Arrhythmias & EP

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

People with paroxysmal atrial fibrillation who explored potential triggers of their arrhythmia, and used them to make lifestyle changes, went on to show a 40% decline in subjectively experienced bouts of AFib in a randomized trial with an unusual design.

American Heart Association

But the study didn’t provide evidence that the drop in self-reported AFib necessarily improved their quality of life, its primary endpoint. Nor was there any apparent relationship between potential triggers and AFib episodes detected less subjectively using a handheld electrocardiography monitor.

Although the study – called I-STOP-AFib – has limitations, its results jibe with alcohol intake’s increasingly appreciated status as a potential AFib trigger. It was alone among many possible triggers tested in showing a consistent association with self-reported AFib.

As a result, the study offers no support for such a link between the arrhythmia and caffeine intake, sleep deprivation, dehydration, exercise, or other conditions sometimes perceived as triggers, observed principal investigator Gregory M. Marcus, MD, MAS, University of California, San Francisco, when presenting results at the American Heart Association scientific sessions. He is also lead author on the study’s simultaneous publication in JAMA Cardiology.

The I-STOP-AFib trial was unusual in part for its virtual design, in which participants followed instructions and tracked AFib episodes – both perceived and detected by the handheld ECG device – through a smartphone application. It also featured an N-of-1 randomized comparisons of different weeks in which individuals were or were not exposed to their self-selected trigger.

Such patients following their own weekly personalized randomization were compared to an entirely separate randomized control arm of the trial, in which patients simply tracked any ECG-monitored and self-perceived AFib episodes.
 

Current use in patients

Although wearable and smartphone-based ECG recorders are increasingly popular for AFib screening, Dr. Marcus said the devices may be especially helpful for validating whether a person’s symptoms are actually caused by AFib.

“I have actually suggested to some of my patients that they run some of these experiments,” he said at a media briefing on I-STOP-AFib before his main presentation of the trial. The demonstration might help patients recognize that some perceived triggers actually do not induce AFib.

Allowing patients to determine on their own whether a substance indeed triggers their AFib “is an efficient use of these devices,” Dr. Marcus said. Such N-of-1 exploration of possible triggers “might help free patients up to enjoy substances – caffeine or coffee is one example – that they otherwise might not, and may help actually reassure them that certain exposures –like certain exercises, which can also be beneficial – might actually not be harmful.”

Dr. Marcus and the other authors on the report noted – as he did at the AHA sessions – that the study has several limitations, such as the subjectivity of self-reported AFib, dropouts from the trial that shrank the randomization arms, and a population that may not be very representative.

There is also the potential for detection bias in the group assigned to track their selected triggers, as Dr. Marcus and some observers have noted.

It follows that conscious avoidance of a potential AFib trigger might well lead to a reduction in AFib subjectively identified by symptoms, proposed David Conen, MD, MPH, Population Health Research Institute, McMaster University, Hamilton, Ont. But perhaps there would have been no reduction in AFib had it been objectively documented with the handheld ECG device, he said in an interview.

“If I were to redesign the study,” he said, “I think the primary endpoint should be confirmed atrial fibrillation, because we would have to show first that the specific trigger actually reduced objective AFib events before we then try to address the question whether reducing that trigger improves quality of life.”
 

Unrepresentative sample

The trial entered 446 overwhelmingly White and college-educated adults known to have symptomatic paroxysmal AFib who were “interested in testing a presumed AFib trigger they could readily introduce or withhold” and who owned a smartphone; the average age was 58 years, and 58% were men. The cohort was randomly assigned to the trigger-testing group or the control group, charged only with tracking their AFib.

Of the total, 320, or about 72%, completed the study; those who did not were mostly from the trigger-testing arm, leaving 136 in that group versus 184 patients in the control group.

Potential triggers that participants selected for tracking included, foremost, caffeine, alcohol, reduced sleep, and exercise, followed by lying on the left side, dehydration, large meals, and cold food or drink, the report noted.

Patients in the control group used the smartphone app and handheld ECG monitor (KardiaMobile, AliveCor) to document the duration and severity of AFib episodes daily and received data summary reports through the app weekly for 10 weeks. They then had the option to follow the trigger-testing protocol at least once.

Those in the trigger-testing group conducted their N-of-1 trials by exposing themselves to their chosen potential trigger during 3 separate weeks and avoiding the trigger during 3 other weeks, alternating each of the 6 weeks of trigger exposure or avoidance. They were instructed through the app to start the 6-week sequence with one or the other strategy randomly and to regularly track their AFib.

At the end of 6 weeks, each participant in the trigger-testing group had the opportunity to review their data for any potential trigger-AFib associations. They were then to use the next 4 weeks to enact lifestyle changes based on what they learned – as described in the report and on clinicaltrials.gov. They had the option of repeating the entire N-of-1 sequence at least one more time.

Participants in both the trigger-tracking and control arms were tested at baseline and at 10 weeks using the validated Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire.

AFEQT scores didn’t change significantly over the 10 weeks in either arm, nor were they significantly different in one arm, compared with the other.

On the other hand, patients in the trigger-tracking arm reported significantly fewer daily AFib episodes during the final 4-week period of lifestyle changes based on their N-of-1 trial results, compared to the monitoring-only control group’s final 4 weeks.

The adjusted relative risk in the trigger-tracking arm was 0.60 (95% confidence interval, 0.43-0.83; P < .001), the difference driven by patients who selected alcohol, dehydration, or exercise for their trigger, Dr. Marcus reported.

Only alcohol intake emerged consistently as a significant predictor of risk for self-reported AFib episodes in a series of meta-analyses conducted using all of the individual N-of-1 trials that provided per-protocol data. The odds ratio was 1.77 (95% CI, 1.20-2.69).

I-STOP-AFib explored an important subject “that has been understudied,” Dr. Conen said. “The trial has some limitations that the authors address themselves, but hopefully it opens the path to future studies that can build upon this experience.”

Dr. Marcus reported receiving personal fees and equity interest from InCarda Therapeutics; personal fees from Johnson & Johnson; and grants from Baylis Medical, Medtronic, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the California Tobacco-Related Disease Research Program.

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

People with paroxysmal atrial fibrillation who explored potential triggers of their arrhythmia, and used them to make lifestyle changes, went on to show a 40% decline in subjectively experienced bouts of AFib in a randomized trial with an unusual design.

American Heart Association

But the study didn’t provide evidence that the drop in self-reported AFib necessarily improved their quality of life, its primary endpoint. Nor was there any apparent relationship between potential triggers and AFib episodes detected less subjectively using a handheld electrocardiography monitor.

Although the study – called I-STOP-AFib – has limitations, its results jibe with alcohol intake’s increasingly appreciated status as a potential AFib trigger. It was alone among many possible triggers tested in showing a consistent association with self-reported AFib.

As a result, the study offers no support for such a link between the arrhythmia and caffeine intake, sleep deprivation, dehydration, exercise, or other conditions sometimes perceived as triggers, observed principal investigator Gregory M. Marcus, MD, MAS, University of California, San Francisco, when presenting results at the American Heart Association scientific sessions. He is also lead author on the study’s simultaneous publication in JAMA Cardiology.

The I-STOP-AFib trial was unusual in part for its virtual design, in which participants followed instructions and tracked AFib episodes – both perceived and detected by the handheld ECG device – through a smartphone application. It also featured an N-of-1 randomized comparisons of different weeks in which individuals were or were not exposed to their self-selected trigger.

Such patients following their own weekly personalized randomization were compared to an entirely separate randomized control arm of the trial, in which patients simply tracked any ECG-monitored and self-perceived AFib episodes.
 

Current use in patients

Although wearable and smartphone-based ECG recorders are increasingly popular for AFib screening, Dr. Marcus said the devices may be especially helpful for validating whether a person’s symptoms are actually caused by AFib.

“I have actually suggested to some of my patients that they run some of these experiments,” he said at a media briefing on I-STOP-AFib before his main presentation of the trial. The demonstration might help patients recognize that some perceived triggers actually do not induce AFib.

Allowing patients to determine on their own whether a substance indeed triggers their AFib “is an efficient use of these devices,” Dr. Marcus said. Such N-of-1 exploration of possible triggers “might help free patients up to enjoy substances – caffeine or coffee is one example – that they otherwise might not, and may help actually reassure them that certain exposures –like certain exercises, which can also be beneficial – might actually not be harmful.”

Dr. Marcus and the other authors on the report noted – as he did at the AHA sessions – that the study has several limitations, such as the subjectivity of self-reported AFib, dropouts from the trial that shrank the randomization arms, and a population that may not be very representative.

There is also the potential for detection bias in the group assigned to track their selected triggers, as Dr. Marcus and some observers have noted.

It follows that conscious avoidance of a potential AFib trigger might well lead to a reduction in AFib subjectively identified by symptoms, proposed David Conen, MD, MPH, Population Health Research Institute, McMaster University, Hamilton, Ont. But perhaps there would have been no reduction in AFib had it been objectively documented with the handheld ECG device, he said in an interview.

“If I were to redesign the study,” he said, “I think the primary endpoint should be confirmed atrial fibrillation, because we would have to show first that the specific trigger actually reduced objective AFib events before we then try to address the question whether reducing that trigger improves quality of life.”
 

Unrepresentative sample

The trial entered 446 overwhelmingly White and college-educated adults known to have symptomatic paroxysmal AFib who were “interested in testing a presumed AFib trigger they could readily introduce or withhold” and who owned a smartphone; the average age was 58 years, and 58% were men. The cohort was randomly assigned to the trigger-testing group or the control group, charged only with tracking their AFib.

Of the total, 320, or about 72%, completed the study; those who did not were mostly from the trigger-testing arm, leaving 136 in that group versus 184 patients in the control group.

Potential triggers that participants selected for tracking included, foremost, caffeine, alcohol, reduced sleep, and exercise, followed by lying on the left side, dehydration, large meals, and cold food or drink, the report noted.

Patients in the control group used the smartphone app and handheld ECG monitor (KardiaMobile, AliveCor) to document the duration and severity of AFib episodes daily and received data summary reports through the app weekly for 10 weeks. They then had the option to follow the trigger-testing protocol at least once.

Those in the trigger-testing group conducted their N-of-1 trials by exposing themselves to their chosen potential trigger during 3 separate weeks and avoiding the trigger during 3 other weeks, alternating each of the 6 weeks of trigger exposure or avoidance. They were instructed through the app to start the 6-week sequence with one or the other strategy randomly and to regularly track their AFib.

At the end of 6 weeks, each participant in the trigger-testing group had the opportunity to review their data for any potential trigger-AFib associations. They were then to use the next 4 weeks to enact lifestyle changes based on what they learned – as described in the report and on clinicaltrials.gov. They had the option of repeating the entire N-of-1 sequence at least one more time.

Participants in both the trigger-tracking and control arms were tested at baseline and at 10 weeks using the validated Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire.

AFEQT scores didn’t change significantly over the 10 weeks in either arm, nor were they significantly different in one arm, compared with the other.

On the other hand, patients in the trigger-tracking arm reported significantly fewer daily AFib episodes during the final 4-week period of lifestyle changes based on their N-of-1 trial results, compared to the monitoring-only control group’s final 4 weeks.

The adjusted relative risk in the trigger-tracking arm was 0.60 (95% confidence interval, 0.43-0.83; P < .001), the difference driven by patients who selected alcohol, dehydration, or exercise for their trigger, Dr. Marcus reported.

Only alcohol intake emerged consistently as a significant predictor of risk for self-reported AFib episodes in a series of meta-analyses conducted using all of the individual N-of-1 trials that provided per-protocol data. The odds ratio was 1.77 (95% CI, 1.20-2.69).

I-STOP-AFib explored an important subject “that has been understudied,” Dr. Conen said. “The trial has some limitations that the authors address themselves, but hopefully it opens the path to future studies that can build upon this experience.”

Dr. Marcus reported receiving personal fees and equity interest from InCarda Therapeutics; personal fees from Johnson & Johnson; and grants from Baylis Medical, Medtronic, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the California Tobacco-Related Disease Research Program.

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

People with paroxysmal atrial fibrillation who explored potential triggers of their arrhythmia, and used them to make lifestyle changes, went on to show a 40% decline in subjectively experienced bouts of AFib in a randomized trial with an unusual design.

American Heart Association

But the study didn’t provide evidence that the drop in self-reported AFib necessarily improved their quality of life, its primary endpoint. Nor was there any apparent relationship between potential triggers and AFib episodes detected less subjectively using a handheld electrocardiography monitor.

