic noted. As he and his colleagues write, the trial expands on RECOVERY “by providing evidence of the benefit of early surgery in a setting representative of a dilemma in decision making, in truly asymptomatic patients with severe but not critical aortic stenosis and normal LV function.”
A role for TAVR?
Guidelines in general “can be very conservative and lag behind evidence a bit,” Patricia A. Pellikka, MD, Mayo Clinic, Rochester, Minn., who is not associated with AVATAR, said in an interview.
“I think when we see patients clinically, we can advise them that if they don’t have symptoms and they do have severe aortic stenosis,” she said, “they’re likely going to get symptoms within a reasonably short period of time, according to our retrospective databases, and that doing the intervention early may yield better long-term outcomes.”
The results of AVATAR, in which valve replacement consisted only of SAVR, “probably could be extrapolated” to transcatheter aortic valve replacement (TAVR), Dr. Pellikka observed. “Certainly, TAVR is the procedure that patients come asking for. It’s attractive to avoid a major surgery, and it seems very plausible that TAVR would have yielded similar results if that had been a therapy in this trial.”
In practice, patient age and functional status would figure heavily in deciding whether early valve replacement, and which procedure, is appropriate, Dr. Banovic said in an interview. Importantly, the trial’s patients were at low surgical risk and free of major chronic diseases or other important health concerns.
“Frailty and older age are known risk factors for suboptimal recovery” after SAVR, Dr. Banovic said when interviewed. Therefore, frail patients, who were not many in AVATAR, might be “more suitable for TAVR than SAVR, based on the TAVR-vs.-SAVR results in symptomatic AS patients,” he said.
“One might extrapolate experience from AVATAR trial to TAVR, which may lower the bar for TAVR indications,” but that would require more supporting evidence, Dr. Banovic said.
Confirmed asymptomatic
AVATAR, conducted at nine centers in seven countries in the European Union, randomly assigned 157 adults with severe AS by echocardiography and a LV ejection fraction (LVEF) greater than 50% to early SAVR or conservative management. They averaged 67 years in age, and 43% were women.
The trial excluded anyone with dyspnea, syncope, presyncope, angina, or LV dysfunction and anyone with a history of atrial fibrillation or significant cardiac, renal, or lung disease. The cohort’s average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 1.7%.
The 78 patients in the early-surgery group “were expected” to have the procedure within 8 weeks of randomization, the published report states; the median time was 55 days. Six of them ultimately did not have the surgery. There was only one periprocedural death, for an operative mortality of 1.4%.
The 79 patients assigned to conservative care were later referred for surgery if they developed symptoms, their LVEF dropped below 50%, or they showed a 0.3-m/sec jump in peak aortic jet velocity at follow-up echocardiography. That occurred with 25 patients a median of 400 days after randomization.
The rate of the primary endpoint – death from any cause, acute myocardial infarction, stroke, or unplanned HF hospitalization – was 16.6% in the early-surgery group and 32.9% for those managed conservatively over a median of 32 months. The hazard ratio by intention-to-treat analysis was 0.46 (95% confidence interval, 0.23-0.90; P = .02). The HR for death from any cause or HF hospitalization was 0.40 (95% CI, 0.19-0.84; P = .013). Any differences in the individual endpoints of death, first HF hospitalizations, thromboembolic complications, or major bleeding were not significant.
If early aortic valve replacement is better for patients like those in AVATAR, some sort of screening for previously unknown severe aortic stenosis may seem attractive for selected populations. “Echocardiography would be the screening test for aortic stenosis, but it’s fairly expensive and therefore has never been advocated as a test to screen everyone,” Dr. Pellikka observed.
“But things are changing,” given innovations such as point-of-care ultrasonography and machine learning, she noted. “Artificial intelligence is progressing in its application to echocardiography, and it’s conceivable that in the future, there might be some abbreviated or screening type of test. But I don’t think we’re quite there yet.”
Dr. Banovic had no conflicts; disclosures for the other authors are in the report. Dr. Delgado disclosed speaker fees from Edwards Lifesciences, Abbott Vascular, Medtronic, Merck, Novartis, and GE Healthcare and unrestricted research grants to her institution from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. Dr. Pellikka disclosed receiving a research grant from Ultromics and having unspecified modest relationships with GE Healthcare, Lantheus, and OxThera.
A version of this article first appeared on Medscape.com.
Better to intervene early with a new valve in patients with severe aortic stenosis (AS) who are asymptomatic, even during exercise, than to wait for the disease to progress and symptoms to emerge before operating, suggests a small, randomized trial that challenges the guidelines.
Of the trial’s 157 patients, all with negative results on stress tests and normal left ventricular (LV) function despite severe AS, those assigned to early surgical aortic valve replacement (SAVR), compared with standard watchful waiting, showed a better-than-50% drop in risk for death or major adverse cardiac events (MACE) over 2-3 years. The benefit appeared driven by fewer hospitalizations for heart failure (HF) and deaths in the early-surgery group.
The findings “advocate for early surgery once aortic stenosis becomes significant and regardless of symptom status,” Marko Banovic, MD, PhD, said during his presentation at the American Heart Association scientific sessions.
Dr. Banovic, from the University of Belgrade Medical School in Serbia, is coprincipal investigator on the trial, called AVATAR (Aortic Valve Replacement vs. Conservative Treatment in Asymptomatic Severe Aortic Stenosis). He is also lead author on the study’s publication in Circulation, timed to coincide with his AHA presentation.
“The AVATAR findings provide additional evidence to help clinicians in guiding their decision when seeing a patient with significant aortic stenosis, normal left ventricular function, overall low surgical risk, and without significant comorbidities,” Dr. Banovic told this news organization.
European and North American Guidelines favor watchful waiting for asymptomatic patients with severe aortic stenosis, with surgery upon development of symptoms or LV dysfunction, observed Victoria Delgado, MD, PhD, Leiden (the Netherlands) University Medical Center, an invited discussant for the AVATAR presentation.
AVATAR does suggest that “early surgery in truly asymptomatic patients with severe aortic stenosis and preserved ejection fraction seems to provide better outcomes as compared to the conservative treatment,” she said. “But I think that the long-term follow-up for potential events, such as valve durability or endocarditis, is still needed.”
The trial has strengths, compared with the recent RECOVERY trial, which also concluded in favor of early SAVR over watchful waiting in patients described as asymptomatic with severe aortic stenosis. Dr. Delgado and other observers, however, have pointed out limitations of that trial, including questions about whether the patients were truly asymptomatic – stress testing wasn›t routinely performed.
In AVATAR, all patients were negative at stress testing, which required them to reach their estimated maximum heart rate, Dr. Banovic noted. As he and his colleagues write, the trial expands on RECOVERY “by providing evidence of the benefit of early surgery in a setting representative of a dilemma in decision making, in truly asymptomatic patients with severe but not critical aortic stenosis and normal LV function.”
