Arrhythmias & EP

Comprehensive image-based cardiovascular screening in men aged 65-74 years did not significantly reduce all-cause mortality in a new Danish study, although there were strong suggestions of benefit in some cardiovascular endpoints in the whole group and also in mortality in those aged younger than 70.

The DANCAVAS study was presented at the annual congress of the European Society of Cardiology, being held in Barcelona. It was also simultaneously published online in The New England Journal of Medicine.

“I do believe there is something in this study,” lead investigator Axel Diederichsen, PhD, Odense University Hospital, Denmark, told this news organization.

“We can decrease all-cause mortality by screening in men younger than 70. That’s amazing, I think. And in the entire group the composite endpoint of all-cause mortality/MI/stroke was significantly reduced by 7%.”

He pointed out that only 63% of the screening group actually attended the tests. “So that 63% had to account for the difference of 100% of the screening group, with an all-cause mortality endpoint. That is very ambitious. But even so, we were very close to meeting the all-cause mortality primary endpoint.”

Dr. Diederichsen believes the data could support such cardiovascular screening in men younger than 70. “In Denmark, I think this would be feasible, and our study suggests it would be cost effective compared to cancer screening,” he said.

Noting that Denmark has a relatively healthy population with good routine care, he added: “In other countries where it can be more difficult to access care or where cardiovascular health is not so good, such a screening program would probably have a greater effect.”

The population-based DANCAVAS trial randomly assigned 46,611 Danish men aged 65-74 years in a 1:2 ratio to undergo screening (invited group) or not to undergo screening (control group) for subclinical cardiovascular disease.

Screening included non-contrast electrocardiography-gated CT to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation; ankle–brachial blood-pressure measurements to detect peripheral artery disease and hypertension; and a blood sample to detect diabetes and hypercholesterolemia. Of the 16,736 men who were invited to the screening group, 10,471 (62.6%) actually attended for the screening.

In intention-to-treat analyses, after a median follow-up of 5.6 years, the primary endpoint (all cause death) had occurred in 2,106 men (12.6%) in the invited group and 3,915 men (13.1%) in the control group (hazard ratio, 0.95; 95% confidence interval, 0.90-1.00; P = .06).

The hazard ratio for stroke in the invited group, compared with the control group, was 0.93 (95% confidence interval, 0.86-0.99); for MI, 0.91 (95% CI, 0.81-1.03); for aortic dissection, 0.95 (95% CI, 0.61-1.49); and for aortic rupture, 0.81 (95% CI, 0.49-1.35).

The post-hoc composite endpoint of all-cause mortality/stroke/MI was reduced by 7%, with a hazard ratio of 0.93 (95% CI, 0.89-0.97).

There were no significant between-group differences in safety outcomes.

Subgroup analysis showed that the primary outcome of all-cause mortality was significantly reduced in men invited to screening who were aged 65-69 years (HR, 0.89; 95% CI, 0.83-0.96), with no effect in men aged 70-74.

Other findings showed that in the group invited to screening, there was a large increase in use of antiplatelet medication (HR, 3.12) and in lipid lowering agents (HR, 2.54) but no difference in use of anticoagulants, antihypertensives, and diabetes drugs or in coronary or aortic revascularization.  

In terms of cost-effectiveness, the total additional health care costs were €207 ($206 U.S.) per person in the invited group, which included the screening, medication, and all physician and hospital visits.

The quality-adjusted life-year (QALY) gained per person was 0.023, with an incremental cost-effectiveness ratio of €9,075 ($9,043) per QALY in the whole cohort and €3,860 ($3,846) in the men aged 65-69.

Dr. Diederichsen said these figures compared favorably to cancer screening, with breast cancer screening having a cost-effectiveness ratio of €22,000 ($21,923) per QALY.

“This study is a step in the right direction,” Dr. Diederichsen said in an interview. But governments will have to decide if they want to spend public money on this type of screening. I would like this to happen. We can make a case for it with this data.”

He said the study had also collected some data on younger men – aged 60-64 – and in a small group of women, which has not been analyzed yet. “We would like to look at this to help us formulate recommendations,” he added.
 

Increased medical therapy

Designated discussant of the study at the ESC session, Harriette Van Spall, MD, McMaster University, Hamilton, Ont., congratulated the DANCAVAS investigators for the trial, which she said was “implemented perfectly.”

“This is the kind of trial that is very difficult to run but comes from a big body of research from this remarkable group,” she commented.

Dr. Van Spall pointed out that it looked likely that any benefits from the screening approach were brought about by increased use of medical therapy alone (antiplatelet and lipid-lowering drugs). She added that the lack of an active screening comparator group made it unclear whether full CT imaging is more effective than active screening for traditional risk factors or assessment of global cardiovascular risk scores, and there was a missed opportunity to screen for and treat cigarette smoking in the intervention group.

“Aspects of the screening such as a full CT could be considered resource-intensive and not feasible in some health care systems. A strength of restricting the abdominal aorta iliac screening to a risk-enriched group – perhaps cigarette smokers – could have conserved additional resources,” she suggested.

Because 37% of the invited group did not attend for screening and at baseline these non-attendees had more comorbidities, this may have caused a bias in the intention to treat analysis toward the control group, thus underestimating the benefit of screening. There is therefore a role for a secondary on-treatment analysis, she noted.

Dr. Van Spall also pointed out that because of the population involved in this study, inferences can only be made to Danish men aged 65-74. 

Noting that cardiovascular disease is relevant to everyone, accounting for 24% of deaths in Danish females and 25% of deaths in Danish males, she asked the investigators to consider eliminating sex-based eligibility criteria in their next big cardiovascular prevention trial.

Susanna Price, MD, Royal Brompton Hospital, London, and cochair of the ESC session at which DANCAVAS was presented, described the study as “really interesting” and useful in planning future screening approaches.

“Although the primary endpoint was neutral, and so the results may not change practice at this time, it should promote a look at different predefined endpoints in a larger population, including both men and women, to see what the best screening interventions would be,” she commented.

“What is interesting is that we are seeing huge amounts of money being spent on acute cardiac patients after having an event, but here we are beginning to shift the focus on how to prevent cardiovascular morbidity and mortality. That is starting to be the trend in cardiovascular medicine.”

Also commenting for this news organization, Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, said: “This study is asking the important question of whether comprehensive cardiovascular screening is needed, but I don’t think it has fully given the answer, although there did appear to be some benefit in those under 70.”

Dr. Itchhaporia questioned whether the 5-year follow up was long enough to show the true benefit of screening, and she suggested that a different approach with a longer monitoring period may have been better to detect AFib.

The DANCAVAS study was supported by the Southern Region of Denmark, the Danish Heart Foundation, and the Danish Independent Research Councils.

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

Comprehensive image-based cardiovascular screening in men aged 65-74 years did not significantly reduce all-cause mortality in a new Danish study, although there were strong suggestions of benefit in some cardiovascular endpoints in the whole group and also in mortality in those aged younger than 70.

The DANCAVAS study was presented at the annual congress of the European Society of Cardiology, being held in Barcelona. It was also simultaneously published online in The New England Journal of Medicine.

“I do believe there is something in this study,” lead investigator Axel Diederichsen, PhD, Odense University Hospital, Denmark, told this news organization.

“We can decrease all-cause mortality by screening in men younger than 70. That’s amazing, I think. And in the entire group the composite endpoint of all-cause mortality/MI/stroke was significantly reduced by 7%.”

He pointed out that only 63% of the screening group actually attended the tests. “So that 63% had to account for the difference of 100% of the screening group, with an all-cause mortality endpoint. That is very ambitious. But even so, we were very close to meeting the all-cause mortality primary endpoint.”

Dr. Diederichsen believes the data could support such cardiovascular screening in men younger than 70. “In Denmark, I think this would be feasible, and our study suggests it would be cost effective compared to cancer screening,” he said.

Noting that Denmark has a relatively healthy population with good routine care, he added: “In other countries where it can be more difficult to access care or where cardiovascular health is not so good, such a screening program would probably have a greater effect.”

The population-based DANCAVAS trial randomly assigned 46,611 Danish men aged 65-74 years in a 1:2 ratio to undergo screening (invited group) or not to undergo screening (control group) for subclinical cardiovascular disease.

Screening included non-contrast electrocardiography-gated CT to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation; ankle–brachial blood-pressure measurements to detect peripheral artery disease and hypertension; and a blood sample to detect diabetes and hypercholesterolemia. Of the 16,736 men who were invited to the screening group, 10,471 (62.6%) actually attended for the screening.

In intention-to-treat analyses, after a median follow-up of 5.6 years, the primary endpoint (all cause death) had occurred in 2,106 men (12.6%) in the invited group and 3,915 men (13.1%) in the control group (hazard ratio, 0.95; 95% confidence interval, 0.90-1.00; P = .06).

The hazard ratio for stroke in the invited group, compared with the control group, was 0.93 (95% confidence interval, 0.86-0.99); for MI, 0.91 (95% CI, 0.81-1.03); for aortic dissection, 0.95 (95% CI, 0.61-1.49); and for aortic rupture, 0.81 (95% CI, 0.49-1.35).

The post-hoc composite endpoint of all-cause mortality/stroke/MI was reduced by 7%, with a hazard ratio of 0.93 (95% CI, 0.89-0.97).

There were no significant between-group differences in safety outcomes.

Subgroup analysis showed that the primary outcome of all-cause mortality was significantly reduced in men invited to screening who were aged 65-69 years (HR, 0.89; 95% CI, 0.83-0.96), with no effect in men aged 70-74.

Other findings showed that in the group invited to screening, there was a large increase in use of antiplatelet medication (HR, 3.12) and in lipid lowering agents (HR, 2.54) but no difference in use of anticoagulants, antihypertensives, and diabetes drugs or in coronary or aortic revascularization.  

In terms of cost-effectiveness, the total additional health care costs were €207 ($206 U.S.) per person in the invited group, which included the screening, medication, and all physician and hospital visits.

The quality-adjusted life-year (QALY) gained per person was 0.023, with an incremental cost-effectiveness ratio of €9,075 ($9,043) per QALY in the whole cohort and €3,860 ($3,846) in the men aged 65-69.