Although the study – called I-STOP-AFib – has limitations, its results jibe with alcohol intake’s increasingly appreciated status as a potential AFib trigger. It was alone among many possible triggers tested in showing a consistent association with self-reported AFib.

As a result, the study offers no support for such a link between the arrhythmia and caffeine intake, sleep deprivation, dehydration, exercise, or other conditions sometimes perceived as triggers, observed principal investigator Gregory M. Marcus, MD, MAS, University of California, San Francisco, when presenting results at the American Heart Association scientific sessions. He is also lead author on the study’s simultaneous publication in JAMA Cardiology.

The I-STOP-AFib trial was unusual in part for its virtual design, in which participants followed instructions and tracked AFib episodes – both perceived and detected by the handheld ECG device – through a smartphone application. It also featured an N-of-1 randomized comparisons of different weeks in which individuals were or were not exposed to their self-selected trigger.

Such patients following their own weekly personalized randomization were compared to an entirely separate randomized control arm of the trial, in which patients simply tracked any ECG-monitored and self-perceived AFib episodes.
 

Current use in patients

Although wearable and smartphone-based ECG recorders are increasingly popular for AFib screening, Dr. Marcus said the devices may be especially helpful for validating whether a person’s symptoms are actually caused by AFib.

“I have actually suggested to some of my patients that they run some of these experiments,” he said at a media briefing on I-STOP-AFib before his main presentation of the trial. The demonstration might help patients recognize that some perceived triggers actually do not induce AFib.

Allowing patients to determine on their own whether a substance indeed triggers their AFib “is an efficient use of these devices,” Dr. Marcus said. Such N-of-1 exploration of possible triggers “might help free patients up to enjoy substances – caffeine or coffee is one example – that they otherwise might not, and may help actually reassure them that certain exposures –like certain exercises, which can also be beneficial – might actually not be harmful.”

Dr. Marcus and the other authors on the report noted – as he did at the AHA sessions – that the study has several limitations, such as the subjectivity of self-reported AFib, dropouts from the trial that shrank the randomization arms, and a population that may not be very representative.

There is also the potential for detection bias in the group assigned to track their selected triggers, as Dr. Marcus and some observers have noted.

It follows that conscious avoidance of a potential AFib trigger might well lead to a reduction in AFib subjectively identified by symptoms, proposed David Conen, MD, MPH, Population Health Research Institute, McMaster University, Hamilton, Ont. But perhaps there would have been no reduction in AFib had it been objectively documented with the handheld ECG device, he said in an interview.

“If I were to redesign the study,” he said, “I think the primary endpoint should be confirmed atrial fibrillation, because we would have to show first that the specific trigger actually reduced objective AFib events before we then try to address the question whether reducing that trigger improves quality of life.”
 

Unrepresentative sample

The trial entered 446 overwhelmingly White and college-educated adults known to have symptomatic paroxysmal AFib who were “interested in testing a presumed AFib trigger they could readily introduce or withhold” and who owned a smartphone; the average age was 58 years, and 58% were men. The cohort was randomly assigned to the trigger-testing group or the control group, charged only with tracking their AFib.

Of the total, 320, or about 72%, completed the study; those who did not were mostly from the trigger-testing arm, leaving 136 in that group versus 184 patients in the control group.

Potential triggers that participants selected for tracking included, foremost, caffeine, alcohol, reduced sleep, and exercise, followed by lying on the left side, dehydration, large meals, and cold food or drink, the report noted.

Patients in the control group used the smartphone app and handheld ECG monitor (KardiaMobile, AliveCor) to document the duration and severity of AFib episodes daily and received data summary reports through the app weekly for 10 weeks. They then had the option to follow the trigger-testing protocol at least once.

Those in the trigger-testing group conducted their N-of-1 trials by exposing themselves to their chosen potential trigger during 3 separate weeks and avoiding the trigger during 3 other weeks, alternating each of the 6 weeks of trigger exposure or avoidance. They were instructed through the app to start the 6-week sequence with one or the other strategy randomly and to regularly track their AFib.

At the end of 6 weeks, each participant in the trigger-testing group had the opportunity to review their data for any potential trigger-AFib associations. They were then to use the next 4 weeks to enact lifestyle changes based on what they learned – as described in the report and on clinicaltrials.gov. They had the option of repeating the entire N-of-1 sequence at least one more time.

Participants in both the trigger-tracking and control arms were tested at baseline and at 10 weeks using the validated Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire.

AFEQT scores didn’t change significantly over the 10 weeks in either arm, nor were they significantly different in one arm, compared with the other.

On the other hand, patients in the trigger-tracking arm reported significantly fewer daily AFib episodes during the final 4-week period of lifestyle changes based on their N-of-1 trial results, compared to the monitoring-only control group’s final 4 weeks.

The adjusted relative risk in the trigger-tracking arm was 0.60 (95% confidence interval, 0.43-0.83; P < .001), the difference driven by patients who selected alcohol, dehydration, or exercise for their trigger, Dr. Marcus reported.

Only alcohol intake emerged consistently as a significant predictor of risk for self-reported AFib episodes in a series of meta-analyses conducted using all of the individual N-of-1 trials that provided per-protocol data. The odds ratio was 1.77 (95% CI, 1.20-2.69).

I-STOP-AFib explored an important subject “that has been understudied,” Dr. Conen said. “The trial has some limitations that the authors address themselves, but hopefully it opens the path to future studies that can build upon this experience.”

Dr. Marcus reported receiving personal fees and equity interest from InCarda Therapeutics; personal fees from Johnson & Johnson; and grants from Baylis Medical, Medtronic, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the California Tobacco-Related Disease Research Program.

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

A novel trial using real-time monitoring found that drinking coffee did not increase atrial arrhythmias but was associated with more premature ventricular contractions.

S_Bachstroem/Getty Images

There was no increase in premature atrial contractions (PACs) or supraventricular tachycardia (SVT) with coffee consumption, and, in fact, there was less SVT in per protocol analyses.

Coffee consumption was also linked to a “clinically meaningful increase in physical activity as well as a clinically meaningful reduction in sleep,” coprincipal investigator Gregory M. Marcus, MD, of the University of California, San Francisco, reported at the American Heart Association scientific sessions.

Although some professional society guidelines warn against caffeine consumption to avoid arrhythmias, he noted that the data have been mixed and that growing evidence suggests coffee consumption may actually lower the risk for arrhythmias, diabetes, and even mortality. The exact relationship has been hard to prove, however, as most coffee studies are observational and rely on self-report.

The Coffee and Real-time Atrial and Ventricular Ectopy (CRAVE) trial took advantage of digital health tools to examine the effect of caffeine consumption on cardiac ectopy burden in 100 healthy volunteers using an N-of-1 design. The primary outcomes were daily PAC and premature ventricular contraction (PVC) counts.

Participants consumed as much coffee as they wanted for 1 day and avoided all caffeine the next, alternating the assignment in 2-day blocks over 2 weeks. They used a smartphone app to receive daily coffee assignments and reminders and wore a continuous recording electrocardiography monitor (ZioPatch, iRhythm Technologies); a continuous glucose monitor (Dexcom); and Fitbit Flex 2, which recorded step counts and sleep duration.

At baseline, 21% of participants drank six to seven cups of coffee per month, 29% drank one cup per day, 21% drank two to three cups per day, and 3% drank four to five cups per day. The U.S. Food and Drug Administration has cited 400 mg per day, or about four or five cups of coffee, as generally safe for healthy adults.

To assess adherence, participants were asked to press the button on the ZioPatch for every coffee drink and were queried daily regarding actual coffee consumption the previous day. Date-stamped receipts for coffee purchases were reimbursed, and smartphone geolocation was used to track coffee shop visits. The great majority of times, participants followed their assignment by all measures, Dr. Marcus said.

ITT and per protocol analyses

ZioPatch data collected over a median of 13.3 days showed a daily median of 12.8 PACs, 7.5 PVCs, 1 nonsustained SVT, and 1 nonsustained ventricular tachycardia.

In intention-to-treat (ITT) analyses, there was no evidence of a relationship between coffee consumption and daily PAC counts (RR, 1.09; 95% confidence interval, 0.98-1.20; P = .10).

In contrast, participants had an average of 54% more PVCs on days randomized to coffee by ITT (RR, 1.54; 95% CI, 1.19-2.00; P = .001), and, per protocol, those consuming more than two cups of coffee per day had a doubling of PVCs (RR, 2.20; 95% CI, 1.24-3.92; P = .007).

No relationship was observed with coffee consumption and SVT episodes in ITT analyses (RR, 0.84; 95% CI, 0.69-1.03; P = .10), but, per protocol, every additional coffee drink consumed in real time was associated with a 12% lower risk for an SVT episode (RR, 0.88; 95% CI, 0.79-0.99; P = .028).

No significant relationships were observed with VT episodes, which were admittedly rare, Dr. Marcus said.

In ITT analyses that adjusted for day of the week, participants took an average of 1,058 more steps on days they drank coffee (95% CI, 441-1,675 steps; P = .001) but slept 36 fewer minutes (95% CI, 22-50 minutes; P < .001).

Per protocol, every additional coffee drink was associated with 587 more steps per day (95% CI, 355-820 steps; P < .001) and 18 fewer minutes of sleep (95% CI, 13-23 minutes; P < .001).

No significant differences in glucose levels were observed. Genetic analyses revealed two significant interactions: fast coffee metabolizers had a heightened risk for PVCs and slow metabolizers experienced more sleep deprivation, Dr. Marcus said.

Typical patients?

Dedicated discussant Sana Al-Khatib, MD, MHS, Duke University Medical Center, Durham, N.C., said CRAVE is a “well-conducted and informative trial” that very nicely and effectively used a digital health platform.

She pointed out, however, that the trial enrolled healthy volunteers who not only owned a smartphone but were able to interact with the study team using it. They also had an average age of 38 years, median body mass index of 24 kg/m², and no prior arrhythmias or cardiovascular issues. “These are not representative of the average patient that we see in clinical practice.”

“The other thing to keep in mind is that the primary outcome that they looked at, while relevant, is not adequate in my view to help us derive definitive conclusions about how coffee consumption affects clinically meaningful arrhythmias,” Dr. Al-Khatib said. “Yes, PACs trigger atrial fibrillation, but they don’t do so in every patient. And PVCs have been shown to be associated with increased mortality as well as worsened cardiovascular outcomes, but that’s mostly in patients with structural heart disease.”

She praised the investigators for including genetic data in their analysis. “Whether the results related to physical activity and sleep translate into any major effect on clinical outcomes deserves a study.”

The overall findings need to be replicated by other groups, in other populations, and examine hard outcomes over longer follow-up, concluded Dr. Al-Khatib.

Speaking to this news organization, Dr. Marcus countered that the participants were “pretty run of the mill” coffee drinkers of all ages and that the study highlights the complexity of coffee consumption as well as providing unique data inferring causality regarding increasing physical activity.

“Because coffee is so commonly consumed, highlighting the actual effects is important, and the hope is that understanding those true causal effects and minimizing confounding will help tailor recommendations regarding coffee consumption,” he said. “For those concerned about atrial fibrillation, for example, these data suggest that avoiding coffee does not necessarily make sense to reduce the risk of atrial fibrillation. For those with ventricular arrhythmias, abstinence or minimizing coffee may be a worthwhile experiment.”

Kalyanam Shivkumar, MD, PhD, director of the cardiac arrhythmia center at the University of California, Los Angeles, told this news organization that CRAVE is an important and much-needed study that provides reassuring and objective data for a common clinical question.

“It fits in with the emerging consensus that, in itself, coffee is not problematic,” he said. “And it provides a nice framework for what we’ll be seeing in the future – more studies that use these types of long ECG recordings and interlinking that data with biological readouts.”

Although it is too early to draw any conclusions regarding the genetic analyses, “future studies could use this as a baseline to further explore what happens between fast and slow metabolizers. This is a very useful stepping stone to putting data in context for an individual patient.”

Unless coffee consumption is excessive, such as over five cups per day in young people, all of the evidence points to coffee and caffeine being safe, Chip Lavie, MD, a frequent coffee researcher and medical director of cardiac rehabilitation and prevention at John Ochsner Heart and Vascular Institute, New Orleans, told this news organization.

“The benefits of coffee on physical activity/sleep seem to outweigh the risks as this current study suggests,” he said. “This study also supports the safety with regards to atrial arrhythmias, and suggests that those with symptomatic PVCs could try reducing coffee to see if they feel better. In total, however, the benefits of one or several cups of coffee per day on cardiovascular disease outweigh the risks.”