A role for TAVR?
Guidelines in general “can be very conservative and lag behind evidence a bit,” Patricia A. Pellikka, MD, Mayo Clinic, Rochester, Minn., who is not associated with AVATAR, said in an interview.
“I think when we see patients clinically, we can advise them that if they don’t have symptoms and they do have severe aortic stenosis,” she said, “they’re likely going to get symptoms within a reasonably short period of time, according to our retrospective databases, and that doing the intervention early may yield better long-term outcomes.”
The results of AVATAR, in which valve replacement consisted only of SAVR, “probably could be extrapolated” to transcatheter aortic valve replacement (TAVR), Dr. Pellikka observed. “Certainly, TAVR is the procedure that patients come asking for. It’s attractive to avoid a major surgery, and it seems very plausible that TAVR would have yielded similar results if that had been a therapy in this trial.”
In practice, patient age and functional status would figure heavily in deciding whether early valve replacement, and which procedure, is appropriate, Dr. Banovic said in an interview. Importantly, the trial’s patients were at low surgical risk and free of major chronic diseases or other important health concerns.
“Frailty and older age are known risk factors for suboptimal recovery” after SAVR, Dr. Banovic said when interviewed. Therefore, frail patients, who were not many in AVATAR, might be “more suitable for TAVR than SAVR, based on the TAVR-vs.-SAVR results in symptomatic AS patients,” he said.
“One might extrapolate experience from AVATAR trial to TAVR, which may lower the bar for TAVR indications,” but that would require more supporting evidence, Dr. Banovic said.
Confirmed asymptomatic
AVATAR, conducted at nine centers in seven countries in the European Union, randomly assigned 157 adults with severe AS by echocardiography and a LV ejection fraction (LVEF) greater than 50% to early SAVR or conservative management. They averaged 67 years in age, and 43% were women.
The trial excluded anyone with dyspnea, syncope, presyncope, angina, or LV dysfunction and anyone with a history of atrial fibrillation or significant cardiac, renal, or lung disease. The cohort’s average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 1.7%.
The 78 patients in the early-surgery group “were expected” to have the procedure within 8 weeks of randomization, the published report states; the median time was 55 days. Six of them ultimately did not have the surgery. There was only one periprocedural death, for an operative mortality of 1.4%.
The 79 patients assigned to conservative care were later referred for surgery if they developed symptoms, their LVEF dropped below 50%, or they showed a 0.3-m/sec jump in peak aortic jet velocity at follow-up echocardiography. That occurred with 25 patients a median of 400 days after randomization.
The rate of the primary endpoint – death from any cause, acute myocardial infarction, stroke, or unplanned HF hospitalization – was 16.6% in the early-surgery group and 32.9% for those managed conservatively over a median of 32 months. The hazard ratio by intention-to-treat analysis was 0.46 (95% confidence interval, 0.23-0.90; P = .02). The HR for death from any cause or HF hospitalization was 0.40 (95% CI, 0.19-0.84; P = .013). Any differences in the individual endpoints of death, first HF hospitalizations, thromboembolic complications, or major bleeding were not significant.
If early aortic valve replacement is better for patients like those in AVATAR, some sort of screening for previously unknown severe aortic stenosis may seem attractive for selected populations. “Echocardiography would be the screening test for aortic stenosis, but it’s fairly expensive and therefore has never been advocated as a test to screen everyone,” Dr. Pellikka observed.
“But things are changing,” given innovations such as point-of-care ultrasonography and machine learning, she noted. “Artificial intelligence is progressing in its application to echocardiography, and it’s conceivable that in the future, there might be some abbreviated or screening type of test. But I don’t think we’re quite there yet.”
Dr. Banovic had no conflicts; disclosures for the other authors are in the report. Dr. Delgado disclosed speaker fees from Edwards Lifesciences, Abbott Vascular, Medtronic, Merck, Novartis, and GE Healthcare and unrestricted research grants to her institution from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. Dr. Pellikka disclosed receiving a research grant from Ultromics and having unspecified modest relationships with GE Healthcare, Lantheus, and OxThera.
A version of this article first appeared on Medscape.com.
FROM AHA 2021
CABG safe 3 days after stopping ticagrelor: RAPID CABG
Patients with acute coronary syndromes who have been taking the antiplatelet medication, ticagrelor, and who need coronary artery bypass surgery (CABG) may be able to safely have the procedure earlier than typically recommended, a new randomized trial suggests.
The RAPID CABG trial found that early surgery 2-3 days after ticagrelor cessation was noninferior in incurring severe or massive perioperative bleeding, compared with waiting 5-7 days. There was also no significant difference in TIMI CABG or Bleeding Academic Research Consortium (BARC) type 4 or 5 bleeding.
Patients in the delayed group had a numerically higher number of ischemic events requiring earlier surgery and had a longer hospital stay.
The study was presented at the American Heart Association scientific sessions.
“RAPID CABG is the first and only randomized controlled trial evaluating the safety of early surgery in patients taking ticagrelor,” said lead investigator Derek So, MD.
Dr. So, a cardiologist at the University of Ottawa Heart Institute and a professor at the University of Ottawa, explained that ticagrelor is a first-line antiplatelet agent for patients with acute coronary syndromes (ACS), but around 10% of patients presenting with ACS require CABG surgery.
A major concern among patients requiring bypass surgery is perioperative bleeding, and it has been shown that patients undergoing urgent bypass within 24 hours of the last dose of ticagrelor have increased mortality. Accordingly, guidelines suggest a waiting period for patients not requiring urgent bypass surgery, Dr. So noted.
Current North American guidelines suggest a waiting period of at least 5 days after stopping ticagrelor before bypass surgery. In contrast, the updated European and Japanese guidelines suggest a waiting period of 3 days.
Dr. So noted that all of the guidelines are based on cohort studies and pharmacodynamic studies, with no randomized evidence. Pharmacodynamic studies have shown that at 48 hours after the last dose of ticagrelor, the level of platelet inhibition drops to the same levels seen with long-term treatment with clopidogrel, a weaker antiplatelet drug, and after 120 hours (5 days) the effect has completely worn off.
Dr. So concluded that these new results from the RAPID CABG trial “may influence future iterations of North American guidelines with reduced waiting prior to bypass surgery” for patients receiving ticagrelor, and “they could also strengthen the level of evidence in European and Asian guidelines.”
Designated discussant of the RAPID CABG trial, Roxana Mehran, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, said this was a “very important study,” being the only randomized trial to look at this issue to date.
Dr. Mehran noted that the results showed a similar number of major life-threatening bleeding events in the early and delayed groups and met the noninferiority endpoint, but she pointed out that the trial had a small sample size and a small number of events. “Therefore, larger trials are needed to verify these important and encouraging results.”