Dr. Diederichsen said these figures compared favorably to cancer screening, with breast cancer screening having a cost-effectiveness ratio of €22,000 ($21,923) per QALY.

“This study is a step in the right direction,” Dr. Diederichsen said in an interview. But governments will have to decide if they want to spend public money on this type of screening. I would like this to happen. We can make a case for it with this data.”

He said the study had also collected some data on younger men – aged 60-64 – and in a small group of women, which has not been analyzed yet. “We would like to look at this to help us formulate recommendations,” he added.
 

Increased medical therapy

Designated discussant of the study at the ESC session, Harriette Van Spall, MD, McMaster University, Hamilton, Ont., congratulated the DANCAVAS investigators for the trial, which she said was “implemented perfectly.”

“This is the kind of trial that is very difficult to run but comes from a big body of research from this remarkable group,” she commented.

Dr. Van Spall pointed out that it looked likely that any benefits from the screening approach were brought about by increased use of medical therapy alone (antiplatelet and lipid-lowering drugs). She added that the lack of an active screening comparator group made it unclear whether full CT imaging is more effective than active screening for traditional risk factors or assessment of global cardiovascular risk scores, and there was a missed opportunity to screen for and treat cigarette smoking in the intervention group.

“Aspects of the screening such as a full CT could be considered resource-intensive and not feasible in some health care systems. A strength of restricting the abdominal aorta iliac screening to a risk-enriched group – perhaps cigarette smokers – could have conserved additional resources,” she suggested.

Because 37% of the invited group did not attend for screening and at baseline these non-attendees had more comorbidities, this may have caused a bias in the intention to treat analysis toward the control group, thus underestimating the benefit of screening. There is therefore a role for a secondary on-treatment analysis, she noted.

Dr. Van Spall also pointed out that because of the population involved in this study, inferences can only be made to Danish men aged 65-74. 

Noting that cardiovascular disease is relevant to everyone, accounting for 24% of deaths in Danish females and 25% of deaths in Danish males, she asked the investigators to consider eliminating sex-based eligibility criteria in their next big cardiovascular prevention trial.

Susanna Price, MD, Royal Brompton Hospital, London, and cochair of the ESC session at which DANCAVAS was presented, described the study as “really interesting” and useful in planning future screening approaches.

“Although the primary endpoint was neutral, and so the results may not change practice at this time, it should promote a look at different predefined endpoints in a larger population, including both men and women, to see what the best screening interventions would be,” she commented.

“What is interesting is that we are seeing huge amounts of money being spent on acute cardiac patients after having an event, but here we are beginning to shift the focus on how to prevent cardiovascular morbidity and mortality. That is starting to be the trend in cardiovascular medicine.”

Also commenting for this news organization, Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, said: “This study is asking the important question of whether comprehensive cardiovascular screening is needed, but I don’t think it has fully given the answer, although there did appear to be some benefit in those under 70.”

Dr. Itchhaporia questioned whether the 5-year follow up was long enough to show the true benefit of screening, and she suggested that a different approach with a longer monitoring period may have been better to detect AFib.

The DANCAVAS study was supported by the Southern Region of Denmark, the Danish Heart Foundation, and the Danish Independent Research Councils.

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

Comprehensive image-based cardiovascular screening in men aged 65-74 years did not significantly reduce all-cause mortality in a new Danish study, although there were strong suggestions of benefit in some cardiovascular endpoints in the whole group and also in mortality in those aged younger than 70.

The DANCAVAS study was presented at the annual congress of the European Society of Cardiology, being held in Barcelona. It was also simultaneously published online in The New England Journal of Medicine.

“I do believe there is something in this study,” lead investigator Axel Diederichsen, PhD, Odense University Hospital, Denmark, told this news organization.

“We can decrease all-cause mortality by screening in men younger than 70. That’s amazing, I think. And in the entire group the composite endpoint of all-cause mortality/MI/stroke was significantly reduced by 7%.”

He pointed out that only 63% of the screening group actually attended the tests. “So that 63% had to account for the difference of 100% of the screening group, with an all-cause mortality endpoint. That is very ambitious. But even so, we were very close to meeting the all-cause mortality primary endpoint.”

Dr. Diederichsen believes the data could support such cardiovascular screening in men younger than 70. “In Denmark, I think this would be feasible, and our study suggests it would be cost effective compared to cancer screening,” he said.

Noting that Denmark has a relatively healthy population with good routine care, he added: “In other countries where it can be more difficult to access care or where cardiovascular health is not so good, such a screening program would probably have a greater effect.”

The population-based DANCAVAS trial randomly assigned 46,611 Danish men aged 65-74 years in a 1:2 ratio to undergo screening (invited group) or not to undergo screening (control group) for subclinical cardiovascular disease.

Screening included non-contrast electrocardiography-gated CT to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation; ankle–brachial blood-pressure measurements to detect peripheral artery disease and hypertension; and a blood sample to detect diabetes and hypercholesterolemia. Of the 16,736 men who were invited to the screening group, 10,471 (62.6%) actually attended for the screening.

In intention-to-treat analyses, after a median follow-up of 5.6 years, the primary endpoint (all cause death) had occurred in 2,106 men (12.6%) in the invited group and 3,915 men (13.1%) in the control group (hazard ratio, 0.95; 95% confidence interval, 0.90-1.00; P = .06).

The hazard ratio for stroke in the invited group, compared with the control group, was 0.93 (95% confidence interval, 0.86-0.99); for MI, 0.91 (95% CI, 0.81-1.03); for aortic dissection, 0.95 (95% CI, 0.61-1.49); and for aortic rupture, 0.81 (95% CI, 0.49-1.35).

The post-hoc composite endpoint of all-cause mortality/stroke/MI was reduced by 7%, with a hazard ratio of 0.93 (95% CI, 0.89-0.97).

There were no significant between-group differences in safety outcomes.

Subgroup analysis showed that the primary outcome of all-cause mortality was significantly reduced in men invited to screening who were aged 65-69 years (HR, 0.89; 95% CI, 0.83-0.96), with no effect in men aged 70-74.

Other findings showed that in the group invited to screening, there was a large increase in use of antiplatelet medication (HR, 3.12) and in lipid lowering agents (HR, 2.54) but no difference in use of anticoagulants, antihypertensives, and diabetes drugs or in coronary or aortic revascularization.  

In terms of cost-effectiveness, the total additional health care costs were €207 ($206 U.S.) per person in the invited group, which included the screening, medication, and all physician and hospital visits.

The quality-adjusted life-year (QALY) gained per person was 0.023, with an incremental cost-effectiveness ratio of €9,075 ($9,043) per QALY in the whole cohort and €3,860 ($3,846) in the men aged 65-69.

Dr. Diederichsen said these figures compared favorably to cancer screening, with breast cancer screening having a cost-effectiveness ratio of €22,000 ($21,923) per QALY.

“This study is a step in the right direction,” Dr. Diederichsen said in an interview. But governments will have to decide if they want to spend public money on this type of screening. I would like this to happen. We can make a case for it with this data.”

He said the study had also collected some data on younger men – aged 60-64 – and in a small group of women, which has not been analyzed yet. “We would like to look at this to help us formulate recommendations,” he added.
 

Increased medical therapy

Designated discussant of the study at the ESC session, Harriette Van Spall, MD, McMaster University, Hamilton, Ont., congratulated the DANCAVAS investigators for the trial, which she said was “implemented perfectly.”

“This is the kind of trial that is very difficult to run but comes from a big body of research from this remarkable group,” she commented.

Dr. Van Spall pointed out that it looked likely that any benefits from the screening approach were brought about by increased use of medical therapy alone (antiplatelet and lipid-lowering drugs). She added that the lack of an active screening comparator group made it unclear whether full CT imaging is more effective than active screening for traditional risk factors or assessment of global cardiovascular risk scores, and there was a missed opportunity to screen for and treat cigarette smoking in the intervention group.

“Aspects of the screening such as a full CT could be considered resource-intensive and not feasible in some health care systems. A strength of restricting the abdominal aorta iliac screening to a risk-enriched group – perhaps cigarette smokers – could have conserved additional resources,” she suggested.

Because 37% of the invited group did not attend for screening and at baseline these non-attendees had more comorbidities, this may have caused a bias in the intention to treat analysis toward the control group, thus underestimating the benefit of screening. There is therefore a role for a secondary on-treatment analysis, she noted.

Dr. Van Spall also pointed out that because of the population involved in this study, inferences can only be made to Danish men aged 65-74. 

Noting that cardiovascular disease is relevant to everyone, accounting for 24% of deaths in Danish females and 25% of deaths in Danish males, she asked the investigators to consider eliminating sex-based eligibility criteria in their next big cardiovascular prevention trial.

Susanna Price, MD, Royal Brompton Hospital, London, and cochair of the ESC session at which DANCAVAS was presented, described the study as “really interesting” and useful in planning future screening approaches.

“Although the primary endpoint was neutral, and so the results may not change practice at this time, it should promote a look at different predefined endpoints in a larger population, including both men and women, to see what the best screening interventions would be,” she commented.

“What is interesting is that we are seeing huge amounts of money being spent on acute cardiac patients after having an event, but here we are beginning to shift the focus on how to prevent cardiovascular morbidity and mortality. That is starting to be the trend in cardiovascular medicine.”

Also commenting for this news organization, Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, said: “This study is asking the important question of whether comprehensive cardiovascular screening is needed, but I don’t think it has fully given the answer, although there did appear to be some benefit in those under 70.”

Dr. Itchhaporia questioned whether the 5-year follow up was long enough to show the true benefit of screening, and she suggested that a different approach with a longer monitoring period may have been better to detect AFib.

The DANCAVAS study was supported by the Southern Region of Denmark, the Danish Heart Foundation, and the Danish Independent Research Councils.

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

Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.

The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.

There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.

Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.

“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”

The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.

Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.

This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.

“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.

Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”

Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.

In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”

The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”

Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.

Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.

Detailed results

Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.

The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.

During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.

LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.

With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.

Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.

Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
 

‘Modest’ degree of CAD?

An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.

“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.

He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”

Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.

He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.

The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”

George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.

Copyright American Heart Association copyright American Heart Association copyright American Heart Association

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

Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.

The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.

There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.

Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.

“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”

The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.

Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.

This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.

“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.

Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”

Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.

In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”

The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”

Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.

Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.

Detailed results

Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.

The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.

During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.

LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.

With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.

Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.

Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
 

‘Modest’ degree of CAD?

An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.

“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.

He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”

Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.

He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.

The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”

George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.

Copyright American Heart Association copyright American Heart Association copyright American Heart Association

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

Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.

The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.

There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.

Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.

“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”

The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.

Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.

This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.

“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.

Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”

Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.

In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”

The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”

Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.

Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.

Detailed results

Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.

The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.

During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.

LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.

With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.

Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.

Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
 

‘Modest’ degree of CAD?

An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.

“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.

He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”

Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.

He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.

The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”

George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.

Copyright American Heart Association copyright American Heart Association copyright American Heart Association

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

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

A decades-old drug, added to standard loop diuretics, could potentially help more volume-overloaded patients with acute decompensated heart failure (ADHF) to be discharged from the hospital ‘dry,’ a randomized trial suggests.

Those who received intravenous acetazolamide, compared with placebo, on top of a usual-care IV loop diuretic in the multicenter study were 46% more likely to achieve “successful” decongestion – that is, to leave the hospital without lingering signs of volume overload.

The trial, with more than 500 patients, is the first “to unequivocally show benefit of any drug, namely acetazolamide, on major heart failure outcomes in patients with acute decompensated heart failure,” said Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, at a media briefing during the annual congress of the European Society of Cardiology, Barcelona.

The patients who received acetazolamide “also had a shorter hospital stay, having a major impact on not only quality of life, but also health care expenditures,” said Dr. Mullens, who leads the steering committee of the trial conducted in Belgium. He presented the results of Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) at ESC 2022 and is lead author on its same-day publication in the New England Journal of Medicine.
 

Complementary effects?

Current guidelines on managing volume-overloaded patients with ADHF owe a lot to the 2011 DOSE trial, which provided some of the first randomized-trial evidence in an arena led largely by clinical tradition. The advantages it saw with the high-dose furosemide strategy helped it enter into clinical practice, but even in DOSE, the strategy fell short of achieving full decongestion for many patients.

The ADVOR report describes acetazolamide as a carbonic anhydrase inhibitor that reduces sodium recovery in the proximal tubule, similar to the function of loop diuretics in the loop of Henle. Acting in different segments of the nephron, acetazolamide and loop diuretics like furosemide may potentially have complementary effects that improve diuretic “efficiency.”

The difference in decongestion effect between the acetazolamide and placebo groups grew consistently from baseline to day 3. “There was an increase in treatment effect over consecutive days,” Dr. Mullens said. “This highlights the importance of treating congestion both early and aggressively. You cannot catch up,” he said. “If you don’t treat them aggressively initially, you can never get them dry.”

Of the trial’s 519 patients, 42.2% of those assigned to acetazolamide and 30.5% of those in the control group were judged to have had successful decongestion at 3 days, the primary endpoint. Successful decongestion meant they had no remaining signs of volume overload, such as edema, pleural effusion, or ascites.

Although the trial wasn’t powered for clinical outcomes, the 3-month rates of death from any cause or rehospitalization for heart failure were similar at 29.7% in the acetazolamide group and 27.8% for the control group. All-cause mortality in an exploratory analysis was also statistically comparable at 15.2% and 12%, respectively.
 

Decongestion and clinical outcomes

The study is noteworthy “because it tests a readily available diuretic, acetazolamide, that is not used widely for ADHF,” and showed a benefit at 3 days from adding the drug to a prescribed loop diuretic regimen, Mark H. Drazner, MD, University of Texas Southwestern Medical Center, Dallas, told this news organization.

The benefit didn’t translate into improved clinical outcomes; indeed, mortality at 3 months was numerically higher in the acetazolamide group, observed Dr. Drazner, who is unaffiliated with the study.

Although ADVOR isn’t powered for mortality, he acknowledged, “one would expect the enhanced decongestion would have led to improved outcomes,” or at least a signal of such improvement.

It’s worth noting, Dr. Drazner added, “that the strategy tested was to add acetazolamide up front, on day 1, before loop diuretics were maximized.”

Indeed, the published report says all patients received IV loop diuretics at double the oral maintenance dose, given the first day in a single bolus immediately on randomization. The dose was split into two doses, given at least 6 hours apart, on day 2 and day 3. “The bolus of acetazolamide or matching placebo was administered simultaneously with the first dose of loop diuretics each day,” it states.

Although the protocol called for one loop diuretic dose on day 1, typically in practice patients would be dosed twice or three times each day, Dr. Drazner observed. Once-daily IV diuretic dosing may be less effective than a 2- or 3-times-per-day schedule, he said. As a result, acetazolamide might achieve faster decongestion after it is added to the loop diuretic, a benefit that would not otherwise be available in practice.
 

Messages for practice

Before this trial, Dr. Drazner said, he would usually add the thiazide diuretic metolazone as needed “to augment diuresis beyond maximum loop diuretics.” After ADVOR, “I’d be willing to try acetazolamide in that setting, recognizing I also don’t know the impact of metolazone on outcomes.”

Still, he would restrict either drug to patients who fail on maximal loop diuretics “rather than adding it routinely and up front, before the loop diuretics are maximized.”

More data are needed, Dr. Drazner said, including from a larger clinical-outcomes trial to confirm the strategy’s safety, before “the up-front addition of acetazolamide to submaximal loop diuretics doses” could become part of standard practice in ADHF.

Given the data so far, including those from ADVOR, “treatment with loop diuretics alone is probably sufficient for successful decongestion” among patients likely to respond to the drugs: that is, “those who are younger, those who have less severe or new-onset heart failure, and those who have normal kidney function,” states an editorial accompanying the published report.

“However, for the large group of patients who have some degree of diuretic resistance, or for those who have an inadequate initial response to loop-diuretic therapy, these data suggest the use of acetazolamide as a reasonable adjunct to achieving more rapid decongestion,” writes G. Michael Felker, MD, Duke University School of Medicine, Durham, N.C. Dr. Felker was lead author on the DOSE primary publication.

ADVOR entered volume-overloaded patients with ADHF and elevated natriuretic peptide levels who had been on oral maintenance with at least 40 mg of furosemide, or equivalent doses of other loop diuretics, for at least a month before randomization.

They were assigned to either IV acetazolamide at 500 mg once daily (n = 259) or placebo (n = 260) on top of an IV loop diuretic, at 27 centers in Belgium.

The risk ratio for the primary endpoint, successful decongestion after 3 days, was 1.46 (95% confidence interval, 1.17-1.82, P < .001) for the acetazolamide versus placebo groups.

In exploratory analyses, acetazolamide versus placebo, the RR for successful decongestion among patients who survived to discharge was increased at 1.27 (95% CI, 1.13-1.43). The hazard ratio for death from any cause at 3 months was not significant at 1.28 (95% CI, 0.78-2.05), nor was the HR for heart-failure rehospitalization at 3 months, 1.07 (95% CI, 0.71-1.59).

The role of SGLT2 inhibitors

ADVOR, understandably but maybe problematically, excluded patients taking SGLT2 inhibitors. The drugs have diuretic effects, among other useful properties, and became core therapy for a range of heart failure types after the trial was designed.

“This exclusion presents a conundrum for applying these results in contemporary clinical care,” Dr. Felker writes. For example, “the data supporting the efficacy and safety of SGLT2 inhibitors across the broad spectrum of patients with heart failure are now overwhelming, and most patients who are hospitalized for heart failure have a clear indication for these agents.”

Given that no ADVOR patients were on the drugs, his editorial states, “we can only speculate as to the efficacy of acetazolamide in patients treated with background SGLT2 inhibitors, which could potentially be additive, subadditive, or synergistic.”

The SGLT2 inhibitors will likely “be used in ADHF in the future, based on studies such as EMPULSE. It will be important to know whether SGLT2 inhibitors change the risk-benefit of also giving acetazolamide,” Dr. Drazner said when interviewed.

“I don’t think there’s any safety issue with regards to the combination of SGLT2 inhibitors and acetazolamide,” Dr. Mullens said. Their diuretic effects are likely to be additive, he proposed.

“Although SGLT2 inhibitors and acetazolamide both exert natriuretic and diuretic effects on the proximal tubules, their mode of action and potency differ substantially,” the published report states.

ADVOR is funded by the Belgian Health Care Knowledge Center. Dr. Mullens discloses receiving fees for speaking from Abbott Fund, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Medtronic, and Novartis. Disclosures for the other authors are at NEJM.org. Dr. Drazner has reported no relevant financial relationships. Dr. Felker discloses serving as a consultant for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cardionomic, Cytokinetics, Novartis, Reprieve, and Sequana.

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

A decades-old drug, added to standard loop diuretics, could potentially help more volume-overloaded patients with acute decompensated heart failure (ADHF) to be discharged from the hospital ‘dry,’ a randomized trial suggests.

Those who received intravenous acetazolamide, compared with placebo, on top of a usual-care IV loop diuretic in the multicenter study were 46% more likely to achieve “successful” decongestion – that is, to leave the hospital without lingering signs of volume overload.

The trial, with more than 500 patients, is the first “to unequivocally show benefit of any drug, namely acetazolamide, on major heart failure outcomes in patients with acute decompensated heart failure,” said Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, at a media briefing during the annual congress of the European Society of Cardiology, Barcelona.

The patients who received acetazolamide “also had a shorter hospital stay, having a major impact on not only quality of life, but also health care expenditures,” said Dr. Mullens, who leads the steering committee of the trial conducted in Belgium. He presented the results of Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) at ESC 2022 and is lead author on its same-day publication in the New England Journal of Medicine.
 

Complementary effects?

Current guidelines on managing volume-overloaded patients with ADHF owe a lot to the 2011 DOSE trial, which provided some of the first randomized-trial evidence in an arena led largely by clinical tradition. The advantages it saw with the high-dose furosemide strategy helped it enter into clinical practice, but even in DOSE, the strategy fell short of achieving full decongestion for many patients.

The ADVOR report describes acetazolamide as a carbonic anhydrase inhibitor that reduces sodium recovery in the proximal tubule, similar to the function of loop diuretics in the loop of Henle. Acting in different segments of the nephron, acetazolamide and loop diuretics like furosemide may potentially have complementary effects that improve diuretic “efficiency.”