The study was funded by the University of California, San Francisco. Dr. Marcus reports research with the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Tobacco-Related Disease Research Program, Medtronic, Eight Sleep, and Baylis; consulting for InCarda Therapeutics and Johnson & Johnson; and equity in InCarda Therapeutics as cofounder.

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

A novel trial using real-time monitoring found that drinking coffee did not increase atrial arrhythmias but was associated with more premature ventricular contractions.

S_Bachstroem/Getty Images

There was no increase in premature atrial contractions (PACs) or supraventricular tachycardia (SVT) with coffee consumption, and, in fact, there was less SVT in per protocol analyses.

Coffee consumption was also linked to a “clinically meaningful increase in physical activity as well as a clinically meaningful reduction in sleep,” coprincipal investigator Gregory M. Marcus, MD, of the University of California, San Francisco, reported at the American Heart Association scientific sessions.

Although some professional society guidelines warn against caffeine consumption to avoid arrhythmias, he noted that the data have been mixed and that growing evidence suggests coffee consumption may actually lower the risk for arrhythmias, diabetes, and even mortality. The exact relationship has been hard to prove, however, as most coffee studies are observational and rely on self-report.

The Coffee and Real-time Atrial and Ventricular Ectopy (CRAVE) trial took advantage of digital health tools to examine the effect of caffeine consumption on cardiac ectopy burden in 100 healthy volunteers using an N-of-1 design. The primary outcomes were daily PAC and premature ventricular contraction (PVC) counts.

Participants consumed as much coffee as they wanted for 1 day and avoided all caffeine the next, alternating the assignment in 2-day blocks over 2 weeks. They used a smartphone app to receive daily coffee assignments and reminders and wore a continuous recording electrocardiography monitor (ZioPatch, iRhythm Technologies); a continuous glucose monitor (Dexcom); and Fitbit Flex 2, which recorded step counts and sleep duration.

At baseline, 21% of participants drank six to seven cups of coffee per month, 29% drank one cup per day, 21% drank two to three cups per day, and 3% drank four to five cups per day. The U.S. Food and Drug Administration has cited 400 mg per day, or about four or five cups of coffee, as generally safe for healthy adults.

To assess adherence, participants were asked to press the button on the ZioPatch for every coffee drink and were queried daily regarding actual coffee consumption the previous day. Date-stamped receipts for coffee purchases were reimbursed, and smartphone geolocation was used to track coffee shop visits. The great majority of times, participants followed their assignment by all measures, Dr. Marcus said.

ITT and per protocol analyses

ZioPatch data collected over a median of 13.3 days showed a daily median of 12.8 PACs, 7.5 PVCs, 1 nonsustained SVT, and 1 nonsustained ventricular tachycardia.

In intention-to-treat (ITT) analyses, there was no evidence of a relationship between coffee consumption and daily PAC counts (RR, 1.09; 95% confidence interval, 0.98-1.20; P = .10).

In contrast, participants had an average of 54% more PVCs on days randomized to coffee by ITT (RR, 1.54; 95% CI, 1.19-2.00; P = .001), and, per protocol, those consuming more than two cups of coffee per day had a doubling of PVCs (RR, 2.20; 95% CI, 1.24-3.92; P = .007).

No relationship was observed with coffee consumption and SVT episodes in ITT analyses (RR, 0.84; 95% CI, 0.69-1.03; P = .10), but, per protocol, every additional coffee drink consumed in real time was associated with a 12% lower risk for an SVT episode (RR, 0.88; 95% CI, 0.79-0.99; P = .028).

No significant relationships were observed with VT episodes, which were admittedly rare, Dr. Marcus said.

In ITT analyses that adjusted for day of the week, participants took an average of 1,058 more steps on days they drank coffee (95% CI, 441-1,675 steps; P = .001) but slept 36 fewer minutes (95% CI, 22-50 minutes; P < .001).

Per protocol, every additional coffee drink was associated with 587 more steps per day (95% CI, 355-820 steps; P < .001) and 18 fewer minutes of sleep (95% CI, 13-23 minutes; P < .001).

No significant differences in glucose levels were observed. Genetic analyses revealed two significant interactions: fast coffee metabolizers had a heightened risk for PVCs and slow metabolizers experienced more sleep deprivation, Dr. Marcus said.

Typical patients?

Dedicated discussant Sana Al-Khatib, MD, MHS, Duke University Medical Center, Durham, N.C., said CRAVE is a “well-conducted and informative trial” that very nicely and effectively used a digital health platform.

She pointed out, however, that the trial enrolled healthy volunteers who not only owned a smartphone but were able to interact with the study team using it. They also had an average age of 38 years, median body mass index of 24 kg/m², and no prior arrhythmias or cardiovascular issues. “These are not representative of the average patient that we see in clinical practice.”

“The other thing to keep in mind is that the primary outcome that they looked at, while relevant, is not adequate in my view to help us derive definitive conclusions about how coffee consumption affects clinically meaningful arrhythmias,” Dr. Al-Khatib said. “Yes, PACs trigger atrial fibrillation, but they don’t do so in every patient. And PVCs have been shown to be associated with increased mortality as well as worsened cardiovascular outcomes, but that’s mostly in patients with structural heart disease.”

She praised the investigators for including genetic data in their analysis. “Whether the results related to physical activity and sleep translate into any major effect on clinical outcomes deserves a study.”

The overall findings need to be replicated by other groups, in other populations, and examine hard outcomes over longer follow-up, concluded Dr. Al-Khatib.

Speaking to this news organization, Dr. Marcus countered that the participants were “pretty run of the mill” coffee drinkers of all ages and that the study highlights the complexity of coffee consumption as well as providing unique data inferring causality regarding increasing physical activity.

“Because coffee is so commonly consumed, highlighting the actual effects is important, and the hope is that understanding those true causal effects and minimizing confounding will help tailor recommendations regarding coffee consumption,” he said. “For those concerned about atrial fibrillation, for example, these data suggest that avoiding coffee does not necessarily make sense to reduce the risk of atrial fibrillation. For those with ventricular arrhythmias, abstinence or minimizing coffee may be a worthwhile experiment.”

Kalyanam Shivkumar, MD, PhD, director of the cardiac arrhythmia center at the University of California, Los Angeles, told this news organization that CRAVE is an important and much-needed study that provides reassuring and objective data for a common clinical question.

“It fits in with the emerging consensus that, in itself, coffee is not problematic,” he said. “And it provides a nice framework for what we’ll be seeing in the future – more studies that use these types of long ECG recordings and interlinking that data with biological readouts.”

Although it is too early to draw any conclusions regarding the genetic analyses, “future studies could use this as a baseline to further explore what happens between fast and slow metabolizers. This is a very useful stepping stone to putting data in context for an individual patient.”

Unless coffee consumption is excessive, such as over five cups per day in young people, all of the evidence points to coffee and caffeine being safe, Chip Lavie, MD, a frequent coffee researcher and medical director of cardiac rehabilitation and prevention at John Ochsner Heart and Vascular Institute, New Orleans, told this news organization.

“The benefits of coffee on physical activity/sleep seem to outweigh the risks as this current study suggests,” he said. “This study also supports the safety with regards to atrial arrhythmias, and suggests that those with symptomatic PVCs could try reducing coffee to see if they feel better. In total, however, the benefits of one or several cups of coffee per day on cardiovascular disease outweigh the risks.”

The study was funded by the University of California, San Francisco. Dr. Marcus reports research with the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Tobacco-Related Disease Research Program, Medtronic, Eight Sleep, and Baylis; consulting for InCarda Therapeutics and Johnson & Johnson; and equity in InCarda Therapeutics as cofounder.

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

A novel trial using real-time monitoring found that drinking coffee did not increase atrial arrhythmias but was associated with more premature ventricular contractions.

S_Bachstroem/Getty Images

There was no increase in premature atrial contractions (PACs) or supraventricular tachycardia (SVT) with coffee consumption, and, in fact, there was less SVT in per protocol analyses.

Coffee consumption was also linked to a “clinically meaningful increase in physical activity as well as a clinically meaningful reduction in sleep,” coprincipal investigator Gregory M. Marcus, MD, of the University of California, San Francisco, reported at the American Heart Association scientific sessions.

Although some professional society guidelines warn against caffeine consumption to avoid arrhythmias, he noted that the data have been mixed and that growing evidence suggests coffee consumption may actually lower the risk for arrhythmias, diabetes, and even mortality. The exact relationship has been hard to prove, however, as most coffee studies are observational and rely on self-report.

The Coffee and Real-time Atrial and Ventricular Ectopy (CRAVE) trial took advantage of digital health tools to examine the effect of caffeine consumption on cardiac ectopy burden in 100 healthy volunteers using an N-of-1 design. The primary outcomes were daily PAC and premature ventricular contraction (PVC) counts.

Participants consumed as much coffee as they wanted for 1 day and avoided all caffeine the next, alternating the assignment in 2-day blocks over 2 weeks. They used a smartphone app to receive daily coffee assignments and reminders and wore a continuous recording electrocardiography monitor (ZioPatch, iRhythm Technologies); a continuous glucose monitor (Dexcom); and Fitbit Flex 2, which recorded step counts and sleep duration.

At baseline, 21% of participants drank six to seven cups of coffee per month, 29% drank one cup per day, 21% drank two to three cups per day, and 3% drank four to five cups per day. The U.S. Food and Drug Administration has cited 400 mg per day, or about four or five cups of coffee, as generally safe for healthy adults.

To assess adherence, participants were asked to press the button on the ZioPatch for every coffee drink and were queried daily regarding actual coffee consumption the previous day. Date-stamped receipts for coffee purchases were reimbursed, and smartphone geolocation was used to track coffee shop visits. The great majority of times, participants followed their assignment by all measures, Dr. Marcus said.

ITT and per protocol analyses

ZioPatch data collected over a median of 13.3 days showed a daily median of 12.8 PACs, 7.5 PVCs, 1 nonsustained SVT, and 1 nonsustained ventricular tachycardia.

In intention-to-treat (ITT) analyses, there was no evidence of a relationship between coffee consumption and daily PAC counts (RR, 1.09; 95% confidence interval, 0.98-1.20; P = .10).

In contrast, participants had an average of 54% more PVCs on days randomized to coffee by ITT (RR, 1.54; 95% CI, 1.19-2.00; P = .001), and, per protocol, those consuming more than two cups of coffee per day had a doubling of PVCs (RR, 2.20; 95% CI, 1.24-3.92; P = .007).

No relationship was observed with coffee consumption and SVT episodes in ITT analyses (RR, 0.84; 95% CI, 0.69-1.03; P = .10), but, per protocol, every additional coffee drink consumed in real time was associated with a 12% lower risk for an SVT episode (RR, 0.88; 95% CI, 0.79-0.99; P = .028).

No significant relationships were observed with VT episodes, which were admittedly rare, Dr. Marcus said.

In ITT analyses that adjusted for day of the week, participants took an average of 1,058 more steps on days they drank coffee (95% CI, 441-1,675 steps; P = .001) but slept 36 fewer minutes (95% CI, 22-50 minutes; P < .001).

Per protocol, every additional coffee drink was associated with 587 more steps per day (95% CI, 355-820 steps; P < .001) and 18 fewer minutes of sleep (95% CI, 13-23 minutes; P < .001).

No significant differences in glucose levels were observed. Genetic analyses revealed two significant interactions: fast coffee metabolizers had a heightened risk for PVCs and slow metabolizers experienced more sleep deprivation, Dr. Marcus said.

Typical patients?

Dedicated discussant Sana Al-Khatib, MD, MHS, Duke University Medical Center, Durham, N.C., said CRAVE is a “well-conducted and informative trial” that very nicely and effectively used a digital health platform.

She pointed out, however, that the trial enrolled healthy volunteers who not only owned a smartphone but were able to interact with the study team using it. They also had an average age of 38 years, median body mass index of 24 kg/m², and no prior arrhythmias or cardiovascular issues. “These are not representative of the average patient that we see in clinical practice.”

“The other thing to keep in mind is that the primary outcome that they looked at, while relevant, is not adequate in my view to help us derive definitive conclusions about how coffee consumption affects clinically meaningful arrhythmias,” Dr. Al-Khatib said. “Yes, PACs trigger atrial fibrillation, but they don’t do so in every patient. And PVCs have been shown to be associated with increased mortality as well as worsened cardiovascular outcomes, but that’s mostly in patients with structural heart disease.”