However, she concluded that these results should be considered in decisions about the timing of bypass surgery in patients receiving ticagrelor. “I will be changing my practice and sending patients earlier based on this data,” she said.
RAPID CABG
RAPID CABG was a physician-initiated multicenter randomized study evaluating the safety of early surgery at 2-3 days after ticagrelor cessation, compared with a delay of 5-7 days among patients presenting with ACS who required nonemergency CABG surgery.
The study enrolled 143 patients with ACS who were receiving ticagrelor and needed CABG surgery. Patients with stenting for culprit lesions, those requiring urgent surgery (less than 24 hours after presentation), and those requiring valve surgery were excluded.
Three patients declined surgery, and several others underwent surgery outside the assigned time window, so the results were based on the per protocol analysis of patients who actually had CABG in the assigned time window: 65 patients in the early CABG group and 58 in the delayed group.
The mean time from last ticagrelor dose to surgery was 3 days in the early group and 6 days in the delayed group.
Platelet reactivity on the VerifyNow test showed more residual antiplatelet activity in the early group, with P2Y12 reaction unit (PRU) levels of 200 (vs. 251 in the delayed group). This test measures the extent of platelet aggregation in the presence of P2Y12-inhibitor drugs, with lower PRU levels showing stronger antiplatelet effects.
The primary outcome of the study was severe or massive bleeding by Universal Definition of Perioperative Bleeding (UDPB) class 3 or 4. This is defined as a blood transfusions of more than 5 units of red blood cells or plasma within 24 hours of surgical closure, chest tube drainage of over 1,000 mL in the first 12 hours, and reoperation for bleeding.
Results showed that 4.6% of the early-surgery group had a primary outcome bleeding event, compared with 5.2% of the delayed surgery group, meeting the criteria for noninferiority (P = .0253 for noninferiority).
Individual components of the primary endpoint showed three class 3 (severe) bleeding events in both groups and no class 4 (massive) bleeding events in either group.
In terms of other bleeding outcomes, TIMI CABG bleeding occurred in two patients (3.1%) in the early-surgery group vs. no patients in the delayed group; BARC 4 bleeding occurred in two patients (3.1%) in the early group versus none in the delayed group, and there were no BARC 5 bleeding events in either group.
In the intention-to-treat analysis, ischemic events before surgery occurred in six patients (8.7%) in the delayed group (one myocardial infarction, four cases of recurrent ischemia, and one ventricular tachycardia) versus none in the early group.
Cumulative 6-month ischemic events occurred in nine patients (13.0%) in the delayed group vs. four patients (5.6%) in the early group, the difference being driven by nonfatal MI and recurrent ischemia.
There were no cardiovascular deaths in either group and one all-cause death in both groups.
Patients undergoing early surgery also had a shorter hospitalization, with a median length of stay of 9 days versus 12 days in the delayed group.
Larger trial needed
Commenting on the RAPID CABG study at an AHA press conference, Joanna Chikwe, MD, chair of the cardiac surgery department at Cedars-Sinai Medical Center, Los Angeles, said the results were in line with her practice.
“These results confirm what I already think is safe,” she said. “I’m comfortable going within 48 hours. But we individualize our approach, so it was helpful that the study investigators included platelet reactivity data. The interesting thing for me in this study was the number of adverse events in patients who waited longer.”
Dr. Chikwe said her top-line message was that “Surgery looked incredibly safe; there was amazingly low mortality. And if a patient has an indication for surgery, waiting does not serve you well.”
However, she also cautioned that the trial was somewhat underpowered, with a small number of events that drove the primary outcome, leading to some uncertainty on the results.
“The RAPID trial was helpful, and although it confirms my practice, I think physicians may want to see a larger-powered trial to be convincingly compelled that they should change their practice,” Dr. Chikwe noted.
She added that clinical trials in cardiac surgery are driven by inherent challenges. “Cardiac surgery is not very common, and it is hard to recruit patients into these trials, so you are generally tied to a small number of patients, and you therefore have to be extremely thoughtful about the study design. It is almost a given that you will need to use surrogate endpoints, and the choice of the surrogate endpoint can determine which way the trial goes.”
The RAPID CABG study was funded by the Canadian Institutes of Health Research. Dr. So reports research support, consultancy, or speaker’s fees from AggreDyne, Roche Diagnostics, Fujimori Kogyo, and AstraZeneca Canada. Dr. Mehran reports that her institution has received significant trial funding from AstraZeneca (the manufacturer of ticagrelor).
A version of this article first appeared on Medscape.com.
Patients with acute coronary syndromes who have been taking the antiplatelet medication, ticagrelor, and who need coronary artery bypass surgery (CABG) may be able to safely have the procedure earlier than typically recommended, a new randomized trial suggests.
The RAPID CABG trial found that early surgery 2-3 days after ticagrelor cessation was noninferior in incurring severe or massive perioperative bleeding, compared with waiting 5-7 days. There was also no significant difference in TIMI CABG or Bleeding Academic Research Consortium (BARC) type 4 or 5 bleeding.
Patients in the delayed group had a numerically higher number of ischemic events requiring earlier surgery and had a longer hospital stay.
The study was presented at the American Heart Association scientific sessions.
“RAPID CABG is the first and only randomized controlled trial evaluating the safety of early surgery in patients taking ticagrelor,” said lead investigator Derek So, MD.
Dr. So, a cardiologist at the University of Ottawa Heart Institute and a professor at the University of Ottawa, explained that ticagrelor is a first-line antiplatelet agent for patients with acute coronary syndromes (ACS), but around 10% of patients presenting with ACS require CABG surgery.
A major concern among patients requiring bypass surgery is perioperative bleeding, and it has been shown that patients undergoing urgent bypass within 24 hours of the last dose of ticagrelor have increased mortality. Accordingly, guidelines suggest a waiting period for patients not requiring urgent bypass surgery, Dr. So noted.
Current North American guidelines suggest a waiting period of at least 5 days after stopping ticagrelor before bypass surgery. In contrast, the updated European and Japanese guidelines suggest a waiting period of 3 days.
Dr. So noted that all of the guidelines are based on cohort studies and pharmacodynamic studies, with no randomized evidence. Pharmacodynamic studies have shown that at 48 hours after the last dose of ticagrelor, the level of platelet inhibition drops to the same levels seen with long-term treatment with clopidogrel, a weaker antiplatelet drug, and after 120 hours (5 days) the effect has completely worn off.
Dr. So concluded that these new results from the RAPID CABG trial “may influence future iterations of North American guidelines with reduced waiting prior to bypass surgery” for patients receiving ticagrelor, and “they could also strengthen the level of evidence in European and Asian guidelines.”
Designated discussant of the RAPID CABG trial, Roxana Mehran, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, said this was a “very important study,” being the only randomized trial to look at this issue to date.