The difference in decongestion effect between the acetazolamide and placebo groups grew consistently from baseline to day 3. “There was an increase in treatment effect over consecutive days,” Dr. Mullens said. “This highlights the importance of treating congestion both early and aggressively. You cannot catch up,” he said. “If you don’t treat them aggressively initially, you can never get them dry.”

Of the trial’s 519 patients, 42.2% of those assigned to acetazolamide and 30.5% of those in the control group were judged to have had successful decongestion at 3 days, the primary endpoint. Successful decongestion meant they had no remaining signs of volume overload, such as edema, pleural effusion, or ascites.

Although the trial wasn’t powered for clinical outcomes, the 3-month rates of death from any cause or rehospitalization for heart failure were similar at 29.7% in the acetazolamide group and 27.8% for the control group. All-cause mortality in an exploratory analysis was also statistically comparable at 15.2% and 12%, respectively.
 

Decongestion and clinical outcomes

The study is noteworthy “because it tests a readily available diuretic, acetazolamide, that is not used widely for ADHF,” and showed a benefit at 3 days from adding the drug to a prescribed loop diuretic regimen, Mark H. Drazner, MD, University of Texas Southwestern Medical Center, Dallas, told this news organization.

The benefit didn’t translate into improved clinical outcomes; indeed, mortality at 3 months was numerically higher in the acetazolamide group, observed Dr. Drazner, who is unaffiliated with the study.

Although ADVOR isn’t powered for mortality, he acknowledged, “one would expect the enhanced decongestion would have led to improved outcomes,” or at least a signal of such improvement.

It’s worth noting, Dr. Drazner added, “that the strategy tested was to add acetazolamide up front, on day 1, before loop diuretics were maximized.”

Indeed, the published report says all patients received IV loop diuretics at double the oral maintenance dose, given the first day in a single bolus immediately on randomization. The dose was split into two doses, given at least 6 hours apart, on day 2 and day 3. “The bolus of acetazolamide or matching placebo was administered simultaneously with the first dose of loop diuretics each day,” it states.

Although the protocol called for one loop diuretic dose on day 1, typically in practice patients would be dosed twice or three times each day, Dr. Drazner observed. Once-daily IV diuretic dosing may be less effective than a 2- or 3-times-per-day schedule, he said. As a result, acetazolamide might achieve faster decongestion after it is added to the loop diuretic, a benefit that would not otherwise be available in practice.
 

Messages for practice

Before this trial, Dr. Drazner said, he would usually add the thiazide diuretic metolazone as needed “to augment diuresis beyond maximum loop diuretics.” After ADVOR, “I’d be willing to try acetazolamide in that setting, recognizing I also don’t know the impact of metolazone on outcomes.”

Still, he would restrict either drug to patients who fail on maximal loop diuretics “rather than adding it routinely and up front, before the loop diuretics are maximized.”

More data are needed, Dr. Drazner said, including from a larger clinical-outcomes trial to confirm the strategy’s safety, before “the up-front addition of acetazolamide to submaximal loop diuretics doses” could become part of standard practice in ADHF.

Given the data so far, including those from ADVOR, “treatment with loop diuretics alone is probably sufficient for successful decongestion” among patients likely to respond to the drugs: that is, “those who are younger, those who have less severe or new-onset heart failure, and those who have normal kidney function,” states an editorial accompanying the published report.

“However, for the large group of patients who have some degree of diuretic resistance, or for those who have an inadequate initial response to loop-diuretic therapy, these data suggest the use of acetazolamide as a reasonable adjunct to achieving more rapid decongestion,” writes G. Michael Felker, MD, Duke University School of Medicine, Durham, N.C. Dr. Felker was lead author on the DOSE primary publication.

ADVOR entered volume-overloaded patients with ADHF and elevated natriuretic peptide levels who had been on oral maintenance with at least 40 mg of furosemide, or equivalent doses of other loop diuretics, for at least a month before randomization.

They were assigned to either IV acetazolamide at 500 mg once daily (n = 259) or placebo (n = 260) on top of an IV loop diuretic, at 27 centers in Belgium.

The risk ratio for the primary endpoint, successful decongestion after 3 days, was 1.46 (95% confidence interval, 1.17-1.82, P < .001) for the acetazolamide versus placebo groups.

In exploratory analyses, acetazolamide versus placebo, the RR for successful decongestion among patients who survived to discharge was increased at 1.27 (95% CI, 1.13-1.43). The hazard ratio for death from any cause at 3 months was not significant at 1.28 (95% CI, 0.78-2.05), nor was the HR for heart-failure rehospitalization at 3 months, 1.07 (95% CI, 0.71-1.59).

The role of SGLT2 inhibitors

ADVOR, understandably but maybe problematically, excluded patients taking SGLT2 inhibitors. The drugs have diuretic effects, among other useful properties, and became core therapy for a range of heart failure types after the trial was designed.

“This exclusion presents a conundrum for applying these results in contemporary clinical care,” Dr. Felker writes. For example, “the data supporting the efficacy and safety of SGLT2 inhibitors across the broad spectrum of patients with heart failure are now overwhelming, and most patients who are hospitalized for heart failure have a clear indication for these agents.”

Given that no ADVOR patients were on the drugs, his editorial states, “we can only speculate as to the efficacy of acetazolamide in patients treated with background SGLT2 inhibitors, which could potentially be additive, subadditive, or synergistic.”

The SGLT2 inhibitors will likely “be used in ADHF in the future, based on studies such as EMPULSE. It will be important to know whether SGLT2 inhibitors change the risk-benefit of also giving acetazolamide,” Dr. Drazner said when interviewed.

“I don’t think there’s any safety issue with regards to the combination of SGLT2 inhibitors and acetazolamide,” Dr. Mullens said. Their diuretic effects are likely to be additive, he proposed.

“Although SGLT2 inhibitors and acetazolamide both exert natriuretic and diuretic effects on the proximal tubules, their mode of action and potency differ substantially,” the published report states.

ADVOR is funded by the Belgian Health Care Knowledge Center. Dr. Mullens discloses receiving fees for speaking from Abbott Fund, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Medtronic, and Novartis. Disclosures for the other authors are at NEJM.org. Dr. Drazner has reported no relevant financial relationships. Dr. Felker discloses serving as a consultant for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cardionomic, Cytokinetics, Novartis, Reprieve, and Sequana.

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

A decades-old drug, added to standard loop diuretics, could potentially help more volume-overloaded patients with acute decompensated heart failure (ADHF) to be discharged from the hospital ‘dry,’ a randomized trial suggests.

Those who received intravenous acetazolamide, compared with placebo, on top of a usual-care IV loop diuretic in the multicenter study were 46% more likely to achieve “successful” decongestion – that is, to leave the hospital without lingering signs of volume overload.

The trial, with more than 500 patients, is the first “to unequivocally show benefit of any drug, namely acetazolamide, on major heart failure outcomes in patients with acute decompensated heart failure,” said Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, at a media briefing during the annual congress of the European Society of Cardiology, Barcelona.

The patients who received acetazolamide “also had a shorter hospital stay, having a major impact on not only quality of life, but also health care expenditures,” said Dr. Mullens, who leads the steering committee of the trial conducted in Belgium. He presented the results of Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) at ESC 2022 and is lead author on its same-day publication in the New England Journal of Medicine.
 

Complementary effects?

Current guidelines on managing volume-overloaded patients with ADHF owe a lot to the 2011 DOSE trial, which provided some of the first randomized-trial evidence in an arena led largely by clinical tradition. The advantages it saw with the high-dose furosemide strategy helped it enter into clinical practice, but even in DOSE, the strategy fell short of achieving full decongestion for many patients.

The ADVOR report describes acetazolamide as a carbonic anhydrase inhibitor that reduces sodium recovery in the proximal tubule, similar to the function of loop diuretics in the loop of Henle. Acting in different segments of the nephron, acetazolamide and loop diuretics like furosemide may potentially have complementary effects that improve diuretic “efficiency.”

The difference in decongestion effect between the acetazolamide and placebo groups grew consistently from baseline to day 3. “There was an increase in treatment effect over consecutive days,” Dr. Mullens said. “This highlights the importance of treating congestion both early and aggressively. You cannot catch up,” he said. “If you don’t treat them aggressively initially, you can never get them dry.”

Of the trial’s 519 patients, 42.2% of those assigned to acetazolamide and 30.5% of those in the control group were judged to have had successful decongestion at 3 days, the primary endpoint. Successful decongestion meant they had no remaining signs of volume overload, such as edema, pleural effusion, or ascites.

Although the trial wasn’t powered for clinical outcomes, the 3-month rates of death from any cause or rehospitalization for heart failure were similar at 29.7% in the acetazolamide group and 27.8% for the control group. All-cause mortality in an exploratory analysis was also statistically comparable at 15.2% and 12%, respectively.
 

Decongestion and clinical outcomes

The study is noteworthy “because it tests a readily available diuretic, acetazolamide, that is not used widely for ADHF,” and showed a benefit at 3 days from adding the drug to a prescribed loop diuretic regimen, Mark H. Drazner, MD, University of Texas Southwestern Medical Center, Dallas, told this news organization.

The benefit didn’t translate into improved clinical outcomes; indeed, mortality at 3 months was numerically higher in the acetazolamide group, observed Dr. Drazner, who is unaffiliated with the study.

Although ADVOR isn’t powered for mortality, he acknowledged, “one would expect the enhanced decongestion would have led to improved outcomes,” or at least a signal of such improvement.

It’s worth noting, Dr. Drazner added, “that the strategy tested was to add acetazolamide up front, on day 1, before loop diuretics were maximized.”

Indeed, the published report says all patients received IV loop diuretics at double the oral maintenance dose, given the first day in a single bolus immediately on randomization. The dose was split into two doses, given at least 6 hours apart, on day 2 and day 3. “The bolus of acetazolamide or matching placebo was administered simultaneously with the first dose of loop diuretics each day,” it states.

Although the protocol called for one loop diuretic dose on day 1, typically in practice patients would be dosed twice or three times each day, Dr. Drazner observed. Once-daily IV diuretic dosing may be less effective than a 2- or 3-times-per-day schedule, he said. As a result, acetazolamide might achieve faster decongestion after it is added to the loop diuretic, a benefit that would not otherwise be available in practice.
 