She praised the investigators for including genetic data in their analysis. “Whether the results related to physical activity and sleep translate into any major effect on clinical outcomes deserves a study.”

The overall findings need to be replicated by other groups, in other populations, and examine hard outcomes over longer follow-up, concluded Dr. Al-Khatib.

Speaking to this news organization, Dr. Marcus countered that the participants were “pretty run of the mill” coffee drinkers of all ages and that the study highlights the complexity of coffee consumption as well as providing unique data inferring causality regarding increasing physical activity.

“Because coffee is so commonly consumed, highlighting the actual effects is important, and the hope is that understanding those true causal effects and minimizing confounding will help tailor recommendations regarding coffee consumption,” he said. “For those concerned about atrial fibrillation, for example, these data suggest that avoiding coffee does not necessarily make sense to reduce the risk of atrial fibrillation. For those with ventricular arrhythmias, abstinence or minimizing coffee may be a worthwhile experiment.”

Kalyanam Shivkumar, MD, PhD, director of the cardiac arrhythmia center at the University of California, Los Angeles, told this news organization that CRAVE is an important and much-needed study that provides reassuring and objective data for a common clinical question.

“It fits in with the emerging consensus that, in itself, coffee is not problematic,” he said. “And it provides a nice framework for what we’ll be seeing in the future – more studies that use these types of long ECG recordings and interlinking that data with biological readouts.”

Although it is too early to draw any conclusions regarding the genetic analyses, “future studies could use this as a baseline to further explore what happens between fast and slow metabolizers. This is a very useful stepping stone to putting data in context for an individual patient.”

Unless coffee consumption is excessive, such as over five cups per day in young people, all of the evidence points to coffee and caffeine being safe, Chip Lavie, MD, a frequent coffee researcher and medical director of cardiac rehabilitation and prevention at John Ochsner Heart and Vascular Institute, New Orleans, told this news organization.

“The benefits of coffee on physical activity/sleep seem to outweigh the risks as this current study suggests,” he said. “This study also supports the safety with regards to atrial arrhythmias, and suggests that those with symptomatic PVCs could try reducing coffee to see if they feel better. In total, however, the benefits of one or several cups of coffee per day on cardiovascular disease outweigh the risks.”

The study was funded by the University of California, San Francisco. Dr. Marcus reports research with the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Tobacco-Related Disease Research Program, Medtronic, Eight Sleep, and Baylis; consulting for InCarda Therapeutics and Johnson & Johnson; and equity in InCarda Therapeutics as cofounder.

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

In patients treated for persistent atrial fibrillation (AFib) with pulmonary vein antral isolation (PVAI), there was a numerical but not a statistical advantage for adjunctive left atrial appendage (LAA) ligation in a multicenter randomized trial.

SilkenOne/Thinkstock.com

The study, called aMAZE, was conducted with the LARIAT LAA (AtriCure) ligation system. AtriCure announced in August that the primary efficacy endpoint was not met; the full results were presented Nov. 14 at the American Heart Association scientific sessions.

Exploratory analyses suggested that some subgroups might benefit, but the overall 4.3% advantage provided by adjunctive LAA ligation for freedom from atrial arrhythmias (AA) at 12 months “did not meet predefined criteria for superiority,” according to coprincipal investigator David J. Wilber, MD.

Based on evidence that the LAA contributes substrate for generation of persistent AFib, the hypothesis of the study was that LAA ligation would improve on long-term rhythm control achieved with PVAI alone, which Dr. Wilber noted is currently suboptimal. The LARIAT device is deployed percutaneously into the LAA sac, where it seals off the opening to the left atrium, potentially blocking a pathway for rhythm disturbances.

The study randomized 610 patients at 53 sites in the United States in a 2:1 ratio to LARIAT LAA ligation plus PVAI or to PVAI alone. Enrollment criteria included longstanding persistent and symptomatic AFib and prior failure of ablation therapy. AA was defined as freedom from more than 30 seconds of AFib, atrial flutter, or atrial tachycardia 12 months after treatment without new or increased dosages of antiarrhythmia therapy.

The primary safety endpoint was a composite of serious adverse events within 30 days of placement of the LARIAT device. Technical success was defined as ≤1 mm (+/– 1 mm) residual communication between the LAA and the left atrium.

At 12 months, AA was achieved in 59.9% of those treated with PVAI alone and 64.3% in those who received the LARIAT ligation procedure in addition to PVAI. The P value for superiority was not significant (P = .835).

At 3.4%, the incidence of serious events at 30 days was considered reasonable, leading Dr. Wilber, director of electrophysiology at Loyola University in Chicago, to conclude that the LARIAT system “appears safe.” Overall, bleeding events requiring intervention occurred in 2.2%, cardiac structural injuries requiring surgery occurred in 0.8%, and vascular injuries requiring surgery occurred in 0.3%.

Technical success at 30 days was achieved by the study definition in 81%. If defined as a residual communication of 5 mm or less, the technical success rate was 99%.

Two groups appeared to potentially benefit in exploratory analyses. When stratified by AFib duration, there was a relative 7.5% reduction in AA for those who received LARIAT plus PVAI relative to PVAI alone. This trended towards statistical significance (P = .084), but no advantage was seen for those with longer duration of AFib.

For those with a median volume of at least133 cm³, the advantage of LARIAT for the primary endpoint was 12.4%. This also trended toward significance (P = .093). Conversely, there was a numerical disadvantage for LARIAT plus PVAI relative to PVAI alone for AA at 12 months.

While Dr. Wilber stressed that these analyses were not prespecified and require further exploration, he did conclude that strategies to build on the current success of PVAI with adjunctive strategies “may require some individualization,” taking into account patient or disease characteristics that exert an impact on risk of recurrent AA.

As an AHA-invited discussant on this trial, Usha B. Tedrow, MD, director of the clinical cardiac electrophysiology fellowship at Brigham and Women’s Hospital, Boston, reiterated that this study failed to meet its primary endpoint, but she agreed with the premise that “some subgroups may benefit.”

She identified several aspects of AFib pathophysiology involving the pulmonary vein and the LAA as well as prior studies that suggest the LAA might be a target for adjunctive therapy in patients treated with PVAI for persistent AFib. On this basis, she suggested that there might be other directions to explore before ruling out a role of the LARIAT device in all patients. For example, PVAI plus LARIAT ligation plus another adjunctive ablation intervention might be considered to add durable rhythm control.

She also said that the rigorous conduct of the aMAZE trial might have been a relative obstacle to its own success. Although she praised the meticulous design and conduct of the trial, it might have resulted in an uncommon benefit in controls that diluted the results.

“The success rate in the PVAI group in aMAZE was higher than standard ablation in previous studies looking at LAA exclusion. Could the strict protocol have played a role?” she asked.

Dr. Wilbur reports financial relationships with Abbott, Biosense Webster, Boston Scientific, and AtriCure, which provided funding for this study. Dr. Tedrow reports financial relationships with Abbott, Baylis Medical, Boston Scientific, Biosense Webster, and Thermedical.

In patients treated for persistent atrial fibrillation (AFib) with pulmonary vein antral isolation (PVAI), there was a numerical but not a statistical advantage for adjunctive left atrial appendage (LAA) ligation in a multicenter randomized trial.

SilkenOne/Thinkstock.com

The study, called aMAZE, was conducted with the LARIAT LAA (AtriCure) ligation system. AtriCure announced in August that the primary efficacy endpoint was not met; the full results were presented Nov. 14 at the American Heart Association scientific sessions.

Exploratory analyses suggested that some subgroups might benefit, but the overall 4.3% advantage provided by adjunctive LAA ligation for freedom from atrial arrhythmias (AA) at 12 months “did not meet predefined criteria for superiority,” according to coprincipal investigator David J. Wilber, MD.

Based on evidence that the LAA contributes substrate for generation of persistent AFib, the hypothesis of the study was that LAA ligation would improve on long-term rhythm control achieved with PVAI alone, which Dr. Wilber noted is currently suboptimal. The LARIAT device is deployed percutaneously into the LAA sac, where it seals off the opening to the left atrium, potentially blocking a pathway for rhythm disturbances.

The study randomized 610 patients at 53 sites in the United States in a 2:1 ratio to LARIAT LAA ligation plus PVAI or to PVAI alone. Enrollment criteria included longstanding persistent and symptomatic AFib and prior failure of ablation therapy. AA was defined as freedom from more than 30 seconds of AFib, atrial flutter, or atrial tachycardia 12 months after treatment without new or increased dosages of antiarrhythmia therapy.

The primary safety endpoint was a composite of serious adverse events within 30 days of placement of the LARIAT device. Technical success was defined as ≤1 mm (+/– 1 mm) residual communication between the LAA and the left atrium.

At 12 months, AA was achieved in 59.9% of those treated with PVAI alone and 64.3% in those who received the LARIAT ligation procedure in addition to PVAI. The P value for superiority was not significant (P = .835).

At 3.4%, the incidence of serious events at 30 days was considered reasonable, leading Dr. Wilber, director of electrophysiology at Loyola University in Chicago, to conclude that the LARIAT system “appears safe.” Overall, bleeding events requiring intervention occurred in 2.2%, cardiac structural injuries requiring surgery occurred in 0.8%, and vascular injuries requiring surgery occurred in 0.3%.

Technical success at 30 days was achieved by the study definition in 81%. If defined as a residual communication of 5 mm or less, the technical success rate was 99%.

Two groups appeared to potentially benefit in exploratory analyses. When stratified by AFib duration, there was a relative 7.5% reduction in AA for those who received LARIAT plus PVAI relative to PVAI alone. This trended towards statistical significance (P = .084), but no advantage was seen for those with longer duration of AFib.

For those with a median volume of at least133 cm³, the advantage of LARIAT for the primary endpoint was 12.4%. This also trended toward significance (P = .093). Conversely, there was a numerical disadvantage for LARIAT plus PVAI relative to PVAI alone for AA at 12 months.

While Dr. Wilber stressed that these analyses were not prespecified and require further exploration, he did conclude that strategies to build on the current success of PVAI with adjunctive strategies “may require some individualization,” taking into account patient or disease characteristics that exert an impact on risk of recurrent AA.

As an AHA-invited discussant on this trial, Usha B. Tedrow, MD, director of the clinical cardiac electrophysiology fellowship at Brigham and Women’s Hospital, Boston, reiterated that this study failed to meet its primary endpoint, but she agreed with the premise that “some subgroups may benefit.”

She identified several aspects of AFib pathophysiology involving the pulmonary vein and the LAA as well as prior studies that suggest the LAA might be a target for adjunctive therapy in patients treated with PVAI for persistent AFib. On this basis, she suggested that there might be other directions to explore before ruling out a role of the LARIAT device in all patients. For example, PVAI plus LARIAT ligation plus another adjunctive ablation intervention might be considered to add durable rhythm control.

She also said that the rigorous conduct of the aMAZE trial might have been a relative obstacle to its own success. Although she praised the meticulous design and conduct of the trial, it might have resulted in an uncommon benefit in controls that diluted the results.

“The success rate in the PVAI group in aMAZE was higher than standard ablation in previous studies looking at LAA exclusion. Could the strict protocol have played a role?” she asked.

Dr. Wilbur reports financial relationships with Abbott, Biosense Webster, Boston Scientific, and AtriCure, which provided funding for this study. Dr. Tedrow reports financial relationships with Abbott, Baylis Medical, Boston Scientific, Biosense Webster, and Thermedical.

In patients treated for persistent atrial fibrillation (AFib) with pulmonary vein antral isolation (PVAI), there was a numerical but not a statistical advantage for adjunctive left atrial appendage (LAA) ligation in a multicenter randomized trial.

SilkenOne/Thinkstock.com

The study, called aMAZE, was conducted with the LARIAT LAA (AtriCure) ligation system. AtriCure announced in August that the primary efficacy endpoint was not met; the full results were presented Nov. 14 at the American Heart Association scientific sessions.

Exploratory analyses suggested that some subgroups might benefit, but the overall 4.3% advantage provided by adjunctive LAA ligation for freedom from atrial arrhythmias (AA) at 12 months “did not meet predefined criteria for superiority,” according to coprincipal investigator David J. Wilber, MD.

Based on evidence that the LAA contributes substrate for generation of persistent AFib, the hypothesis of the study was that LAA ligation would improve on long-term rhythm control achieved with PVAI alone, which Dr. Wilber noted is currently suboptimal. The LARIAT device is deployed percutaneously into the LAA sac, where it seals off the opening to the left atrium, potentially blocking a pathway for rhythm disturbances.