Dr. Mehran noted that the results showed a similar number of major life-threatening bleeding events in the early and delayed groups and met the noninferiority endpoint, but she pointed out that the trial had a small sample size and a small number of events. “Therefore, larger trials are needed to verify these important and encouraging results.”
However, she concluded that these results should be considered in decisions about the timing of bypass surgery in patients receiving ticagrelor. “I will be changing my practice and sending patients earlier based on this data,” she said.
RAPID CABG
RAPID CABG was a physician-initiated multicenter randomized study evaluating the safety of early surgery at 2-3 days after ticagrelor cessation, compared with a delay of 5-7 days among patients presenting with ACS who required nonemergency CABG surgery.
The study enrolled 143 patients with ACS who were receiving ticagrelor and needed CABG surgery. Patients with stenting for culprit lesions, those requiring urgent surgery (less than 24 hours after presentation), and those requiring valve surgery were excluded.
Three patients declined surgery, and several others underwent surgery outside the assigned time window, so the results were based on the per protocol analysis of patients who actually had CABG in the assigned time window: 65 patients in the early CABG group and 58 in the delayed group.
The mean time from last ticagrelor dose to surgery was 3 days in the early group and 6 days in the delayed group.
Platelet reactivity on the VerifyNow test showed more residual antiplatelet activity in the early group, with P2Y12 reaction unit (PRU) levels of 200 (vs. 251 in the delayed group). This test measures the extent of platelet aggregation in the presence of P2Y12-inhibitor drugs, with lower PRU levels showing stronger antiplatelet effects.
The primary outcome of the study was severe or massive bleeding by Universal Definition of Perioperative Bleeding (UDPB) class 3 or 4. This is defined as a blood transfusions of more than 5 units of red blood cells or plasma within 24 hours of surgical closure, chest tube drainage of over 1,000 mL in the first 12 hours, and reoperation for bleeding.
Results showed that 4.6% of the early-surgery group had a primary outcome bleeding event, compared with 5.2% of the delayed surgery group, meeting the criteria for noninferiority (P = .0253 for noninferiority).
Individual components of the primary endpoint showed three class 3 (severe) bleeding events in both groups and no class 4 (massive) bleeding events in either group.
In terms of other bleeding outcomes, TIMI CABG bleeding occurred in two patients (3.1%) in the early-surgery group vs. no patients in the delayed group; BARC 4 bleeding occurred in two patients (3.1%) in the early group versus none in the delayed group, and there were no BARC 5 bleeding events in either group.
In the intention-to-treat analysis, ischemic events before surgery occurred in six patients (8.7%) in the delayed group (one myocardial infarction, four cases of recurrent ischemia, and one ventricular tachycardia) versus none in the early group.
Cumulative 6-month ischemic events occurred in nine patients (13.0%) in the delayed group vs. four patients (5.6%) in the early group, the difference being driven by nonfatal MI and recurrent ischemia.
There were no cardiovascular deaths in either group and one all-cause death in both groups.
Patients undergoing early surgery also had a shorter hospitalization, with a median length of stay of 9 days versus 12 days in the delayed group.
Larger trial needed
Commenting on the RAPID CABG study at an AHA press conference, Joanna Chikwe, MD, chair of the cardiac surgery department at Cedars-Sinai Medical Center, Los Angeles, said the results were in line with her practice.
“These results confirm what I already think is safe,” she said. “I’m comfortable going within 48 hours. But we individualize our approach, so it was helpful that the study investigators included platelet reactivity data. The interesting thing for me in this study was the number of adverse events in patients who waited longer.”
Dr. Chikwe said her top-line message was that “Surgery looked incredibly safe; there was amazingly low mortality. And if a patient has an indication for surgery, waiting does not serve you well.”
However, she also cautioned that the trial was somewhat underpowered, with a small number of events that drove the primary outcome, leading to some uncertainty on the results.
“The RAPID trial was helpful, and although it confirms my practice, I think physicians may want to see a larger-powered trial to be convincingly compelled that they should change their practice,” Dr. Chikwe noted.
She added that clinical trials in cardiac surgery are driven by inherent challenges. “Cardiac surgery is not very common, and it is hard to recruit patients into these trials, so you are generally tied to a small number of patients, and you therefore have to be extremely thoughtful about the study design. It is almost a given that you will need to use surrogate endpoints, and the choice of the surrogate endpoint can determine which way the trial goes.”
The RAPID CABG study was funded by the Canadian Institutes of Health Research. Dr. So reports research support, consultancy, or speaker’s fees from AggreDyne, Roche Diagnostics, Fujimori Kogyo, and AstraZeneca Canada. Dr. Mehran reports that her institution has received significant trial funding from AstraZeneca (the manufacturer of ticagrelor).
A version of this article first appeared on Medscape.com.
Patients with acute coronary syndromes who have been taking the antiplatelet medication, ticagrelor, and who need coronary artery bypass surgery (CABG) may be able to safely have the procedure earlier than typically recommended, a new randomized trial suggests.
The RAPID CABG trial found that early surgery 2-3 days after ticagrelor cessation was noninferior in incurring severe or massive perioperative bleeding, compared with waiting 5-7 days. There was also no significant difference in TIMI CABG or Bleeding Academic Research Consortium (BARC) type 4 or 5 bleeding.
Patients in the delayed group had a numerically higher number of ischemic events requiring earlier surgery and had a longer hospital stay.
The study was presented at the American Heart Association scientific sessions.
“RAPID CABG is the first and only randomized controlled trial evaluating the safety of early surgery in patients taking ticagrelor,” said lead investigator Derek So, MD.
Dr. So, a cardiologist at the University of Ottawa Heart Institute and a professor at the University of Ottawa, explained that ticagrelor is a first-line antiplatelet agent for patients with acute coronary syndromes (ACS), but around 10% of patients presenting with ACS require CABG surgery.
A major concern among patients requiring bypass surgery is perioperative bleeding, and it has been shown that patients undergoing urgent bypass within 24 hours of the last dose of ticagrelor have increased mortality. Accordingly, guidelines suggest a waiting period for patients not requiring urgent bypass surgery, Dr. So noted.
Current North American guidelines suggest a waiting period of at least 5 days after stopping ticagrelor before bypass surgery. In contrast, the updated European and Japanese guidelines suggest a waiting period of 3 days.
Dr. So noted that all of the guidelines are based on cohort studies and pharmacodynamic studies, with no randomized evidence. Pharmacodynamic studies have shown that at 48 hours after the last dose of ticagrelor, the level of platelet inhibition drops to the same levels seen with long-term treatment with clopidogrel, a weaker antiplatelet drug, and after 120 hours (5 days) the effect has completely worn off.
Dr. So concluded that these new results from the RAPID CABG trial “may influence future iterations of North American guidelines with reduced waiting prior to bypass surgery” for patients receiving ticagrelor, and “they could also strengthen the level of evidence in European and Asian guidelines.”