Messages for practice

Before this trial, Dr. Drazner said, he would usually add the thiazide diuretic metolazone as needed “to augment diuresis beyond maximum loop diuretics.” After ADVOR, “I’d be willing to try acetazolamide in that setting, recognizing I also don’t know the impact of metolazone on outcomes.”

Still, he would restrict either drug to patients who fail on maximal loop diuretics “rather than adding it routinely and up front, before the loop diuretics are maximized.”

More data are needed, Dr. Drazner said, including from a larger clinical-outcomes trial to confirm the strategy’s safety, before “the up-front addition of acetazolamide to submaximal loop diuretics doses” could become part of standard practice in ADHF.

Given the data so far, including those from ADVOR, “treatment with loop diuretics alone is probably sufficient for successful decongestion” among patients likely to respond to the drugs: that is, “those who are younger, those who have less severe or new-onset heart failure, and those who have normal kidney function,” states an editorial accompanying the published report.

“However, for the large group of patients who have some degree of diuretic resistance, or for those who have an inadequate initial response to loop-diuretic therapy, these data suggest the use of acetazolamide as a reasonable adjunct to achieving more rapid decongestion,” writes G. Michael Felker, MD, Duke University School of Medicine, Durham, N.C. Dr. Felker was lead author on the DOSE primary publication.

ADVOR entered volume-overloaded patients with ADHF and elevated natriuretic peptide levels who had been on oral maintenance with at least 40 mg of furosemide, or equivalent doses of other loop diuretics, for at least a month before randomization.

They were assigned to either IV acetazolamide at 500 mg once daily (n = 259) or placebo (n = 260) on top of an IV loop diuretic, at 27 centers in Belgium.

The risk ratio for the primary endpoint, successful decongestion after 3 days, was 1.46 (95% confidence interval, 1.17-1.82, P < .001) for the acetazolamide versus placebo groups.

In exploratory analyses, acetazolamide versus placebo, the RR for successful decongestion among patients who survived to discharge was increased at 1.27 (95% CI, 1.13-1.43). The hazard ratio for death from any cause at 3 months was not significant at 1.28 (95% CI, 0.78-2.05), nor was the HR for heart-failure rehospitalization at 3 months, 1.07 (95% CI, 0.71-1.59).

The role of SGLT2 inhibitors

ADVOR, understandably but maybe problematically, excluded patients taking SGLT2 inhibitors. The drugs have diuretic effects, among other useful properties, and became core therapy for a range of heart failure types after the trial was designed.

“This exclusion presents a conundrum for applying these results in contemporary clinical care,” Dr. Felker writes. For example, “the data supporting the efficacy and safety of SGLT2 inhibitors across the broad spectrum of patients with heart failure are now overwhelming, and most patients who are hospitalized for heart failure have a clear indication for these agents.”

Given that no ADVOR patients were on the drugs, his editorial states, “we can only speculate as to the efficacy of acetazolamide in patients treated with background SGLT2 inhibitors, which could potentially be additive, subadditive, or synergistic.”

The SGLT2 inhibitors will likely “be used in ADHF in the future, based on studies such as EMPULSE. It will be important to know whether SGLT2 inhibitors change the risk-benefit of also giving acetazolamide,” Dr. Drazner said when interviewed.

“I don’t think there’s any safety issue with regards to the combination of SGLT2 inhibitors and acetazolamide,” Dr. Mullens said. Their diuretic effects are likely to be additive, he proposed.

“Although SGLT2 inhibitors and acetazolamide both exert natriuretic and diuretic effects on the proximal tubules, their mode of action and potency differ substantially,” the published report states.

ADVOR is funded by the Belgian Health Care Knowledge Center. Dr. Mullens discloses receiving fees for speaking from Abbott Fund, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Medtronic, and Novartis. Disclosures for the other authors are at NEJM.org. Dr. Drazner has reported no relevant financial relationships. Dr. Felker discloses serving as a consultant for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cardionomic, Cytokinetics, Novartis, Reprieve, and Sequana.

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

Patients who received a first prescription for medicinal cannabis for chronic pain were more likely to have new onset of arrhythmia – bradyarrhythmia, tachyarrhythmia, or a conduction disorder – within 6 months than were similar nonusers, in a new case-control study.

VladK213/Getty Images

There were no between-group differences in the incidence of heart failure or acute coronary syndrome.

The researchers identified 5,071 patients in a national Danish registry who had filled at least one prescription for medicinal cannabis for chronic pain and matched each patient with five patients of the same sex, age range, and type of chronic pain who did not receive this therapy.

The relative risk for arrhythmia was 83% higher in those who used medicinal cannabis than it was in the other patients, study author Nina Nouhravesh, MD, told this news organization in an email.

However, the absolute risks for arrhythmia were slight – a 0.86% risk (95% confidence interval, 0.61%-1.1%) in medicinal cannabis users versus a 0.47% risk (95% CI, 0.38%-0.56%) in those who did not use medicinal cannabis.

“Since medical cannabis is a relatively new drug for a large market of patients with chronic pain, it is important to investigate and report serious side effects,” said Dr. Nouhravesh, from Gentofte University Hospital, Denmark.

The study results, she said, suggest that “there may be a previously unreported risk of arrhythmias following medical cannabis use.”

“Even though the absolute risk difference is small, both patients and physicians should have as much information as possible when weighing up the pros and cons of any treatment,” Dr. Nouhravesh said, adding that “the findings of this study raise concerns for both legal and illegal [cannabis] use worldwide.”

The results will be presented at the annual European Society of Cardiology (ESC) Congress 2022.
 

Too soon to tell?

However, Brian Olshansky, MD, who was not involved with this research, cautions that it is important to consider several study limitations before drawing clinical implications.

“Other data and reports have considered the possibility of arrhythmias in relationship to marijuana use, and the data go in both directions,” Dr. Olshansky, a clinical cardiac electrophysiologist and professor emeritus at University of Iowa Hospitals, Iowa City, pointed out in an email.

“Importantly, arrhythmias, by themselves, are not necessarily consequential,” he stressed. “In any case,” he added, the risks in the current study are “extraordinarily small.”

Sinus bradycardia, sinus tachycardia, and premature atrial or ventricular contractions could be totally benign, he said. On the other hand, arrhythmias may indicate the presence of atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation, which are potentially dangerous.

There may be a specific “high risk” group who can develop potentially serious arrhythmias, Dr. Olshansky suggested.

“There is no evidence that any of these patients underwent or required any treatment for their arrhythmia or that stopping or starting the cannabinoids affected the arrhythmia one way or the other,” he said. “In addition, there is no dose/arrhythmia relationship.”

More patients in the medicinal cannabis group than in the nonuser group were also taking opioids (49% vs. 30%), nonsteroidal anti-inflammatory drugs (24% vs. 19%), antiepileptics (35% vs. 23%), or tricyclic antidepressants (11% vs. 4%), he noted.

In summary, according to Dr. Olshansky, “these data pose no obvious health concern and provide no vital knowledge for physicians prescribing cannabis.”

“My concern is that the information will be overblown,” he cautioned. “If the cannabinoid actually has benefit in terms of pain reduction, its use may be mitigated based on the fear of an arrhythmia that may occur – but the risk of an arrhythmia, in any event, is very small and undefined in terms of its seriousness.”
 

Cancer, musculoskeletal, and neurologic pain

For this analysis, the researchers identified 1.8 million patients in Denmark who were diagnosed with chronic pain between 2018 and 2021.

Of those, around 5,000 patients had claimed at least one prescription of medicinal cannabis (dronabinol 29%, cannabinoids 46%, or cannabidiol 25%).

The patients had a median age of 60 years, and 63% were women.

The cannabis users had been prescribed this therapy for musculoskeletal (35%), cancer (18%), neurological (14%), or other (33%) pain, Dr. Nouhravesh said. 

The researchers and Dr. Olshansky have no relevant financial disclosures.  

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

Patients who received a first prescription for medicinal cannabis for chronic pain were more likely to have new onset of arrhythmia – bradyarrhythmia, tachyarrhythmia, or a conduction disorder – within 6 months than were similar nonusers, in a new case-control study.

VladK213/Getty Images

There were no between-group differences in the incidence of heart failure or acute coronary syndrome.

The researchers identified 5,071 patients in a national Danish registry who had filled at least one prescription for medicinal cannabis for chronic pain and matched each patient with five patients of the same sex, age range, and type of chronic pain who did not receive this therapy.

The relative risk for arrhythmia was 83% higher in those who used medicinal cannabis than it was in the other patients, study author Nina Nouhravesh, MD, told this news organization in an email.

However, the absolute risks for arrhythmia were slight – a 0.86% risk (95% confidence interval, 0.61%-1.1%) in medicinal cannabis users versus a 0.47% risk (95% CI, 0.38%-0.56%) in those who did not use medicinal cannabis.

“Since medical cannabis is a relatively new drug for a large market of patients with chronic pain, it is important to investigate and report serious side effects,” said Dr. Nouhravesh, from Gentofte University Hospital, Denmark.

The study results, she said, suggest that “there may be a previously unreported risk of arrhythmias following medical cannabis use.”

“Even though the absolute risk difference is small, both patients and physicians should have as much information as possible when weighing up the pros and cons of any treatment,” Dr. Nouhravesh said, adding that “the findings of this study raise concerns for both legal and illegal [cannabis] use worldwide.”

The results will be presented at the annual European Society of Cardiology (ESC) Congress 2022.
 

Too soon to tell?

However, Brian Olshansky, MD, who was not involved with this research, cautions that it is important to consider several study limitations before drawing clinical implications.

“Other data and reports have considered the possibility of arrhythmias in relationship to marijuana use, and the data go in both directions,” Dr. Olshansky, a clinical cardiac electrophysiologist and professor emeritus at University of Iowa Hospitals, Iowa City, pointed out in an email.

“Importantly, arrhythmias, by themselves, are not necessarily consequential,” he stressed. “In any case,” he added, the risks in the current study are “extraordinarily small.”

Sinus bradycardia, sinus tachycardia, and premature atrial or ventricular contractions could be totally benign, he said. On the other hand, arrhythmias may indicate the presence of atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation, which are potentially dangerous.