The study randomized 610 patients at 53 sites in the United States in a 2:1 ratio to LARIAT LAA ligation plus PVAI or to PVAI alone. Enrollment criteria included longstanding persistent and symptomatic AFib and prior failure of ablation therapy. AA was defined as freedom from more than 30 seconds of AFib, atrial flutter, or atrial tachycardia 12 months after treatment without new or increased dosages of antiarrhythmia therapy.

The primary safety endpoint was a composite of serious adverse events within 30 days of placement of the LARIAT device. Technical success was defined as ≤1 mm (+/– 1 mm) residual communication between the LAA and the left atrium.

At 12 months, AA was achieved in 59.9% of those treated with PVAI alone and 64.3% in those who received the LARIAT ligation procedure in addition to PVAI. The P value for superiority was not significant (P = .835).

At 3.4%, the incidence of serious events at 30 days was considered reasonable, leading Dr. Wilber, director of electrophysiology at Loyola University in Chicago, to conclude that the LARIAT system “appears safe.” Overall, bleeding events requiring intervention occurred in 2.2%, cardiac structural injuries requiring surgery occurred in 0.8%, and vascular injuries requiring surgery occurred in 0.3%.

Technical success at 30 days was achieved by the study definition in 81%. If defined as a residual communication of 5 mm or less, the technical success rate was 99%.

Two groups appeared to potentially benefit in exploratory analyses. When stratified by AFib duration, there was a relative 7.5% reduction in AA for those who received LARIAT plus PVAI relative to PVAI alone. This trended towards statistical significance (P = .084), but no advantage was seen for those with longer duration of AFib.

For those with a median volume of at least133 cm³, the advantage of LARIAT for the primary endpoint was 12.4%. This also trended toward significance (P = .093). Conversely, there was a numerical disadvantage for LARIAT plus PVAI relative to PVAI alone for AA at 12 months.

While Dr. Wilber stressed that these analyses were not prespecified and require further exploration, he did conclude that strategies to build on the current success of PVAI with adjunctive strategies “may require some individualization,” taking into account patient or disease characteristics that exert an impact on risk of recurrent AA.

As an AHA-invited discussant on this trial, Usha B. Tedrow, MD, director of the clinical cardiac electrophysiology fellowship at Brigham and Women’s Hospital, Boston, reiterated that this study failed to meet its primary endpoint, but she agreed with the premise that “some subgroups may benefit.”

She identified several aspects of AFib pathophysiology involving the pulmonary vein and the LAA as well as prior studies that suggest the LAA might be a target for adjunctive therapy in patients treated with PVAI for persistent AFib. On this basis, she suggested that there might be other directions to explore before ruling out a role of the LARIAT device in all patients. For example, PVAI plus LARIAT ligation plus another adjunctive ablation intervention might be considered to add durable rhythm control.

She also said that the rigorous conduct of the aMAZE trial might have been a relative obstacle to its own success. Although she praised the meticulous design and conduct of the trial, it might have resulted in an uncommon benefit in controls that diluted the results.

“The success rate in the PVAI group in aMAZE was higher than standard ablation in previous studies looking at LAA exclusion. Could the strict protocol have played a role?” she asked.

Dr. Wilbur reports financial relationships with Abbott, Biosense Webster, Boston Scientific, and AtriCure, which provided funding for this study. Dr. Tedrow reports financial relationships with Abbott, Baylis Medical, Boston Scientific, Biosense Webster, and Thermedical.

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

Virtual platforms democratized scientific meetings during the COVID-19 pandemic but, as any meeting-goer will tell you, it’s the questions from the floor and the back-and-forth of an expert panel that often reveal the importance of and/or problems with a presentation. It’s the scrutiny that makes the science resonate, especially in this postfactual era.

The all-virtual American Heart Association Scientific Sessions 2021 is looking to recreate the engagement of an in-person meeting by offering more live interactive events. They range from seven late-breaking science (LBS) sessions to Saturday’s fireside chat on the Pfizer and Moderna COVID-19 vaccines and Monday’s dive into the controversial new AHA/American College of Cardiology Chest Pain guidelines.

To help digest the latest science, attendees will be able to have their questions answered in real-time via Slido, meet with the trialists, and hear live commentary from key opinion leaders after the live events. A networking function will also allow attendees and exhibitors to chat or meet virtually.

“In this day and age, many people pretty quickly can get access to the science but it’s what I call the IC sort of phenomenon – the presentation of the information, the context of the information, putting it into how I’m going to use it in my practice, and then the critical appraisal – that’s what most people want at the Scientific Sessions,” program committee chair Manesh R. Patel, MD, of Duke University School of Medicine, said in an interview. “We’re all craving ways in which we can interact with one another to put things in context.”

Plans for a hybrid in-person meeting in Boston were scuttled in September because of the Delta variant surge, but the theme of the meeting remained: “One World. Together for Science.” Attendees will be able to access more than 500 live and on-demand sessions including 117 oral abstracts, 286 poster sessions, 59 moderated digital posters, and over a dozen sessions focused on strategies to promote health equity.

“Last year there was a Presidential Session and a statement on structural racism, so we wanted to take the next step and say, What are the ways in which people are starting to interact and do things to make a difference?” explained Dr. Patel. “So, this year, you’ll see different versions of that from the Main Event session, which has some case vignettes and a panel discussion, to other health equity sessions that describe not just COVID care, but blood pressure care, maternal-fetal medicine, and congenital kids. Wherever we can, we’ve tried to infuse it throughout the sessions and will continue to.”

Late-breaking science

The LBS sessions kick off at 9:30 a.m. ET Saturday with AVATAR, a randomized trial of aortic valve replacement vs. watchful waiting in severe aortic stenosis proved asymptomatic through exercise testing.

“The findings of that trial, depending on what they are, could certainly impact clinical practice because it’s a very common scenario in which we have elderly patients with aortic valve stenosis that might be severe but they may not be symptomatic,” he said.

It’s followed by a randomized trial from the Cardiothoracic Surgical Trials Network, examining whether tricuspid repair at the time of mitral valve surgery leads to beneficial outcomes. “I think it’s a pretty important study,” Dr. Patel said, “because it’ll again affect how we think about our clinical practice.”

Rounding out the LBS.01 session is RAPID CABG, comparing early vs. delayed coronary bypass graft surgery (CABG) in patients with acute coronary syndromes on ticagrelor, and the pivotal U.S. VEST trial of an external support device already approved in Europe for saphenous vein grafts during CABG.

Saturday’s LBS.02 at 3:00 p.m. ET is devoted to hypertension and looks at how the COVID-19 pandemic affected blood pressure control. There’s also a study of remotely delivered hypertension and lipid management in 10,000 patients across the Partners Healthcare System and a cluster randomized trial of a village doctor–led blood pressure intervention in rural China.

Sunday’s LBS.03 at 8:00 a.m. ET is focused on atrial arrhythmias, starting with the CRAVE trial examining the effect of caffeine consumption on cardiac ectopy burden in 108 patients using an N-of-1 design and 2-day blocks on and off caffeine. “There’s an ability to identify a dose response that you get arrhythmias when you increase the amount of coffee you drink vs. not in an individual, so I think that will be likely discussed a lot and worth paying attention to,” Dr. Patel said.

The session also includes GIRAF, a comparison of cognitive outcomes with dabigatran (Pradaxa) vs. warfarin (Coumadin) in nonvalvular atrial fibrillation (AF); PALACS, a randomized trial examining whether left-sided pericardiotomy prevents AF after cardiac surgery; and AMAZE, which study sponsor AtriCure revealed missed its primary efficacy endpoint of freedom from AF with the LARIAT suture delivery device for left atrial appendage closure plus pulmonary vein isolation.

LBS.04 at 3:30 p.m. ET Sunday takes on digital health, with results from the nonrandomized Fitbit Heart Study on AF notifications from 450,000 participants wearing a single-lead ECG patch. “A lot of technologies claim that they can detect things, and we should ask that people go through the rigorous evaluation to see if they in fact do. So, in that respect, I think it›s an important step,” observed Dr. Patel.

Also on tap is I-STOP-AFib, another N-of-1 study using mobile apps and the AliveCor device to identify individual AF triggers; and REVeAL-HF, a 4,000-patient study examining whether electronic alerts that provide clinicians with prognostic information on their heart failure (HF) patients will reduce mortality and 30-day HF hospitalizations.

LBS.05 at 5:00 p.m. ET provides new information from EMPEROR-Preserved in HF with preserved ejection fraction and main results from EMPULSE, also using the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in 530 patients hospitalized for acute HF.

The session also features CHIEF-HF, a randomized trial leveraging mobile technologies to test whether 12 weeks of another SGLT2 inhibitor, canagliflozin (Invokana), is superior to placebo for improving HF symptoms; and DREAM-HF, a comparison of transendocardial delivery of allogeneic mesenchymal precursor cells vs. a sham comparator in chronic HF as a result of left ventricular systolic dysfunction.

Monday’s LBS.06 at 8:00 a.m. ET details the safety and cholesterol-lowering efficacy of MK-0616, an investigational oral PCSK9 inhibitor. “It’s just a phase 2 [trial], but there’s interest in an oral PCSK9 inhibitor, given that the current ones are subcutaneous,” Dr. Patel said.

Results will also be presented from PREPARE-IT 2, which tested icosapent ethyl vs. placebo in outpatients with COVID-19. In the recently reported PREPARE-IT 1, a loading dose of icosapent ethyl failed to reduce the risk of hospitalization with SARS-CoV-2 infection among at-risk individuals.

LBS.07 at 11:00 a.m. Monday completes the late-breakers with new results from ASCEND, this time examining the effect of aspirin on dementia and cognitive impairment in patients with diabetes.

Next up is a look at the effectiveness of P2Y12 inhibitors in hospitalized patients with COVID-19 in the adaptive ACTIV-4a trial, followed by results of the pivotal phase 3 REVERSE-IT trial of bentracimab, a recombinant human monoclonal antibody antigen fragment designed to reverse the antiplatelet activity of ticagrelor in the event of major bleeding or when urgent surgery is needed.

Closing out the session is AXIOMATIC-TKR, a double-blind comparison of the safety and efficacy of the investigational oral factor XI anticoagulant JNJ-70033093 vs. subcutaneous enoxaparin (Lovenox) in elective total knee replacement.

For those searching for more AHA-related science online, the Resuscitation Science Symposium (ReSS) will run from this Friday through Sunday and the Quality of Care and Outcomes Research (QCOR) Scientific Sessions will take the stage next Monday, Nov. 15.

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

Virtual platforms democratized scientific meetings during the COVID-19 pandemic but, as any meeting-goer will tell you, it’s the questions from the floor and the back-and-forth of an expert panel that often reveal the importance of and/or problems with a presentation. It’s the scrutiny that makes the science resonate, especially in this postfactual era.

The all-virtual American Heart Association Scientific Sessions 2021 is looking to recreate the engagement of an in-person meeting by offering more live interactive events. They range from seven late-breaking science (LBS) sessions to Saturday’s fireside chat on the Pfizer and Moderna COVID-19 vaccines and Monday’s dive into the controversial new AHA/American College of Cardiology Chest Pain guidelines.

To help digest the latest science, attendees will be able to have their questions answered in real-time via Slido, meet with the trialists, and hear live commentary from key opinion leaders after the live events. A networking function will also allow attendees and exhibitors to chat or meet virtually.

“In this day and age, many people pretty quickly can get access to the science but it’s what I call the IC sort of phenomenon – the presentation of the information, the context of the information, putting it into how I’m going to use it in my practice, and then the critical appraisal – that’s what most people want at the Scientific Sessions,” program committee chair Manesh R. Patel, MD, of Duke University School of Medicine, said in an interview. “We’re all craving ways in which we can interact with one another to put things in context.”

Plans for a hybrid in-person meeting in Boston were scuttled in September because of the Delta variant surge, but the theme of the meeting remained: “One World. Together for Science.” Attendees will be able to access more than 500 live and on-demand sessions including 117 oral abstracts, 286 poster sessions, 59 moderated digital posters, and over a dozen sessions focused on strategies to promote health equity.

“Last year there was a Presidential Session and a statement on structural racism, so we wanted to take the next step and say, What are the ways in which people are starting to interact and do things to make a difference?” explained Dr. Patel. “So, this year, you’ll see different versions of that from the Main Event session, which has some case vignettes and a panel discussion, to other health equity sessions that describe not just COVID care, but blood pressure care, maternal-fetal medicine, and congenital kids. Wherever we can, we’ve tried to infuse it throughout the sessions and will continue to.”