Designated discussant of the RAPID CABG trial, Roxana Mehran, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, said this was a “very important study,” being the only randomized trial to look at this issue to date.
Dr. Mehran noted that the results showed a similar number of major life-threatening bleeding events in the early and delayed groups and met the noninferiority endpoint, but she pointed out that the trial had a small sample size and a small number of events. “Therefore, larger trials are needed to verify these important and encouraging results.”
However, she concluded that these results should be considered in decisions about the timing of bypass surgery in patients receiving ticagrelor. “I will be changing my practice and sending patients earlier based on this data,” she said.
RAPID CABG
RAPID CABG was a physician-initiated multicenter randomized study evaluating the safety of early surgery at 2-3 days after ticagrelor cessation, compared with a delay of 5-7 days among patients presenting with ACS who required nonemergency CABG surgery.
The study enrolled 143 patients with ACS who were receiving ticagrelor and needed CABG surgery. Patients with stenting for culprit lesions, those requiring urgent surgery (less than 24 hours after presentation), and those requiring valve surgery were excluded.
Three patients declined surgery, and several others underwent surgery outside the assigned time window, so the results were based on the per protocol analysis of patients who actually had CABG in the assigned time window: 65 patients in the early CABG group and 58 in the delayed group.
The mean time from last ticagrelor dose to surgery was 3 days in the early group and 6 days in the delayed group.
Platelet reactivity on the VerifyNow test showed more residual antiplatelet activity in the early group, with P2Y12 reaction unit (PRU) levels of 200 (vs. 251 in the delayed group). This test measures the extent of platelet aggregation in the presence of P2Y12-inhibitor drugs, with lower PRU levels showing stronger antiplatelet effects.
The primary outcome of the study was severe or massive bleeding by Universal Definition of Perioperative Bleeding (UDPB) class 3 or 4. This is defined as a blood transfusions of more than 5 units of red blood cells or plasma within 24 hours of surgical closure, chest tube drainage of over 1,000 mL in the first 12 hours, and reoperation for bleeding.
Results showed that 4.6% of the early-surgery group had a primary outcome bleeding event, compared with 5.2% of the delayed surgery group, meeting the criteria for noninferiority (P = .0253 for noninferiority).
Individual components of the primary endpoint showed three class 3 (severe) bleeding events in both groups and no class 4 (massive) bleeding events in either group.
In terms of other bleeding outcomes, TIMI CABG bleeding occurred in two patients (3.1%) in the early-surgery group vs. no patients in the delayed group; BARC 4 bleeding occurred in two patients (3.1%) in the early group versus none in the delayed group, and there were no BARC 5 bleeding events in either group.
In the intention-to-treat analysis, ischemic events before surgery occurred in six patients (8.7%) in the delayed group (one myocardial infarction, four cases of recurrent ischemia, and one ventricular tachycardia) versus none in the early group.
Cumulative 6-month ischemic events occurred in nine patients (13.0%) in the delayed group vs. four patients (5.6%) in the early group, the difference being driven by nonfatal MI and recurrent ischemia.
There were no cardiovascular deaths in either group and one all-cause death in both groups.
Patients undergoing early surgery also had a shorter hospitalization, with a median length of stay of 9 days versus 12 days in the delayed group.
Larger trial needed
Commenting on the RAPID CABG study at an AHA press conference, Joanna Chikwe, MD, chair of the cardiac surgery department at Cedars-Sinai Medical Center, Los Angeles, said the results were in line with her practice.
“These results confirm what I already think is safe,” she said. “I’m comfortable going within 48 hours. But we individualize our approach, so it was helpful that the study investigators included platelet reactivity data. The interesting thing for me in this study was the number of adverse events in patients who waited longer.”
Dr. Chikwe said her top-line message was that “Surgery looked incredibly safe; there was amazingly low mortality. And if a patient has an indication for surgery, waiting does not serve you well.”
However, she also cautioned that the trial was somewhat underpowered, with a small number of events that drove the primary outcome, leading to some uncertainty on the results.
“The RAPID trial was helpful, and although it confirms my practice, I think physicians may want to see a larger-powered trial to be convincingly compelled that they should change their practice,” Dr. Chikwe noted.
She added that clinical trials in cardiac surgery are driven by inherent challenges. “Cardiac surgery is not very common, and it is hard to recruit patients into these trials, so you are generally tied to a small number of patients, and you therefore have to be extremely thoughtful about the study design. It is almost a given that you will need to use surrogate endpoints, and the choice of the surrogate endpoint can determine which way the trial goes.”
The RAPID CABG study was funded by the Canadian Institutes of Health Research. Dr. So reports research support, consultancy, or speaker’s fees from AggreDyne, Roche Diagnostics, Fujimori Kogyo, and AstraZeneca Canada. Dr. Mehran reports that her institution has received significant trial funding from AstraZeneca (the manufacturer of ticagrelor).
A version of this article first appeared on Medscape.com.
FROM AHA 2021
Concomitant tricuspid-mitral surgery beneficial but with a trade-off
Tricuspid valve repair at the time of mitral valve surgery reduces tricuspid regurgitation progression, but at the cost of more than a fivefold increase in permanent pacemakers, results of a new Cardiothoracic Surgical Trials Network study show.
The results were presented during the opening late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.
Tricuspid regurgitation (TR) is common among patients undergoing mitral valve surgery, and there’s broad agreement to intervene when a patient has severe TR. There’s uncertainty, however, about the management of moderate or less TR during mitral valve surgery, which is reflected in current guidelines on the basis of observational data, explained coprimary investigator James Gammie, MD, codirector and surgical director of the Johns Hopkins Heart and Vascular Institute, Baltimore. As a result, rates of concomitant tricuspid-mitral surgery range from 5% to 75% at various centers.
To help fill the gap, Dr. Gammie and colleagues screened 5,208 patients at 29 centers in the United States, Canada, and Germany undergoing surgery for degenerative mitral regurgitation, and randomly assigned 401 patients (75% male) to mitral valve surgery alone or with tricuspid annuloplasty.
Patients had either moderate TR (37%) or less than moderate TR with a dilated tricuspid annulus of at least 40 mm or at least 21 mm/m2 indexed for body surface area. Importantly, there was a uniform surgical approach using undersized (26-30 mm) rigid nonplanar annuloplasty rings to repair the tricuspid valve, he said.
The study’s primary outcome of treatment failure at 2 years was defined as the composite of death, reoperation for TR, or progression of TR from baseline by 2 grades or severe TR.
The primary endpoint occurred in 10.2% of patients who underwent mitral valve surgery alone and 3.9% who underwent concomitant tricuspid annuloplasty (relative risk, 0.37; 95% confidence interval, 0.16-0.86; P = .02).