There may be a specific “high risk” group who can develop potentially serious arrhythmias, Dr. Olshansky suggested.

“There is no evidence that any of these patients underwent or required any treatment for their arrhythmia or that stopping or starting the cannabinoids affected the arrhythmia one way or the other,” he said. “In addition, there is no dose/arrhythmia relationship.”

More patients in the medicinal cannabis group than in the nonuser group were also taking opioids (49% vs. 30%), nonsteroidal anti-inflammatory drugs (24% vs. 19%), antiepileptics (35% vs. 23%), or tricyclic antidepressants (11% vs. 4%), he noted.

In summary, according to Dr. Olshansky, “these data pose no obvious health concern and provide no vital knowledge for physicians prescribing cannabis.”

“My concern is that the information will be overblown,” he cautioned. “If the cannabinoid actually has benefit in terms of pain reduction, its use may be mitigated based on the fear of an arrhythmia that may occur – but the risk of an arrhythmia, in any event, is very small and undefined in terms of its seriousness.”
 

Cancer, musculoskeletal, and neurologic pain

For this analysis, the researchers identified 1.8 million patients in Denmark who were diagnosed with chronic pain between 2018 and 2021.

Of those, around 5,000 patients had claimed at least one prescription of medicinal cannabis (dronabinol 29%, cannabinoids 46%, or cannabidiol 25%).

The patients had a median age of 60 years, and 63% were women.

The cannabis users had been prescribed this therapy for musculoskeletal (35%), cancer (18%), neurological (14%), or other (33%) pain, Dr. Nouhravesh said. 

The researchers and Dr. Olshansky have no relevant financial disclosures.  

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

Patients who received a first prescription for medicinal cannabis for chronic pain were more likely to have new onset of arrhythmia – bradyarrhythmia, tachyarrhythmia, or a conduction disorder – within 6 months than were similar nonusers, in a new case-control study.

VladK213/Getty Images

There were no between-group differences in the incidence of heart failure or acute coronary syndrome.

The researchers identified 5,071 patients in a national Danish registry who had filled at least one prescription for medicinal cannabis for chronic pain and matched each patient with five patients of the same sex, age range, and type of chronic pain who did not receive this therapy.

The relative risk for arrhythmia was 83% higher in those who used medicinal cannabis than it was in the other patients, study author Nina Nouhravesh, MD, told this news organization in an email.

However, the absolute risks for arrhythmia were slight – a 0.86% risk (95% confidence interval, 0.61%-1.1%) in medicinal cannabis users versus a 0.47% risk (95% CI, 0.38%-0.56%) in those who did not use medicinal cannabis.

“Since medical cannabis is a relatively new drug for a large market of patients with chronic pain, it is important to investigate and report serious side effects,” said Dr. Nouhravesh, from Gentofte University Hospital, Denmark.

The study results, she said, suggest that “there may be a previously unreported risk of arrhythmias following medical cannabis use.”

“Even though the absolute risk difference is small, both patients and physicians should have as much information as possible when weighing up the pros and cons of any treatment,” Dr. Nouhravesh said, adding that “the findings of this study raise concerns for both legal and illegal [cannabis] use worldwide.”

The results will be presented at the annual European Society of Cardiology (ESC) Congress 2022.
 

Too soon to tell?

However, Brian Olshansky, MD, who was not involved with this research, cautions that it is important to consider several study limitations before drawing clinical implications.

“Other data and reports have considered the possibility of arrhythmias in relationship to marijuana use, and the data go in both directions,” Dr. Olshansky, a clinical cardiac electrophysiologist and professor emeritus at University of Iowa Hospitals, Iowa City, pointed out in an email.

“Importantly, arrhythmias, by themselves, are not necessarily consequential,” he stressed. “In any case,” he added, the risks in the current study are “extraordinarily small.”

Sinus bradycardia, sinus tachycardia, and premature atrial or ventricular contractions could be totally benign, he said. On the other hand, arrhythmias may indicate the presence of atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation, which are potentially dangerous.

There may be a specific “high risk” group who can develop potentially serious arrhythmias, Dr. Olshansky suggested.

“There is no evidence that any of these patients underwent or required any treatment for their arrhythmia or that stopping or starting the cannabinoids affected the arrhythmia one way or the other,” he said. “In addition, there is no dose/arrhythmia relationship.”

More patients in the medicinal cannabis group than in the nonuser group were also taking opioids (49% vs. 30%), nonsteroidal anti-inflammatory drugs (24% vs. 19%), antiepileptics (35% vs. 23%), or tricyclic antidepressants (11% vs. 4%), he noted.

In summary, according to Dr. Olshansky, “these data pose no obvious health concern and provide no vital knowledge for physicians prescribing cannabis.”

“My concern is that the information will be overblown,” he cautioned. “If the cannabinoid actually has benefit in terms of pain reduction, its use may be mitigated based on the fear of an arrhythmia that may occur – but the risk of an arrhythmia, in any event, is very small and undefined in terms of its seriousness.”
 

Cancer, musculoskeletal, and neurologic pain

For this analysis, the researchers identified 1.8 million patients in Denmark who were diagnosed with chronic pain between 2018 and 2021.

Of those, around 5,000 patients had claimed at least one prescription of medicinal cannabis (dronabinol 29%, cannabinoids 46%, or cannabidiol 25%).

The patients had a median age of 60 years, and 63% were women.

The cannabis users had been prescribed this therapy for musculoskeletal (35%), cancer (18%), neurological (14%), or other (33%) pain, Dr. Nouhravesh said. 

The researchers and Dr. Olshansky have no relevant financial disclosures.  

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

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

Older adults with atrial cardiopathy may have up to 35% higher risk for dementia even before symptoms develop, new research suggests.

“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.

The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.

Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.

If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.

For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.

They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.

Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.

Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).

They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m² by transthoracic echocardiography.

The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).

The authors point out, however, that this study is observational and cannot make a causal link.

Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.

He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”

“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
 

Unresolved questions

But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.

He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.

Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”

There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.

He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”

The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.

Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.

“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.

Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.

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

Older adults with atrial cardiopathy may have up to 35% higher risk for dementia even before symptoms develop, new research suggests.

“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.

The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.

Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.

If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.

For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.

They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.

Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.

Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).

They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m² by transthoracic echocardiography.

The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).

The authors point out, however, that this study is observational and cannot make a causal link.

Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.

He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”

“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
 

Unresolved questions

But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.

He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.

Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”

There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.

He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”

The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.

Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.

“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.

Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.

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

Older adults with atrial cardiopathy may have up to 35% higher risk for dementia even before symptoms develop, new research suggests.

“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.

The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.

Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.

If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.

For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.

They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.

Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.

Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).

They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m² by transthoracic echocardiography.

The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).

The authors point out, however, that this study is observational and cannot make a causal link.

Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.

He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”

“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
 

Unresolved questions

But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.

He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.

Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”

There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.

He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”

The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.

Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.

“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.

Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.

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

Symptoms of six common cardiovascular diseases (CVD) – acute coronary syndromes, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease – often overlap and may vary over time and by sex, the American Heart Association noted in a new scientific statement.

“Symptoms of these cardiovascular diseases can profoundly affect quality of life, and a clear understanding of them is critical for effective diagnosis and treatment decisions,” Corrine Y. Jurgens, PhD, chair of the writing committee, said in a news release.

Copyright pixelheadphoto/Thinkstock

This scientific statement is a “compendium detailing the symptoms associated with CVD, similarities or differences in symptoms among the conditions, and sex differences in symptom presentation and reporting,” said Dr. Jurgens, associate professor at Connell School of Nursing, Boston College.

The new statement was published online in Circulation.

The writing group noted that measuring CVD symptoms can be challenging because of their subjective nature. Symptoms may go unrecognized or unreported if people don’t think they are important or are related to an existing health condition.

“Some people may not consider symptoms like fatigue, sleep disturbance, weight gain, and depression as important or related to cardiovascular disease. However, research indicates that subtle symptoms such as these may predict acute events and the need for hospitalization,” Dr. Jurgens said.
 

ACS – chest pain and associated symptoms

The writing group noted that chest pain is the most frequently reported symptom of ACS and has often been described as substernal pressure or discomfort and may radiate to the jaw, shoulder, arm, or upper back.

The most common co-occurring symptoms are dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness. Women are more likely than men to report additional symptoms outside of chest pain.

As a result, they have often been labeled “atypical.” However, a recent AHA advisory notes that this label may have been caused by the lack of women included in the clinical trials from which the symptom lists were derived.

The writing group said there is a need to “harmonize” ACS symptom measurement in research. The current lack of harmonization of ACS symptom measurement in research hampers growth in cumulative evidence.

“Therefore, little can be done to synthesize salient findings about symptoms across ischemic heart disease/ACS studies and to incorporate evidence-based information about symptoms into treatment guidelines and patient education materials,” they cautioned. 
 

Heart failure

Turning to heart failure (HF), the writing group noted that dyspnea is the classic symptom and a common reason adults seek medical care.

However, early, more subtle symptoms should be recognized. These include gastrointestinal symptoms such as upset stomach, nausea, vomiting, and loss of appetite; fatigue; exercise intolerance; insomnia; pain (chest and otherwise); mood disturbances (primarily depression and anxiety); and cognitive dysfunction (brain fog, memory problems).

Women with HF report a wider variety of symptoms, are more likely to have depression and anxiety, and report a lower quality of life, compared with men with HF.

“It is important to account for dyspnea heterogeneity in both clinical practice and research by using nuanced measures and probing questions to capture this common and multifaceted symptom,” the writing group said.

“Monitoring symptoms on a spectrum, versus present or not present, with reliable and valid measures may enhance clinical care by identifying more quickly those who may be at risk for poor outcomes, such as lower quality of life, hospitalization, or death,” Dr. Jurgens added.

“Ultimately, we have work to do in terms of determining who needs more frequent monitoring or intervention to avert poor HF outcomes,” she said.
 

Valvular heart disease

Valvular heart disease is a frequent cause of HF, with symptoms generally indistinguishable from other HF causes. Rheumatic heart disease is still prevalent in low- and middle-income countries but has largely disappeared in high-income countries, with population aging and cardiomyopathies now key drivers of valve disease.