Late-breaking science

The LBS sessions kick off at 9:30 a.m. ET Saturday with AVATAR, a randomized trial of aortic valve replacement vs. watchful waiting in severe aortic stenosis proved asymptomatic through exercise testing.

“The findings of that trial, depending on what they are, could certainly impact clinical practice because it’s a very common scenario in which we have elderly patients with aortic valve stenosis that might be severe but they may not be symptomatic,” he said.

It’s followed by a randomized trial from the Cardiothoracic Surgical Trials Network, examining whether tricuspid repair at the time of mitral valve surgery leads to beneficial outcomes. “I think it’s a pretty important study,” Dr. Patel said, “because it’ll again affect how we think about our clinical practice.”

Rounding out the LBS.01 session is RAPID CABG, comparing early vs. delayed coronary bypass graft surgery (CABG) in patients with acute coronary syndromes on ticagrelor, and the pivotal U.S. VEST trial of an external support device already approved in Europe for saphenous vein grafts during CABG.

Saturday’s LBS.02 at 3:00 p.m. ET is devoted to hypertension and looks at how the COVID-19 pandemic affected blood pressure control. There’s also a study of remotely delivered hypertension and lipid management in 10,000 patients across the Partners Healthcare System and a cluster randomized trial of a village doctor–led blood pressure intervention in rural China.

Sunday’s LBS.03 at 8:00 a.m. ET is focused on atrial arrhythmias, starting with the CRAVE trial examining the effect of caffeine consumption on cardiac ectopy burden in 108 patients using an N-of-1 design and 2-day blocks on and off caffeine. “There’s an ability to identify a dose response that you get arrhythmias when you increase the amount of coffee you drink vs. not in an individual, so I think that will be likely discussed a lot and worth paying attention to,” Dr. Patel said.

The session also includes GIRAF, a comparison of cognitive outcomes with dabigatran (Pradaxa) vs. warfarin (Coumadin) in nonvalvular atrial fibrillation (AF); PALACS, a randomized trial examining whether left-sided pericardiotomy prevents AF after cardiac surgery; and AMAZE, which study sponsor AtriCure revealed missed its primary efficacy endpoint of freedom from AF with the LARIAT suture delivery device for left atrial appendage closure plus pulmonary vein isolation.

LBS.04 at 3:30 p.m. ET Sunday takes on digital health, with results from the nonrandomized Fitbit Heart Study on AF notifications from 450,000 participants wearing a single-lead ECG patch. “A lot of technologies claim that they can detect things, and we should ask that people go through the rigorous evaluation to see if they in fact do. So, in that respect, I think it›s an important step,” observed Dr. Patel.

Also on tap is I-STOP-AFib, another N-of-1 study using mobile apps and the AliveCor device to identify individual AF triggers; and REVeAL-HF, a 4,000-patient study examining whether electronic alerts that provide clinicians with prognostic information on their heart failure (HF) patients will reduce mortality and 30-day HF hospitalizations.

LBS.05 at 5:00 p.m. ET provides new information from EMPEROR-Preserved in HF with preserved ejection fraction and main results from EMPULSE, also using the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in 530 patients hospitalized for acute HF.

The session also features CHIEF-HF, a randomized trial leveraging mobile technologies to test whether 12 weeks of another SGLT2 inhibitor, canagliflozin (Invokana), is superior to placebo for improving HF symptoms; and DREAM-HF, a comparison of transendocardial delivery of allogeneic mesenchymal precursor cells vs. a sham comparator in chronic HF as a result of left ventricular systolic dysfunction.

Monday’s LBS.06 at 8:00 a.m. ET details the safety and cholesterol-lowering efficacy of MK-0616, an investigational oral PCSK9 inhibitor. “It’s just a phase 2 [trial], but there’s interest in an oral PCSK9 inhibitor, given that the current ones are subcutaneous,” Dr. Patel said.

Results will also be presented from PREPARE-IT 2, which tested icosapent ethyl vs. placebo in outpatients with COVID-19. In the recently reported PREPARE-IT 1, a loading dose of icosapent ethyl failed to reduce the risk of hospitalization with SARS-CoV-2 infection among at-risk individuals.

LBS.07 at 11:00 a.m. Monday completes the late-breakers with new results from ASCEND, this time examining the effect of aspirin on dementia and cognitive impairment in patients with diabetes.

Next up is a look at the effectiveness of P2Y12 inhibitors in hospitalized patients with COVID-19 in the adaptive ACTIV-4a trial, followed by results of the pivotal phase 3 REVERSE-IT trial of bentracimab, a recombinant human monoclonal antibody antigen fragment designed to reverse the antiplatelet activity of ticagrelor in the event of major bleeding or when urgent surgery is needed.

Closing out the session is AXIOMATIC-TKR, a double-blind comparison of the safety and efficacy of the investigational oral factor XI anticoagulant JNJ-70033093 vs. subcutaneous enoxaparin (Lovenox) in elective total knee replacement.

For those searching for more AHA-related science online, the Resuscitation Science Symposium (ReSS) will run from this Friday through Sunday and the Quality of Care and Outcomes Research (QCOR) Scientific Sessions will take the stage next Monday, Nov. 15.

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

Virtual platforms democratized scientific meetings during the COVID-19 pandemic but, as any meeting-goer will tell you, it’s the questions from the floor and the back-and-forth of an expert panel that often reveal the importance of and/or problems with a presentation. It’s the scrutiny that makes the science resonate, especially in this postfactual era.

The all-virtual American Heart Association Scientific Sessions 2021 is looking to recreate the engagement of an in-person meeting by offering more live interactive events. They range from seven late-breaking science (LBS) sessions to Saturday’s fireside chat on the Pfizer and Moderna COVID-19 vaccines and Monday’s dive into the controversial new AHA/American College of Cardiology Chest Pain guidelines.

To help digest the latest science, attendees will be able to have their questions answered in real-time via Slido, meet with the trialists, and hear live commentary from key opinion leaders after the live events. A networking function will also allow attendees and exhibitors to chat or meet virtually.

“In this day and age, many people pretty quickly can get access to the science but it’s what I call the IC sort of phenomenon – the presentation of the information, the context of the information, putting it into how I’m going to use it in my practice, and then the critical appraisal – that’s what most people want at the Scientific Sessions,” program committee chair Manesh R. Patel, MD, of Duke University School of Medicine, said in an interview. “We’re all craving ways in which we can interact with one another to put things in context.”

Plans for a hybrid in-person meeting in Boston were scuttled in September because of the Delta variant surge, but the theme of the meeting remained: “One World. Together for Science.” Attendees will be able to access more than 500 live and on-demand sessions including 117 oral abstracts, 286 poster sessions, 59 moderated digital posters, and over a dozen sessions focused on strategies to promote health equity.

“Last year there was a Presidential Session and a statement on structural racism, so we wanted to take the next step and say, What are the ways in which people are starting to interact and do things to make a difference?” explained Dr. Patel. “So, this year, you’ll see different versions of that from the Main Event session, which has some case vignettes and a panel discussion, to other health equity sessions that describe not just COVID care, but blood pressure care, maternal-fetal medicine, and congenital kids. Wherever we can, we’ve tried to infuse it throughout the sessions and will continue to.”

Late-breaking science

The LBS sessions kick off at 9:30 a.m. ET Saturday with AVATAR, a randomized trial of aortic valve replacement vs. watchful waiting in severe aortic stenosis proved asymptomatic through exercise testing.

“The findings of that trial, depending on what they are, could certainly impact clinical practice because it’s a very common scenario in which we have elderly patients with aortic valve stenosis that might be severe but they may not be symptomatic,” he said.

It’s followed by a randomized trial from the Cardiothoracic Surgical Trials Network, examining whether tricuspid repair at the time of mitral valve surgery leads to beneficial outcomes. “I think it’s a pretty important study,” Dr. Patel said, “because it’ll again affect how we think about our clinical practice.”

Rounding out the LBS.01 session is RAPID CABG, comparing early vs. delayed coronary bypass graft surgery (CABG) in patients with acute coronary syndromes on ticagrelor, and the pivotal U.S. VEST trial of an external support device already approved in Europe for saphenous vein grafts during CABG.

Saturday’s LBS.02 at 3:00 p.m. ET is devoted to hypertension and looks at how the COVID-19 pandemic affected blood pressure control. There’s also a study of remotely delivered hypertension and lipid management in 10,000 patients across the Partners Healthcare System and a cluster randomized trial of a village doctor–led blood pressure intervention in rural China.

Sunday’s LBS.03 at 8:00 a.m. ET is focused on atrial arrhythmias, starting with the CRAVE trial examining the effect of caffeine consumption on cardiac ectopy burden in 108 patients using an N-of-1 design and 2-day blocks on and off caffeine. “There’s an ability to identify a dose response that you get arrhythmias when you increase the amount of coffee you drink vs. not in an individual, so I think that will be likely discussed a lot and worth paying attention to,” Dr. Patel said.

The session also includes GIRAF, a comparison of cognitive outcomes with dabigatran (Pradaxa) vs. warfarin (Coumadin) in nonvalvular atrial fibrillation (AF); PALACS, a randomized trial examining whether left-sided pericardiotomy prevents AF after cardiac surgery; and AMAZE, which study sponsor AtriCure revealed missed its primary efficacy endpoint of freedom from AF with the LARIAT suture delivery device for left atrial appendage closure plus pulmonary vein isolation.

LBS.04 at 3:30 p.m. ET Sunday takes on digital health, with results from the nonrandomized Fitbit Heart Study on AF notifications from 450,000 participants wearing a single-lead ECG patch. “A lot of technologies claim that they can detect things, and we should ask that people go through the rigorous evaluation to see if they in fact do. So, in that respect, I think it›s an important step,” observed Dr. Patel.

Also on tap is I-STOP-AFib, another N-of-1 study using mobile apps and the AliveCor device to identify individual AF triggers; and REVeAL-HF, a 4,000-patient study examining whether electronic alerts that provide clinicians with prognostic information on their heart failure (HF) patients will reduce mortality and 30-day HF hospitalizations.

LBS.05 at 5:00 p.m. ET provides new information from EMPEROR-Preserved in HF with preserved ejection fraction and main results from EMPULSE, also using the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in 530 patients hospitalized for acute HF.

The session also features CHIEF-HF, a randomized trial leveraging mobile technologies to test whether 12 weeks of another SGLT2 inhibitor, canagliflozin (Invokana), is superior to placebo for improving HF symptoms; and DREAM-HF, a comparison of transendocardial delivery of allogeneic mesenchymal precursor cells vs. a sham comparator in chronic HF as a result of left ventricular systolic dysfunction.

Monday’s LBS.06 at 8:00 a.m. ET details the safety and cholesterol-lowering efficacy of MK-0616, an investigational oral PCSK9 inhibitor. “It’s just a phase 2 [trial], but there’s interest in an oral PCSK9 inhibitor, given that the current ones are subcutaneous,” Dr. Patel said.

Results will also be presented from PREPARE-IT 2, which tested icosapent ethyl vs. placebo in outpatients with COVID-19. In the recently reported PREPARE-IT 1, a loading dose of icosapent ethyl failed to reduce the risk of hospitalization with SARS-CoV-2 infection among at-risk individuals.

LBS.07 at 11:00 a.m. Monday completes the late-breakers with new results from ASCEND, this time examining the effect of aspirin on dementia and cognitive impairment in patients with diabetes.

Next up is a look at the effectiveness of P2Y12 inhibitors in hospitalized patients with COVID-19 in the adaptive ACTIV-4a trial, followed by results of the pivotal phase 3 REVERSE-IT trial of bentracimab, a recombinant human monoclonal antibody antigen fragment designed to reverse the antiplatelet activity of ticagrelor in the event of major bleeding or when urgent surgery is needed.

Closing out the session is AXIOMATIC-TKR, a double-blind comparison of the safety and efficacy of the investigational oral factor XI anticoagulant JNJ-70033093 vs. subcutaneous enoxaparin (Lovenox) in elective total knee replacement.

For those searching for more AHA-related science online, the Resuscitation Science Symposium (ReSS) will run from this Friday through Sunday and the Quality of Care and Outcomes Research (QCOR) Scientific Sessions will take the stage next Monday, Nov. 15.

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

Increased mental health needs, higher acuity from delayed appointments, and added questions and conversations surrounding COVID-19 are forcing primary care offices to rethink priorities in office visits.