The endpoint was driven exclusively by less TR progression in the annuloplasty group, with no TR reoperations in either group, observed Dr. Gammie. At 2 years, just 0.6% of the annuloplasty group had severe TR, compared with 5.6% of the surgery-alone group.
The rate of permanent pacemaker implantations, however, jumped from 2.5% with surgery alone to 14.1% with concomitant tricuspid annuloplasty (rate ratio, 5.75; 95% CI, 2.27-14.60). More than half of pacemakers were placed during the first 2 days after surgery.
There was no between-group difference in 2-year rates of all-cause mortality, major adverse cardiac and cerebrovascular events, readmission, quality of life, or functional status.
Less than moderate TR
In a post hoc analysis stratified by baseline TR severity, treatment failure was significantly less common with surgery plus tricuspid annuloplasty among patients with moderate TR (4.5% vs. 18.1%) but not among those with less than moderate TR and tricuspid annular dilation (3.4% vs. 6.1%).
Although the trial was not powered for the subgroup analysis, “these results call into question the idea that less than moderate TR with annular dilation should be an indication for tricuspid valve repair,” Dr. Gammie told this news organization.
“I did not repair the tricuspid valve in the setting of less than moderate TR before the trial, and my practice won’t change; but it will be based on much better evidence,” he added. “Of course, long-term data from our trial will be of great interest.”
Discussant Joseph Woo, MD, chair of surgery at Stanford (Calif.) University, congratulated the authors on a “landmark trial” that addresses a highly relevant problem without a clear-cut indication.
In the 2020 AHA/American College of Cardiology heart valve disease guideline, tricuspid valve surgery is a class I recommendation when there’s severe TR (stages C and D) and left-sided valve surgery but a class IIa recommendation in patients with progressive TR (stage B) with an annular dilation of at least 40 mm.
“The interesting findings in this study include that moderate TR was only 37% of the enrolled patients, and only 97% of the patients with degenerative MR received a mitral valve repair,” Dr. Woo said. “This level of mitral valve repair is perhaps lower than what we might expect at these centers and lower, certainly, than what the AHA/ACC guidelines recommend for surgery on asymptomatic severe mitral regurgitation.”
Panelist Roxanna Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York said, “What I was struck by is that we, as clinicians, believe that if you fix the mitral valve, maybe the tricuspid regurgitation will improve. And it seems like that is not what’s happening, and I think that’s a big takeaway.”
Session comoderator Joanna Chikwe, MD, head of cardiac surgery at Cedars-Sinai Medical Center, Los Angeles, said, “I think we can all agree that severe tricuspid regurgitation is a disaster for patients, and I think the fact the trial is designed for an additional 5 years’ follow-up will hopefully give us some insights into the clinical impact of severe tricuspid regurgitation.”
For now, “a back of the envelope calculation suggests that, for every 20 patients with moderate tricuspid regurgitation who we repair the tricuspid valve in, we would prevent severe tricuspid valve regurgitation in 1 at the price of pacemakers in 2,” she said.
Dr. Chikwe said in an interview that “transcatheter tricuspid repair is increasingly helping these patients, but if you could avoid it with a technique that doesn’t cause incremental harm beyond, perhaps, the need for pacemakers, then this is helpful data that supports that approach.”
The pacemaker burden is not negligible, she said, but also not surprising to surgeons. “If you look at national practice of mitral-tricuspid surgery, it’s about 15% after that, and it’s simply because the conduction tissue is so close to the tricuspid annulus.”
Pacemaker implantation rates, like those for concomitant tricuspid-mitral surgery, are also highly variable, and in some single-center series only around 2%, Dr. Chikwe said. “So that suggests there are technical approaches that can minimize the pacemaker rate [such as] being extremely careful to avoid suture placement around the area of the conduction tissues.”
For some the trade-off between reduced TR progression and the risk of a permanent pacemaker is worth it. “But the fact that the trial didn’t show a difference in survival, a difference in symptoms or quality of life, might suggest that patients you anticipated were high risk for surgery or didn’t have a longer projected survival aren’t going to benefit from what is quite an aggressive surgical approach,” Dr. Chikwe said.
In an accompanying editorial, Dr. Chikwe and Mario Gaudino, MD, of Weill Cornell Medicine, New York, also point out that the “very dynamic nature of tricuspid regurgitation and wide variability in assessing tricuspid annular dilatation are additional compelling reasons to leave lesser regurgitation alone.”
Julia Grapsa, MD, PhD, Kings College and tricuspid service lead at Guys and St. Thomas NHS, London, also pointed to the need for longer-term follow-up but said increased use of imaging markers is also needed to help pinpoint TR progression in these patients. “For the moment, the results should remind imagers and clinicians to refer patients earlier.”
“As a valvular heart physician, I see more and more patients coming in with significant severe tricuspid regurgitation post–mitral valve surgery and because of the time that’s passed, there’s dysfunction of the right heart, the left heart, and it’s very hard to suggest an operation because they’re at high risk,” she said. “So we’re discussing with these patients whether to do an intervention or medical management.”
“Now, with this study, and the pending longer follow-up by the authors, I’m optimistic that the class II recommendation will be class I in order to help our patients treat tricuspid regurgitation earlier than late,” said Dr. Grapsa, who is also editor-in-chief of JACC: Case Reports.
The study was funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research. Dr. Gammie reports a consultant/stockholder relationship with Edwards Lifesciences. Dr. Grapsa reports no conflicts of interest. Dr. Chikwe reports that as coprincipal investigator/study director of NCT 05051033 (an NHLBI-sponsored Cardiothoracic Surgical Trials Network trial), she collaborates with several of the study authors.
A version of this article first appeared on Medscape.com.
Tricuspid valve repair at the time of mitral valve surgery reduces tricuspid regurgitation progression, but at the cost of more than a fivefold increase in permanent pacemakers, results of a new Cardiothoracic Surgical Trials Network study show.
The results were presented during the opening late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.
Tricuspid regurgitation (TR) is common among patients undergoing mitral valve surgery, and there’s broad agreement to intervene when a patient has severe TR. There’s uncertainty, however, about the management of moderate or less TR during mitral valve surgery, which is reflected in current guidelines on the basis of observational data, explained coprimary investigator James Gammie, MD, codirector and surgical director of the Johns Hopkins Heart and Vascular Institute, Baltimore. As a result, rates of concomitant tricuspid-mitral surgery range from 5% to 75% at various centers.
To help fill the gap, Dr. Gammie and colleagues screened 5,208 patients at 29 centers in the United States, Canada, and Germany undergoing surgery for degenerative mitral regurgitation, and randomly assigned 401 patients (75% male) to mitral valve surgery alone or with tricuspid annuloplasty.