In the absence of acute severe valve dysfunction, patients generally have a prolonged asymptomatic period, followed by a period of progressive symptoms, resulting from the valve lesion itself or secondary myocardial remodeling and dysfunction, the writing group said. 

Symptoms of aortic valve disease often differ between men and women. Aortic stenosis is typically silent for years. As stenosis progresses, women report dyspnea and exercise intolerance more often than men. Women are also more likely to be physically frail and to have a higher New York Heart Association class (III/IV) than men. Men are more likely to have chest pain.

“Given the importance of symptom assessment, more work is needed to determine the incremental value of quantitative symptom measurement as an aid to clinical management,” the writing group said.
 

Stroke

For clinicians, classic stroke symptoms (face drooping, arm weakness, speech difficulty), in addition to nonclassic symptoms, such as partial sensory deficit, dysarthria, vertigo, and diplopia, should be considered for activating a stroke response team, the group says.

A systematic review and meta-analysis revealed that women with stroke were more likely to present with nonfocal symptoms (for example, headache, altered mentality, and coma/stupor) than men, they noted.

To enhance public education about stroke symptoms and to facilitate the diagnosis and treatment of stroke, they say research is needed to better understand the presentation of stroke symptoms by other select demographic characteristics including race and ethnicity, age, and stroke subtype.

Poststroke screening should include assessment for anxiety, depression, fatigue, and pain, the writing group said.
 

Rhythm disorders

Turning to rhythm disorders, the writing group wrote that cardiac arrhythmias, including atrial fibrillation (AFib), atrial flutter, supraventricular tachycardia, bradyarrhythmia, and ventricular tachycardia, present with common symptoms.

Palpitations are a characteristic symptom of many cardiac arrhythmias. The most common cardiac arrhythmia, AFib, may present with palpitations or less specific symptoms (fatigue, dyspnea, dizziness) that occur with a broad range of rhythm disorders. Chest pain, dizziness, presyncope/syncope, and anxiety occur less frequently in AFib, the group said.

Palpitations are considered the typical symptom presentation for AFib, yet patients with new-onset AFib often present with nonspecific symptoms or no symptoms, they pointed out.

Women and younger individuals with AFib typically present with palpitations, whereas men are more commonly asymptomatic. Older age also increases the likelihood of a nonclassic or asymptomatic presentation of AFib.

Despite non-Hispanic Black individuals being at lower risk for development of AFib, research suggests that Black patients are burdened more with palpitations, dyspnea on exertion, exercise intolerance, dizziness, dyspnea at rest, and chest discomfort, compared with White or Hispanic patients.

Peripheral vascular disease

Classic claudication occurs in roughly one-third of patients with peripheral arterial disease (PAD) and is defined as calf pain that occurs in one or both legs with exertion (walking), does not begin at rest, and resolves within 10 minutes of standing still or rest.

However, non–calf exercise pain is reported more frequently than classic claudication symptoms. Women with PAD are more likely to have nonclassic symptoms or an absence of symptoms.

Assessing symptoms at rest, during exercise, and during recovery can assist with classifying symptoms as ischemic or not, the writing group said.

PAD with symptoms is associated with an increased risk for myocardial infarction and stroke, with men at higher risk than women.

Similar to PAD, peripheral venous disease (PVD) can be symptomatic or asymptomatic. Clinical classification of PVD includes symptoms such as leg pain, aching, fatigue, heaviness, cramping, tightness, restless legs syndrome, and skin irritation.

“Measuring vascular symptoms includes assessing quality of life and activity limitations, as well as the psychological impact of the disease. However, existing measures are often based on the clinician’s appraisal rather than the individual’s self-reported symptoms and severity of symptoms,” Dr. Jurgens commented.
 

Watch for depression

Finally, the writing group highlighted the importance of depression in cardiac patients, which occurs at about twice the rate, compared with people without any medical condition (10% vs. 5%).

In a prior statement, the AHA said depression should be considered a risk factor for worse outcomes in patients with ACS or CVD diagnosis.

The new statement highlights that people with persistent chest pain, people with HF, as well as stroke survivors and people with PAD commonly have depression and/or anxiety. In addition, cognitive changes after a stroke may affect how and whether symptoms are experienced or noticed.

While symptom relief is an important part of managing CVD, it’s also important to recognize that “factors such as depression and cognitive function may affect symptom detection and reporting,” Dr. Jurgens said.

“Monitoring and measuring symptoms with tools that appropriately account for depression and cognitive function may help to improve patient care by identifying more quickly people who may be at higher risk,” she added.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing; the Council on Hypertension; and the Stroke Council. The research had no commercial funding. The authors reported no relevant financial relationships.

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

Symptoms of six common cardiovascular diseases (CVD) – acute coronary syndromes, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease – often overlap and may vary over time and by sex, the American Heart Association noted in a new scientific statement.

“Symptoms of these cardiovascular diseases can profoundly affect quality of life, and a clear understanding of them is critical for effective diagnosis and treatment decisions,” Corrine Y. Jurgens, PhD, chair of the writing committee, said in a news release.

Copyright pixelheadphoto/Thinkstock

This scientific statement is a “compendium detailing the symptoms associated with CVD, similarities or differences in symptoms among the conditions, and sex differences in symptom presentation and reporting,” said Dr. Jurgens, associate professor at Connell School of Nursing, Boston College.

The new statement was published online in Circulation.

The writing group noted that measuring CVD symptoms can be challenging because of their subjective nature. Symptoms may go unrecognized or unreported if people don’t think they are important or are related to an existing health condition.

“Some people may not consider symptoms like fatigue, sleep disturbance, weight gain, and depression as important or related to cardiovascular disease. However, research indicates that subtle symptoms such as these may predict acute events and the need for hospitalization,” Dr. Jurgens said.
 

ACS – chest pain and associated symptoms

The writing group noted that chest pain is the most frequently reported symptom of ACS and has often been described as substernal pressure or discomfort and may radiate to the jaw, shoulder, arm, or upper back.

The most common co-occurring symptoms are dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness. Women are more likely than men to report additional symptoms outside of chest pain.

As a result, they have often been labeled “atypical.” However, a recent AHA advisory notes that this label may have been caused by the lack of women included in the clinical trials from which the symptom lists were derived.

The writing group said there is a need to “harmonize” ACS symptom measurement in research. The current lack of harmonization of ACS symptom measurement in research hampers growth in cumulative evidence.

“Therefore, little can be done to synthesize salient findings about symptoms across ischemic heart disease/ACS studies and to incorporate evidence-based information about symptoms into treatment guidelines and patient education materials,” they cautioned. 
 

Heart failure

Turning to heart failure (HF), the writing group noted that dyspnea is the classic symptom and a common reason adults seek medical care.

However, early, more subtle symptoms should be recognized. These include gastrointestinal symptoms such as upset stomach, nausea, vomiting, and loss of appetite; fatigue; exercise intolerance; insomnia; pain (chest and otherwise); mood disturbances (primarily depression and anxiety); and cognitive dysfunction (brain fog, memory problems).

Women with HF report a wider variety of symptoms, are more likely to have depression and anxiety, and report a lower quality of life, compared with men with HF.

“It is important to account for dyspnea heterogeneity in both clinical practice and research by using nuanced measures and probing questions to capture this common and multifaceted symptom,” the writing group said.

“Monitoring symptoms on a spectrum, versus present or not present, with reliable and valid measures may enhance clinical care by identifying more quickly those who may be at risk for poor outcomes, such as lower quality of life, hospitalization, or death,” Dr. Jurgens added.

“Ultimately, we have work to do in terms of determining who needs more frequent monitoring or intervention to avert poor HF outcomes,” she said.
 

Valvular heart disease

Valvular heart disease is a frequent cause of HF, with symptoms generally indistinguishable from other HF causes. Rheumatic heart disease is still prevalent in low- and middle-income countries but has largely disappeared in high-income countries, with population aging and cardiomyopathies now key drivers of valve disease.

In the absence of acute severe valve dysfunction, patients generally have a prolonged asymptomatic period, followed by a period of progressive symptoms, resulting from the valve lesion itself or secondary myocardial remodeling and dysfunction, the writing group said. 

Symptoms of aortic valve disease often differ between men and women. Aortic stenosis is typically silent for years. As stenosis progresses, women report dyspnea and exercise intolerance more often than men. Women are also more likely to be physically frail and to have a higher New York Heart Association class (III/IV) than men. Men are more likely to have chest pain.

“Given the importance of symptom assessment, more work is needed to determine the incremental value of quantitative symptom measurement as an aid to clinical management,” the writing group said.
 

Stroke

For clinicians, classic stroke symptoms (face drooping, arm weakness, speech difficulty), in addition to nonclassic symptoms, such as partial sensory deficit, dysarthria, vertigo, and diplopia, should be considered for activating a stroke response team, the group says.

A systematic review and meta-analysis revealed that women with stroke were more likely to present with nonfocal symptoms (for example, headache, altered mentality, and coma/stupor) than men, they noted.

To enhance public education about stroke symptoms and to facilitate the diagnosis and treatment of stroke, they say research is needed to better understand the presentation of stroke symptoms by other select demographic characteristics including race and ethnicity, age, and stroke subtype.

Poststroke screening should include assessment for anxiety, depression, fatigue, and pain, the writing group said.
 

Rhythm disorders

Turning to rhythm disorders, the writing group wrote that cardiac arrhythmias, including atrial fibrillation (AFib), atrial flutter, supraventricular tachycardia, bradyarrhythmia, and ventricular tachycardia, present with common symptoms.

Palpitations are a characteristic symptom of many cardiac arrhythmias. The most common cardiac arrhythmia, AFib, may present with palpitations or less specific symptoms (fatigue, dyspnea, dizziness) that occur with a broad range of rhythm disorders. Chest pain, dizziness, presyncope/syncope, and anxiety occur less frequently in AFib, the group said.

Palpitations are considered the typical symptom presentation for AFib, yet patients with new-onset AFib often present with nonspecific symptoms or no symptoms, they pointed out.

Women and younger individuals with AFib typically present with palpitations, whereas men are more commonly asymptomatic. Older age also increases the likelihood of a nonclassic or asymptomatic presentation of AFib.