Evidence of this came from the latest Primary Care Collaborative (PCC) survey, which found that primary care clinicians are seeing more complex patients requiring longer appointments in the wake of COVID-19.

The PCC with the Larry A. Green Center regularly surveys primary care clinicians. This round of questions came August 14-17 and included 1,263 respondents from 49 states, the District of Columbia, and two territories.

More than 7 in 10 (71%) respondents said their patients are more complex and nearly the same percentage said appointments are taking more time.

Ann Greiner, president and CEO of the PCC, said in an interview that 55% of respondents reported that clinicians are struggling to keep up with pent-up demand after patients have delayed or canceled care. Sixty-five percent in the survey said they had seen a rise in children’s mental health issues, and 58% said they were unsure how to help their patients with long COVID.

In addition, primary care clinicians are having repeated conversations with patients on why they should get a vaccine and which one.

“I think that’s adding to the complexity. There is a lot going on here with patient trust,” Ms. Greiner said.
 

‘We’re going to be playing catch-up’

Jacqueline Fincher, MD, an internist in Thompson, Ga., said in an interview that appointments have gotten longer and more complex in the wake of the pandemic – “no question.”

The immediate past president of the American College of Physicians is seeing patients with chronic disease that has gone untreated for sometimes a year or more, she said.

“Their blood pressure was not under good control, they were under more stress, their sugars were up and weren’t being followed as closely for conditions such as congestive heart failure,” she said.

Dr. Fincher, who works in a rural practice 40 miles from Augusta, Ga., with her physician husband and two other physicians, said patients are ready to come back in, “but I don’t have enough slots for them.”

She said she prioritizes what to help patients with first and schedules the next tier for the next appointment, but added, “honestly, over the next 2 years we’re going to be playing catch-up.”

At the same time, the CDC has estimated that 45% of U.S. adults are at increased risk for complications from COVID-19 because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. Rates ranged from 19.8% for people 18-29 years old to 80.7% for people over 80 years of age.
 

Long COVID could overwhelm existing health care capacity

Primary care physicians are also having to diagnose sometimes “invisible” symptoms after people have recovered from acute COVID-19 infection. Diagnosing takes intent listening to patients who describe symptoms that tests can’t confirm.

As this news organization has previously reported, half of COVID-19 survivors report postacute sequelae of COVID-19 (PASC) lasting longer than 6 months.

“These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries,” the authors wrote.
 

Anxiety, depression ‘have gone off the charts’

Danielle Loeb, MD, MPH, associate professor of internal medicine at the University of Colorado in Denver, who studies complexity in primary care, said in the wake of COVID-19, more patients have developed “new, serious anxiety.”

Courtesy Dr. Danielle Loeb

“That got extremely exacerbated during the pandemic. Anxiety and depression have gone off the charts,” said Dr. Loeb, who prefers the pronoun “they.”

Dr. Loeb cares for a large number of transgender patients. As offices reopen, some patients are having trouble reintegrating into the workplace and resuming social contacts. The primary care doctor says appointments can get longer because of the need to complete tasks, such as filling out forms for Family Medical Leave Act for those not yet ready to return to work.

COVID-19–related fears are keeping many patients from coming into the office, Dr. Loeb said, either from fear of exposure or because they have mental health issues that keep them from feeling safe leaving the house.

“That really affects my ability to care for them,” they said.

Loss of employment in the pandemic or fear of job loss and subsequent changing of insurance has complicated primary care in terms of treatment and administrative tasks, according to Dr. Loeb.

To help treat patients with acute mental health issues and manage other patients, Dr. Loeb’s practice has brought in a social worker and a therapist.

Team-based care is key in the survival of primary care practices, though providing that is difficult in the smaller clinics because of the critical mass of patients needed to make it viable, they said.

“It’s the only answer. It’s the only way you don’t drown,” Dr. Loeb added. “I’m not drowning, and I credit that to my clinic having the help to support the mental health piece of things.”
 

Rethinking workflow

Tricia McGinnis, MPP, MPH, executive vice president of the nonprofit Center for Health Care Strategies (CHCS) says complexity has forced rethinking workflow.

“A lot of the trends we’re seeing in primary care were there pre-COVID, but COVID has exacerbated those trends,” she said in an interview.

“The good news ... is that it was already becoming clear that primary care needed to provide basic mental health services and integrate with behavioral health. It had also become clear that effective primary care needed to address social issues that keep patients from accessing health care,” she said.

Expanding care teams, as Dr. Loeb mentioned, is a key strategy, according to Ms. McGinnis. Potential teams would include the clinical staff, but also social workers and community health workers – people who come from the community primary care is serving who can help build trust with patients and connect the patient to the primary care team.

“There’s a lot that needs to happen that the clinician doesn’t need to do,” she said.

Telehealth can be a big factor in coordinating the team, Ms. McGinnis added.

“It’s thinking less about who’s doing the work, but more about the work that needs to be done to keep people healthy. Then let’s think about the type of workers best suited to perform those tasks,” she said.

As for reimbursing more complex care, population-based, up-front capitated payments linked to high-quality care and better outcomes will need to replace fee-for-service models, according to Ms. McGinnis.

That will provide reliable incomes for primary care offices, but also flexibility in how each patient with different levels of complexity is managed, she said.

Ms. Greiner, Dr. Fincher, Dr. Loeb, and Ms. McGinnis have no relevant financial relationships.

Increased mental health needs, higher acuity from delayed appointments, and added questions and conversations surrounding COVID-19 are forcing primary care offices to rethink priorities in office visits.

Evidence of this came from the latest Primary Care Collaborative (PCC) survey, which found that primary care clinicians are seeing more complex patients requiring longer appointments in the wake of COVID-19.

The PCC with the Larry A. Green Center regularly surveys primary care clinicians. This round of questions came August 14-17 and included 1,263 respondents from 49 states, the District of Columbia, and two territories.

More than 7 in 10 (71%) respondents said their patients are more complex and nearly the same percentage said appointments are taking more time.

Ann Greiner, president and CEO of the PCC, said in an interview that 55% of respondents reported that clinicians are struggling to keep up with pent-up demand after patients have delayed or canceled care. Sixty-five percent in the survey said they had seen a rise in children’s mental health issues, and 58% said they were unsure how to help their patients with long COVID.

In addition, primary care clinicians are having repeated conversations with patients on why they should get a vaccine and which one.

“I think that’s adding to the complexity. There is a lot going on here with patient trust,” Ms. Greiner said.
 

‘We’re going to be playing catch-up’

Jacqueline Fincher, MD, an internist in Thompson, Ga., said in an interview that appointments have gotten longer and more complex in the wake of the pandemic – “no question.”

The immediate past president of the American College of Physicians is seeing patients with chronic disease that has gone untreated for sometimes a year or more, she said.

“Their blood pressure was not under good control, they were under more stress, their sugars were up and weren’t being followed as closely for conditions such as congestive heart failure,” she said.

Dr. Fincher, who works in a rural practice 40 miles from Augusta, Ga., with her physician husband and two other physicians, said patients are ready to come back in, “but I don’t have enough slots for them.”

She said she prioritizes what to help patients with first and schedules the next tier for the next appointment, but added, “honestly, over the next 2 years we’re going to be playing catch-up.”

At the same time, the CDC has estimated that 45% of U.S. adults are at increased risk for complications from COVID-19 because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. Rates ranged from 19.8% for people 18-29 years old to 80.7% for people over 80 years of age.
 

Long COVID could overwhelm existing health care capacity

Primary care physicians are also having to diagnose sometimes “invisible” symptoms after people have recovered from acute COVID-19 infection. Diagnosing takes intent listening to patients who describe symptoms that tests can’t confirm.

As this news organization has previously reported, half of COVID-19 survivors report postacute sequelae of COVID-19 (PASC) lasting longer than 6 months.

“These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries,” the authors wrote.
 

Anxiety, depression ‘have gone off the charts’

Danielle Loeb, MD, MPH, associate professor of internal medicine at the University of Colorado in Denver, who studies complexity in primary care, said in the wake of COVID-19, more patients have developed “new, serious anxiety.”

Courtesy Dr. Danielle Loeb

“That got extremely exacerbated during the pandemic. Anxiety and depression have gone off the charts,” said Dr. Loeb, who prefers the pronoun “they.”

Dr. Loeb cares for a large number of transgender patients. As offices reopen, some patients are having trouble reintegrating into the workplace and resuming social contacts. The primary care doctor says appointments can get longer because of the need to complete tasks, such as filling out forms for Family Medical Leave Act for those not yet ready to return to work.

COVID-19–related fears are keeping many patients from coming into the office, Dr. Loeb said, either from fear of exposure or because they have mental health issues that keep them from feeling safe leaving the house.

“That really affects my ability to care for them,” they said.

Loss of employment in the pandemic or fear of job loss and subsequent changing of insurance has complicated primary care in terms of treatment and administrative tasks, according to Dr. Loeb.

To help treat patients with acute mental health issues and manage other patients, Dr. Loeb’s practice has brought in a social worker and a therapist.

Team-based care is key in the survival of primary care practices, though providing that is difficult in the smaller clinics because of the critical mass of patients needed to make it viable, they said.

“It’s the only answer. It’s the only way you don’t drown,” Dr. Loeb added. “I’m not drowning, and I credit that to my clinic having the help to support the mental health piece of things.”
 

Rethinking workflow

Tricia McGinnis, MPP, MPH, executive vice president of the nonprofit Center for Health Care Strategies (CHCS) says complexity has forced rethinking workflow.

“A lot of the trends we’re seeing in primary care were there pre-COVID, but COVID has exacerbated those trends,” she said in an interview.

“The good news ... is that it was already becoming clear that primary care needed to provide basic mental health services and integrate with behavioral health. It had also become clear that effective primary care needed to address social issues that keep patients from accessing health care,” she said.

Expanding care teams, as Dr. Loeb mentioned, is a key strategy, according to Ms. McGinnis. Potential teams would include the clinical staff, but also social workers and community health workers – people who come from the community primary care is serving who can help build trust with patients and connect the patient to the primary care team.

“There’s a lot that needs to happen that the clinician doesn’t need to do,” she said.

Telehealth can be a big factor in coordinating the team, Ms. McGinnis added.

“It’s thinking less about who’s doing the work, but more about the work that needs to be done to keep people healthy. Then let’s think about the type of workers best suited to perform those tasks,” she said.

As for reimbursing more complex care, population-based, up-front capitated payments linked to high-quality care and better outcomes will need to replace fee-for-service models, according to Ms. McGinnis.

That will provide reliable incomes for primary care offices, but also flexibility in how each patient with different levels of complexity is managed, she said.

Ms. Greiner, Dr. Fincher, Dr. Loeb, and Ms. McGinnis have no relevant financial relationships.

Increased mental health needs, higher acuity from delayed appointments, and added questions and conversations surrounding COVID-19 are forcing primary care offices to rethink priorities in office visits.

Evidence of this came from the latest Primary Care Collaborative (PCC) survey, which found that primary care clinicians are seeing more complex patients requiring longer appointments in the wake of COVID-19.

The PCC with the Larry A. Green Center regularly surveys primary care clinicians. This round of questions came August 14-17 and included 1,263 respondents from 49 states, the District of Columbia, and two territories.

More than 7 in 10 (71%) respondents said their patients are more complex and nearly the same percentage said appointments are taking more time.

Ann Greiner, president and CEO of the PCC, said in an interview that 55% of respondents reported that clinicians are struggling to keep up with pent-up demand after patients have delayed or canceled care. Sixty-five percent in the survey said they had seen a rise in children’s mental health issues, and 58% said they were unsure how to help their patients with long COVID.

In addition, primary care clinicians are having repeated conversations with patients on why they should get a vaccine and which one.

“I think that’s adding to the complexity. There is a lot going on here with patient trust,” Ms. Greiner said.
 

‘We’re going to be playing catch-up’

Jacqueline Fincher, MD, an internist in Thompson, Ga., said in an interview that appointments have gotten longer and more complex in the wake of the pandemic – “no question.”

The immediate past president of the American College of Physicians is seeing patients with chronic disease that has gone untreated for sometimes a year or more, she said.

“Their blood pressure was not under good control, they were under more stress, their sugars were up and weren’t being followed as closely for conditions such as congestive heart failure,” she said.

Dr. Fincher, who works in a rural practice 40 miles from Augusta, Ga., with her physician husband and two other physicians, said patients are ready to come back in, “but I don’t have enough slots for them.”

She said she prioritizes what to help patients with first and schedules the next tier for the next appointment, but added, “honestly, over the next 2 years we’re going to be playing catch-up.”