Patients had either moderate TR (37%) or less than moderate TR with a dilated tricuspid annulus of at least 40 mm or at least 21 mm/m2 indexed for body surface area. Importantly, there was a uniform surgical approach using undersized (26-30 mm) rigid nonplanar annuloplasty rings to repair the tricuspid valve, he said.
The study’s primary outcome of treatment failure at 2 years was defined as the composite of death, reoperation for TR, or progression of TR from baseline by 2 grades or severe TR.
The primary endpoint occurred in 10.2% of patients who underwent mitral valve surgery alone and 3.9% who underwent concomitant tricuspid annuloplasty (relative risk, 0.37; 95% confidence interval, 0.16-0.86; P = .02).
The endpoint was driven exclusively by less TR progression in the annuloplasty group, with no TR reoperations in either group, observed Dr. Gammie. At 2 years, just 0.6% of the annuloplasty group had severe TR, compared with 5.6% of the surgery-alone group.
The rate of permanent pacemaker implantations, however, jumped from 2.5% with surgery alone to 14.1% with concomitant tricuspid annuloplasty (rate ratio, 5.75; 95% CI, 2.27-14.60). More than half of pacemakers were placed during the first 2 days after surgery.
There was no between-group difference in 2-year rates of all-cause mortality, major adverse cardiac and cerebrovascular events, readmission, quality of life, or functional status.
Less than moderate TR
In a post hoc analysis stratified by baseline TR severity, treatment failure was significantly less common with surgery plus tricuspid annuloplasty among patients with moderate TR (4.5% vs. 18.1%) but not among those with less than moderate TR and tricuspid annular dilation (3.4% vs. 6.1%).
Although the trial was not powered for the subgroup analysis, “these results call into question the idea that less than moderate TR with annular dilation should be an indication for tricuspid valve repair,” Dr. Gammie told this news organization.
“I did not repair the tricuspid valve in the setting of less than moderate TR before the trial, and my practice won’t change; but it will be based on much better evidence,” he added. “Of course, long-term data from our trial will be of great interest.”
Discussant Joseph Woo, MD, chair of surgery at Stanford (Calif.) University, congratulated the authors on a “landmark trial” that addresses a highly relevant problem without a clear-cut indication.
In the 2020 AHA/American College of Cardiology heart valve disease guideline, tricuspid valve surgery is a class I recommendation when there’s severe TR (stages C and D) and left-sided valve surgery but a class IIa recommendation in patients with progressive TR (stage B) with an annular dilation of at least 40 mm.
“The interesting findings in this study include that moderate TR was only 37% of the enrolled patients, and only 97% of the patients with degenerative MR received a mitral valve repair,” Dr. Woo said. “This level of mitral valve repair is perhaps lower than what we might expect at these centers and lower, certainly, than what the AHA/ACC guidelines recommend for surgery on asymptomatic severe mitral regurgitation.”
Panelist Roxanna Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York said, “What I was struck by is that we, as clinicians, believe that if you fix the mitral valve, maybe the tricuspid regurgitation will improve. And it seems like that is not what’s happening, and I think that’s a big takeaway.”
Session comoderator Joanna Chikwe, MD, head of cardiac surgery at Cedars-Sinai Medical Center, Los Angeles, said, “I think we can all agree that severe tricuspid regurgitation is a disaster for patients, and I think the fact the trial is designed for an additional 5 years’ follow-up will hopefully give us some insights into the clinical impact of severe tricuspid regurgitation.”
For now, “a back of the envelope calculation suggests that, for every 20 patients with moderate tricuspid regurgitation who we repair the tricuspid valve in, we would prevent severe tricuspid valve regurgitation in 1 at the price of pacemakers in 2,” she said.
Dr. Chikwe said in an interview that “transcatheter tricuspid repair is increasingly helping these patients, but if you could avoid it with a technique that doesn’t cause incremental harm beyond, perhaps, the need for pacemakers, then this is helpful data that supports that approach.”
The pacemaker burden is not negligible, she said, but also not surprising to surgeons. “If you look at national practice of mitral-tricuspid surgery, it’s about 15% after that, and it’s simply because the conduction tissue is so close to the tricuspid annulus.”
Pacemaker implantation rates, like those for concomitant tricuspid-mitral surgery, are also highly variable, and in some single-center series only around 2%, Dr. Chikwe said. “So that suggests there are technical approaches that can minimize the pacemaker rate [such as] being extremely careful to avoid suture placement around the area of the conduction tissues.”
For some the trade-off between reduced TR progression and the risk of a permanent pacemaker is worth it. “But the fact that the trial didn’t show a difference in survival, a difference in symptoms or quality of life, might suggest that patients you anticipated were high risk for surgery or didn’t have a longer projected survival aren’t going to benefit from what is quite an aggressive surgical approach,” Dr. Chikwe said.
In an accompanying editorial, Dr. Chikwe and Mario Gaudino, MD, of Weill Cornell Medicine, New York, also point out that the “very dynamic nature of tricuspid regurgitation and wide variability in assessing tricuspid annular dilatation are additional compelling reasons to leave lesser regurgitation alone.”
Julia Grapsa, MD, PhD, Kings College and tricuspid service lead at Guys and St. Thomas NHS, London, also pointed to the need for longer-term follow-up but said increased use of imaging markers is also needed to help pinpoint TR progression in these patients. “For the moment, the results should remind imagers and clinicians to refer patients earlier.”
“As a valvular heart physician, I see more and more patients coming in with significant severe tricuspid regurgitation post–mitral valve surgery and because of the time that’s passed, there’s dysfunction of the right heart, the left heart, and it’s very hard to suggest an operation because they’re at high risk,” she said. “So we’re discussing with these patients whether to do an intervention or medical management.”
“Now, with this study, and the pending longer follow-up by the authors, I’m optimistic that the class II recommendation will be class I in order to help our patients treat tricuspid regurgitation earlier than late,” said Dr. Grapsa, who is also editor-in-chief of JACC: Case Reports.
The study was funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research. Dr. Gammie reports a consultant/stockholder relationship with Edwards Lifesciences. Dr. Grapsa reports no conflicts of interest. Dr. Chikwe reports that as coprincipal investigator/study director of NCT 05051033 (an NHLBI-sponsored Cardiothoracic Surgical Trials Network trial), she collaborates with several of the study authors.
A version of this article first appeared on Medscape.com.
Tricuspid valve repair at the time of mitral valve surgery reduces tricuspid regurgitation progression, but at the cost of more than a fivefold increase in permanent pacemakers, results of a new Cardiothoracic Surgical Trials Network study show.
The results were presented during the opening late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.
Tricuspid regurgitation (TR) is common among patients undergoing mitral valve surgery, and there’s broad agreement to intervene when a patient has severe TR. There’s uncertainty, however, about the management of moderate or less TR during mitral valve surgery, which is reflected in current guidelines on the basis of observational data, explained coprimary investigator James Gammie, MD, codirector and surgical director of the Johns Hopkins Heart and Vascular Institute, Baltimore. As a result, rates of concomitant tricuspid-mitral surgery range from 5% to 75% at various centers.