Despite non-Hispanic Black individuals being at lower risk for development of AFib, research suggests that Black patients are burdened more with palpitations, dyspnea on exertion, exercise intolerance, dizziness, dyspnea at rest, and chest discomfort, compared with White or Hispanic patients.

Peripheral vascular disease

Classic claudication occurs in roughly one-third of patients with peripheral arterial disease (PAD) and is defined as calf pain that occurs in one or both legs with exertion (walking), does not begin at rest, and resolves within 10 minutes of standing still or rest.

However, non–calf exercise pain is reported more frequently than classic claudication symptoms. Women with PAD are more likely to have nonclassic symptoms or an absence of symptoms.

Assessing symptoms at rest, during exercise, and during recovery can assist with classifying symptoms as ischemic or not, the writing group said.

PAD with symptoms is associated with an increased risk for myocardial infarction and stroke, with men at higher risk than women.

Similar to PAD, peripheral venous disease (PVD) can be symptomatic or asymptomatic. Clinical classification of PVD includes symptoms such as leg pain, aching, fatigue, heaviness, cramping, tightness, restless legs syndrome, and skin irritation.

“Measuring vascular symptoms includes assessing quality of life and activity limitations, as well as the psychological impact of the disease. However, existing measures are often based on the clinician’s appraisal rather than the individual’s self-reported symptoms and severity of symptoms,” Dr. Jurgens commented.
 

Watch for depression

Finally, the writing group highlighted the importance of depression in cardiac patients, which occurs at about twice the rate, compared with people without any medical condition (10% vs. 5%).

In a prior statement, the AHA said depression should be considered a risk factor for worse outcomes in patients with ACS or CVD diagnosis.

The new statement highlights that people with persistent chest pain, people with HF, as well as stroke survivors and people with PAD commonly have depression and/or anxiety. In addition, cognitive changes after a stroke may affect how and whether symptoms are experienced or noticed.

While symptom relief is an important part of managing CVD, it’s also important to recognize that “factors such as depression and cognitive function may affect symptom detection and reporting,” Dr. Jurgens said.

“Monitoring and measuring symptoms with tools that appropriately account for depression and cognitive function may help to improve patient care by identifying more quickly people who may be at higher risk,” she added.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing; the Council on Hypertension; and the Stroke Council. The research had no commercial funding. The authors reported no relevant financial relationships.

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

Symptoms of six common cardiovascular diseases (CVD) – acute coronary syndromes, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease – often overlap and may vary over time and by sex, the American Heart Association noted in a new scientific statement.

“Symptoms of these cardiovascular diseases can profoundly affect quality of life, and a clear understanding of them is critical for effective diagnosis and treatment decisions,” Corrine Y. Jurgens, PhD, chair of the writing committee, said in a news release.

Copyright pixelheadphoto/Thinkstock

This scientific statement is a “compendium detailing the symptoms associated with CVD, similarities or differences in symptoms among the conditions, and sex differences in symptom presentation and reporting,” said Dr. Jurgens, associate professor at Connell School of Nursing, Boston College.

The new statement was published online in Circulation.

The writing group noted that measuring CVD symptoms can be challenging because of their subjective nature. Symptoms may go unrecognized or unreported if people don’t think they are important or are related to an existing health condition.

“Some people may not consider symptoms like fatigue, sleep disturbance, weight gain, and depression as important or related to cardiovascular disease. However, research indicates that subtle symptoms such as these may predict acute events and the need for hospitalization,” Dr. Jurgens said.
 

ACS – chest pain and associated symptoms

The writing group noted that chest pain is the most frequently reported symptom of ACS and has often been described as substernal pressure or discomfort and may radiate to the jaw, shoulder, arm, or upper back.

The most common co-occurring symptoms are dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness. Women are more likely than men to report additional symptoms outside of chest pain.

As a result, they have often been labeled “atypical.” However, a recent AHA advisory notes that this label may have been caused by the lack of women included in the clinical trials from which the symptom lists were derived.

The writing group said there is a need to “harmonize” ACS symptom measurement in research. The current lack of harmonization of ACS symptom measurement in research hampers growth in cumulative evidence.

“Therefore, little can be done to synthesize salient findings about symptoms across ischemic heart disease/ACS studies and to incorporate evidence-based information about symptoms into treatment guidelines and patient education materials,” they cautioned. 
 

Heart failure

Turning to heart failure (HF), the writing group noted that dyspnea is the classic symptom and a common reason adults seek medical care.

However, early, more subtle symptoms should be recognized. These include gastrointestinal symptoms such as upset stomach, nausea, vomiting, and loss of appetite; fatigue; exercise intolerance; insomnia; pain (chest and otherwise); mood disturbances (primarily depression and anxiety); and cognitive dysfunction (brain fog, memory problems).

Women with HF report a wider variety of symptoms, are more likely to have depression and anxiety, and report a lower quality of life, compared with men with HF.

“It is important to account for dyspnea heterogeneity in both clinical practice and research by using nuanced measures and probing questions to capture this common and multifaceted symptom,” the writing group said.

“Monitoring symptoms on a spectrum, versus present or not present, with reliable and valid measures may enhance clinical care by identifying more quickly those who may be at risk for poor outcomes, such as lower quality of life, hospitalization, or death,” Dr. Jurgens added.

“Ultimately, we have work to do in terms of determining who needs more frequent monitoring or intervention to avert poor HF outcomes,” she said.
 

Valvular heart disease

Valvular heart disease is a frequent cause of HF, with symptoms generally indistinguishable from other HF causes. Rheumatic heart disease is still prevalent in low- and middle-income countries but has largely disappeared in high-income countries, with population aging and cardiomyopathies now key drivers of valve disease.

In the absence of acute severe valve dysfunction, patients generally have a prolonged asymptomatic period, followed by a period of progressive symptoms, resulting from the valve lesion itself or secondary myocardial remodeling and dysfunction, the writing group said. 

Symptoms of aortic valve disease often differ between men and women. Aortic stenosis is typically silent for years. As stenosis progresses, women report dyspnea and exercise intolerance more often than men. Women are also more likely to be physically frail and to have a higher New York Heart Association class (III/IV) than men. Men are more likely to have chest pain.

“Given the importance of symptom assessment, more work is needed to determine the incremental value of quantitative symptom measurement as an aid to clinical management,” the writing group said.
 

Stroke

For clinicians, classic stroke symptoms (face drooping, arm weakness, speech difficulty), in addition to nonclassic symptoms, such as partial sensory deficit, dysarthria, vertigo, and diplopia, should be considered for activating a stroke response team, the group says.

A systematic review and meta-analysis revealed that women with stroke were more likely to present with nonfocal symptoms (for example, headache, altered mentality, and coma/stupor) than men, they noted.

To enhance public education about stroke symptoms and to facilitate the diagnosis and treatment of stroke, they say research is needed to better understand the presentation of stroke symptoms by other select demographic characteristics including race and ethnicity, age, and stroke subtype.

Poststroke screening should include assessment for anxiety, depression, fatigue, and pain, the writing group said.
 

Rhythm disorders

Turning to rhythm disorders, the writing group wrote that cardiac arrhythmias, including atrial fibrillation (AFib), atrial flutter, supraventricular tachycardia, bradyarrhythmia, and ventricular tachycardia, present with common symptoms.

Palpitations are a characteristic symptom of many cardiac arrhythmias. The most common cardiac arrhythmia, AFib, may present with palpitations or less specific symptoms (fatigue, dyspnea, dizziness) that occur with a broad range of rhythm disorders. Chest pain, dizziness, presyncope/syncope, and anxiety occur less frequently in AFib, the group said.

Palpitations are considered the typical symptom presentation for AFib, yet patients with new-onset AFib often present with nonspecific symptoms or no symptoms, they pointed out.

Women and younger individuals with AFib typically present with palpitations, whereas men are more commonly asymptomatic. Older age also increases the likelihood of a nonclassic or asymptomatic presentation of AFib.

Despite non-Hispanic Black individuals being at lower risk for development of AFib, research suggests that Black patients are burdened more with palpitations, dyspnea on exertion, exercise intolerance, dizziness, dyspnea at rest, and chest discomfort, compared with White or Hispanic patients.

Peripheral vascular disease

Classic claudication occurs in roughly one-third of patients with peripheral arterial disease (PAD) and is defined as calf pain that occurs in one or both legs with exertion (walking), does not begin at rest, and resolves within 10 minutes of standing still or rest.

However, non–calf exercise pain is reported more frequently than classic claudication symptoms. Women with PAD are more likely to have nonclassic symptoms or an absence of symptoms.

Assessing symptoms at rest, during exercise, and during recovery can assist with classifying symptoms as ischemic or not, the writing group said.

PAD with symptoms is associated with an increased risk for myocardial infarction and stroke, with men at higher risk than women.

Similar to PAD, peripheral venous disease (PVD) can be symptomatic or asymptomatic. Clinical classification of PVD includes symptoms such as leg pain, aching, fatigue, heaviness, cramping, tightness, restless legs syndrome, and skin irritation.

“Measuring vascular symptoms includes assessing quality of life and activity limitations, as well as the psychological impact of the disease. However, existing measures are often based on the clinician’s appraisal rather than the individual’s self-reported symptoms and severity of symptoms,” Dr. Jurgens commented.
 

Watch for depression

Finally, the writing group highlighted the importance of depression in cardiac patients, which occurs at about twice the rate, compared with people without any medical condition (10% vs. 5%).

In a prior statement, the AHA said depression should be considered a risk factor for worse outcomes in patients with ACS or CVD diagnosis.

The new statement highlights that people with persistent chest pain, people with HF, as well as stroke survivors and people with PAD commonly have depression and/or anxiety. In addition, cognitive changes after a stroke may affect how and whether symptoms are experienced or noticed.

While symptom relief is an important part of managing CVD, it’s also important to recognize that “factors such as depression and cognitive function may affect symptom detection and reporting,” Dr. Jurgens said.

“Monitoring and measuring symptoms with tools that appropriately account for depression and cognitive function may help to improve patient care by identifying more quickly people who may be at higher risk,” she added.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing; the Council on Hypertension; and the Stroke Council. The research had no commercial funding. The authors reported no relevant financial relationships.

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