To help fill the gap, Dr. Gammie and colleagues screened 5,208 patients at 29 centers in the United States, Canada, and Germany undergoing surgery for degenerative mitral regurgitation, and randomly assigned 401 patients (75% male) to mitral valve surgery alone or with tricuspid annuloplasty.
Patients had either moderate TR (37%) or less than moderate TR with a dilated tricuspid annulus of at least 40 mm or at least 21 mm/m2 indexed for body surface area. Importantly, there was a uniform surgical approach using undersized (26-30 mm) rigid nonplanar annuloplasty rings to repair the tricuspid valve, he said.
The study’s primary outcome of treatment failure at 2 years was defined as the composite of death, reoperation for TR, or progression of TR from baseline by 2 grades or severe TR.
The primary endpoint occurred in 10.2% of patients who underwent mitral valve surgery alone and 3.9% who underwent concomitant tricuspid annuloplasty (relative risk, 0.37; 95% confidence interval, 0.16-0.86; P = .02).
The endpoint was driven exclusively by less TR progression in the annuloplasty group, with no TR reoperations in either group, observed Dr. Gammie. At 2 years, just 0.6% of the annuloplasty group had severe TR, compared with 5.6% of the surgery-alone group.
The rate of permanent pacemaker implantations, however, jumped from 2.5% with surgery alone to 14.1% with concomitant tricuspid annuloplasty (rate ratio, 5.75; 95% CI, 2.27-14.60). More than half of pacemakers were placed during the first 2 days after surgery.
There was no between-group difference in 2-year rates of all-cause mortality, major adverse cardiac and cerebrovascular events, readmission, quality of life, or functional status.
Less than moderate TR
In a post hoc analysis stratified by baseline TR severity, treatment failure was significantly less common with surgery plus tricuspid annuloplasty among patients with moderate TR (4.5% vs. 18.1%) but not among those with less than moderate TR and tricuspid annular dilation (3.4% vs. 6.1%).
Although the trial was not powered for the subgroup analysis, “these results call into question the idea that less than moderate TR with annular dilation should be an indication for tricuspid valve repair,” Dr. Gammie told this news organization.
“I did not repair the tricuspid valve in the setting of less than moderate TR before the trial, and my practice won’t change; but it will be based on much better evidence,” he added. “Of course, long-term data from our trial will be of great interest.”
Discussant Joseph Woo, MD, chair of surgery at Stanford (Calif.) University, congratulated the authors on a “landmark trial” that addresses a highly relevant problem without a clear-cut indication.
In the 2020 AHA/American College of Cardiology heart valve disease guideline, tricuspid valve surgery is a class I recommendation when there’s severe TR (stages C and D) and left-sided valve surgery but a class IIa recommendation in patients with progressive TR (stage B) with an annular dilation of at least 40 mm.
“The interesting findings in this study include that moderate TR was only 37% of the enrolled patients, and only 97% of the patients with degenerative MR received a mitral valve repair,” Dr. Woo said. “This level of mitral valve repair is perhaps lower than what we might expect at these centers and lower, certainly, than what the AHA/ACC guidelines recommend for surgery on asymptomatic severe mitral regurgitation.”
Panelist Roxanna Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York said, “What I was struck by is that we, as clinicians, believe that if you fix the mitral valve, maybe the tricuspid regurgitation will improve. And it seems like that is not what’s happening, and I think that’s a big takeaway.”
Session comoderator Joanna Chikwe, MD, head of cardiac surgery at Cedars-Sinai Medical Center, Los Angeles, said, “I think we can all agree that severe tricuspid regurgitation is a disaster for patients, and I think the fact the trial is designed for an additional 5 years’ follow-up will hopefully give us some insights into the clinical impact of severe tricuspid regurgitation.”
For now, “a back of the envelope calculation suggests that, for every 20 patients with moderate tricuspid regurgitation who we repair the tricuspid valve in, we would prevent severe tricuspid valve regurgitation in 1 at the price of pacemakers in 2,” she said.
Dr. Chikwe said in an interview that “transcatheter tricuspid repair is increasingly helping these patients, but if you could avoid it with a technique that doesn’t cause incremental harm beyond, perhaps, the need for pacemakers, then this is helpful data that supports that approach.”
The pacemaker burden is not negligible, she said, but also not surprising to surgeons. “If you look at national practice of mitral-tricuspid surgery, it’s about 15% after that, and it’s simply because the conduction tissue is so close to the tricuspid annulus.”
Pacemaker implantation rates, like those for concomitant tricuspid-mitral surgery, are also highly variable, and in some single-center series only around 2%, Dr. Chikwe said. “So that suggests there are technical approaches that can minimize the pacemaker rate [such as] being extremely careful to avoid suture placement around the area of the conduction tissues.”
For some the trade-off between reduced TR progression and the risk of a permanent pacemaker is worth it. “But the fact that the trial didn’t show a difference in survival, a difference in symptoms or quality of life, might suggest that patients you anticipated were high risk for surgery or didn’t have a longer projected survival aren’t going to benefit from what is quite an aggressive surgical approach,” Dr. Chikwe said.
In an accompanying editorial, Dr. Chikwe and Mario Gaudino, MD, of Weill Cornell Medicine, New York, also point out that the “very dynamic nature of tricuspid regurgitation and wide variability in assessing tricuspid annular dilatation are additional compelling reasons to leave lesser regurgitation alone.”
Julia Grapsa, MD, PhD, Kings College and tricuspid service lead at Guys and St. Thomas NHS, London, also pointed to the need for longer-term follow-up but said increased use of imaging markers is also needed to help pinpoint TR progression in these patients. “For the moment, the results should remind imagers and clinicians to refer patients earlier.”
“As a valvular heart physician, I see more and more patients coming in with significant severe tricuspid regurgitation post–mitral valve surgery and because of the time that’s passed, there’s dysfunction of the right heart, the left heart, and it’s very hard to suggest an operation because they’re at high risk,” she said. “So we’re discussing with these patients whether to do an intervention or medical management.”
“Now, with this study, and the pending longer follow-up by the authors, I’m optimistic that the class II recommendation will be class I in order to help our patients treat tricuspid regurgitation earlier than late,” said Dr. Grapsa, who is also editor-in-chief of JACC: Case Reports.
The study was funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research. Dr. Gammie reports a consultant/stockholder relationship with Edwards Lifesciences. Dr. Grapsa reports no conflicts of interest. Dr. Chikwe reports that as coprincipal investigator/study director of NCT 05051033 (an NHLBI-sponsored Cardiothoracic Surgical Trials Network trial), she collaborates with several of the study authors.
A version of this article first appeared on Medscape.com.
FROM AHA 2021