At the same time, the CDC has estimated that 45% of U.S. adults are at increased risk for complications from COVID-19 because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. Rates ranged from 19.8% for people 18-29 years old to 80.7% for people over 80 years of age.
 

Long COVID could overwhelm existing health care capacity

Primary care physicians are also having to diagnose sometimes “invisible” symptoms after people have recovered from acute COVID-19 infection. Diagnosing takes intent listening to patients who describe symptoms that tests can’t confirm.

As this news organization has previously reported, half of COVID-19 survivors report postacute sequelae of COVID-19 (PASC) lasting longer than 6 months.

“These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries,” the authors wrote.
 

Anxiety, depression ‘have gone off the charts’

Danielle Loeb, MD, MPH, associate professor of internal medicine at the University of Colorado in Denver, who studies complexity in primary care, said in the wake of COVID-19, more patients have developed “new, serious anxiety.”

Courtesy Dr. Danielle Loeb

“That got extremely exacerbated during the pandemic. Anxiety and depression have gone off the charts,” said Dr. Loeb, who prefers the pronoun “they.”

Dr. Loeb cares for a large number of transgender patients. As offices reopen, some patients are having trouble reintegrating into the workplace and resuming social contacts. The primary care doctor says appointments can get longer because of the need to complete tasks, such as filling out forms for Family Medical Leave Act for those not yet ready to return to work.

COVID-19–related fears are keeping many patients from coming into the office, Dr. Loeb said, either from fear of exposure or because they have mental health issues that keep them from feeling safe leaving the house.

“That really affects my ability to care for them,” they said.

Loss of employment in the pandemic or fear of job loss and subsequent changing of insurance has complicated primary care in terms of treatment and administrative tasks, according to Dr. Loeb.

To help treat patients with acute mental health issues and manage other patients, Dr. Loeb’s practice has brought in a social worker and a therapist.

Team-based care is key in the survival of primary care practices, though providing that is difficult in the smaller clinics because of the critical mass of patients needed to make it viable, they said.

“It’s the only answer. It’s the only way you don’t drown,” Dr. Loeb added. “I’m not drowning, and I credit that to my clinic having the help to support the mental health piece of things.”
 

Rethinking workflow

Tricia McGinnis, MPP, MPH, executive vice president of the nonprofit Center for Health Care Strategies (CHCS) says complexity has forced rethinking workflow.

“A lot of the trends we’re seeing in primary care were there pre-COVID, but COVID has exacerbated those trends,” she said in an interview.

“The good news ... is that it was already becoming clear that primary care needed to provide basic mental health services and integrate with behavioral health. It had also become clear that effective primary care needed to address social issues that keep patients from accessing health care,” she said.

Expanding care teams, as Dr. Loeb mentioned, is a key strategy, according to Ms. McGinnis. Potential teams would include the clinical staff, but also social workers and community health workers – people who come from the community primary care is serving who can help build trust with patients and connect the patient to the primary care team.

“There’s a lot that needs to happen that the clinician doesn’t need to do,” she said.

Telehealth can be a big factor in coordinating the team, Ms. McGinnis added.

“It’s thinking less about who’s doing the work, but more about the work that needs to be done to keep people healthy. Then let’s think about the type of workers best suited to perform those tasks,” she said.

As for reimbursing more complex care, population-based, up-front capitated payments linked to high-quality care and better outcomes will need to replace fee-for-service models, according to Ms. McGinnis.

That will provide reliable incomes for primary care offices, but also flexibility in how each patient with different levels of complexity is managed, she said.

Ms. Greiner, Dr. Fincher, Dr. Loeb, and Ms. McGinnis have no relevant financial relationships.

Taking high-doses of marine omega-3 fatty acids, more than 1 gram daily, may raise the risk for atrial fibrillation (AFib), according to a meta-analysis of relevant research. 

However, the risk of developing AFib appears to be “relatively small” for those taking 1 gram or less of fish oil per day, Christine M. Albert, MD, chair of the department of cardiology at the Smidt Heart Institute at Cedars-Sinai, Los Angeles, told this news organization.

The study was published online Oct. 6 in the journal Circulation.

It’s estimated that 7.8% of U.S. adults – almost 19 million in all – take fish oil supplements, often unbeknownst to their health care providers, the researchers noted. Yet, the literature on the effects of omega-3 fatty acid supplementation on cardiovascular outcomes are mixed.

“Some, but not all” large-scale randomized controlled trials investigating the effects of marine omega-3 fatty acid supplements on cardiovascular outcomes have reported increased risks for AFib. The potential reasons for differing findings may be dose related, the authors note in their paper.

The goal of this meta-analysis was to “bring clarity, answers, and actionable information” to doctors and patients, said Dr. Albert. The results suggest, however, that there may not be a “straightforward answer” to whether fish oil is good or bad for AFib. Instead, the answer may depend on the dose, she added.
 

Pooled data

After screening 4,049 articles and abstracts, the researchers included in their analysis seven large-scale randomized controlled trials reporting cardiovascular outcomes of marine omega-3 fatty acids.

The trials reported results for AFib, either as prespecified outcome, adverse event, or a reason for hospitalization. Each had a minimum of 500 patients and a median follow-up of at least 1 year. 

Trials examining the effects of omega-3 fatty acids on recurrent AFib in patients with established AFib or postoperative AFib were excluded.

The seven trials enrolled a total of 81,210 patients (mean age, 65 years; 39% women); 72.6% of participants were enrolled in clinical trials testing ≤1 gram of marine omega-3 fatty acids per day and 27.4% were enrolled in clinical trials testing >1 gram of the supplement per day. The weighted average follow-up was 4.9 years.

Overall, use of omega-3 fatty acids was associated with a 25% increased risk for AFib (hazard ratio, 1.25; 95% confidence interval, 1.07-1.46; P = .013).

In analyses stratified by dose, the risk for AFib was “significantly more pronounced” in trials testing high doses of marine omega-3 fatty acid supplements (>1 gram per day: HR, 1.49; 95% CI, 1.04-2.15; P = .042) compared with those testing lower doses (≤1 gram per day: HR, 1.12; 95% CI, 1.03-1.22; P = .024; P for interaction < .001).

In meta-regression, the HR for AFib increased per 1 gram increase in daily omega-3 fatty acid dose (HR. 1.11; 95% CI, 1.06-1.15; P = .001).
 

Risk-benefit balance

“This meta-analysis adds new evidence regarding the risk of AFib in patients taking marine omega-3 fatty acid supplements,” wrote Dr. Albert and colleagues.

“Since the benefit of omega-3 fatty acids also appears to be dose dependent, the associated risk of AFib should be balanced against the benefit on atherosclerotic cardiovascular outcomes,” they suggested.

They cautioned that the meta-analysis pooled aggregate-level trial data, not individual patient data. Therefore, subgroup analyses by age or other patient level characteristics were not possible.

The risk of developing AFib increases with advancing age and is more common in men than in women. Additional risk factors include elevated blood pressure, coronary artery disease, heart failure, heart valve defects, obesity, and diabetes.

The authors said the potential risk of developing AFib with high doses of omega-3 fatty acid supplements should be discussed with patients and they should know the signs and symptoms of the condition.

The study had no specific funding. Dr. Albert has received grants from St. Jude Medical, Abbott, and Roche Diagnostics.

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

Taking high-doses of marine omega-3 fatty acids, more than 1 gram daily, may raise the risk for atrial fibrillation (AFib), according to a meta-analysis of relevant research. 

However, the risk of developing AFib appears to be “relatively small” for those taking 1 gram or less of fish oil per day, Christine M. Albert, MD, chair of the department of cardiology at the Smidt Heart Institute at Cedars-Sinai, Los Angeles, told this news organization.

The study was published online Oct. 6 in the journal Circulation.

It’s estimated that 7.8% of U.S. adults – almost 19 million in all – take fish oil supplements, often unbeknownst to their health care providers, the researchers noted. Yet, the literature on the effects of omega-3 fatty acid supplementation on cardiovascular outcomes are mixed.

“Some, but not all” large-scale randomized controlled trials investigating the effects of marine omega-3 fatty acid supplements on cardiovascular outcomes have reported increased risks for AFib. The potential reasons for differing findings may be dose related, the authors note in their paper.

The goal of this meta-analysis was to “bring clarity, answers, and actionable information” to doctors and patients, said Dr. Albert. The results suggest, however, that there may not be a “straightforward answer” to whether fish oil is good or bad for AFib. Instead, the answer may depend on the dose, she added.
 

Pooled data

After screening 4,049 articles and abstracts, the researchers included in their analysis seven large-scale randomized controlled trials reporting cardiovascular outcomes of marine omega-3 fatty acids.

The trials reported results for AFib, either as prespecified outcome, adverse event, or a reason for hospitalization. Each had a minimum of 500 patients and a median follow-up of at least 1 year. 

Trials examining the effects of omega-3 fatty acids on recurrent AFib in patients with established AFib or postoperative AFib were excluded.

The seven trials enrolled a total of 81,210 patients (mean age, 65 years; 39% women); 72.6% of participants were enrolled in clinical trials testing ≤1 gram of marine omega-3 fatty acids per day and 27.4% were enrolled in clinical trials testing >1 gram of the supplement per day. The weighted average follow-up was 4.9 years.

Overall, use of omega-3 fatty acids was associated with a 25% increased risk for AFib (hazard ratio, 1.25; 95% confidence interval, 1.07-1.46; P = .013).

In analyses stratified by dose, the risk for AFib was “significantly more pronounced” in trials testing high doses of marine omega-3 fatty acid supplements (>1 gram per day: HR, 1.49; 95% CI, 1.04-2.15; P = .042) compared with those testing lower doses (≤1 gram per day: HR, 1.12; 95% CI, 1.03-1.22; P = .024; P for interaction < .001).

In meta-regression, the HR for AFib increased per 1 gram increase in daily omega-3 fatty acid dose (HR. 1.11; 95% CI, 1.06-1.15; P = .001).
 

Risk-benefit balance

“This meta-analysis adds new evidence regarding the risk of AFib in patients taking marine omega-3 fatty acid supplements,” wrote Dr. Albert and colleagues.

“Since the benefit of omega-3 fatty acids also appears to be dose dependent, the associated risk of AFib should be balanced against the benefit on atherosclerotic cardiovascular outcomes,” they suggested.

They cautioned that the meta-analysis pooled aggregate-level trial data, not individual patient data. Therefore, subgroup analyses by age or other patient level characteristics were not possible.

The risk of developing AFib increases with advancing age and is more common in men than in women. Additional risk factors include elevated blood pressure, coronary artery disease, heart failure, heart valve defects, obesity, and diabetes.

The authors said the potential risk of developing AFib with high doses of omega-3 fatty acid supplements should be discussed with patients and they should know the signs and symptoms of the condition.

The study had no specific funding. Dr. Albert has received grants from St. Jude Medical, Abbott, and Roche Diagnostics.

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

Taking high-doses of marine omega-3 fatty acids, more than 1 gram daily, may raise the risk for atrial fibrillation (AFib), according to a meta-analysis of relevant research. 

However, the risk of developing AFib appears to be “relatively small” for those taking 1 gram or less of fish oil per day, Christine M. Albert, MD, chair of the department of cardiology at the Smidt Heart Institute at Cedars-Sinai, Los Angeles, told this news organization.

The study was published online Oct. 6 in the journal Circulation.

It’s estimated that 7.8% of U.S. adults – almost 19 million in all – take fish oil supplements, often unbeknownst to their health care providers, the researchers noted. Yet, the literature on the effects of omega-3 fatty acid supplementation on cardiovascular outcomes are mixed.

“Some, but not all” large-scale randomized controlled trials investigating the effects of marine omega-3 fatty acid supplements on cardiovascular outcomes have reported increased risks for AFib. The potential reasons for differing findings may be dose related, the authors note in their paper.

The goal of this meta-analysis was to “bring clarity, answers, and actionable information” to doctors and patients, said Dr. Albert. The results suggest, however, that there may not be a “straightforward answer” to whether fish oil is good or bad for AFib. Instead, the answer may depend on the dose, she added.
 

Pooled data

After screening 4,049 articles and abstracts, the researchers included in their analysis seven large-scale randomized controlled trials reporting cardiovascular outcomes of marine omega-3 fatty acids.

The trials reported results for AFib, either as prespecified outcome, adverse event, or a reason for hospitalization. Each had a minimum of 500 patients and a median follow-up of at least 1 year. 

Trials examining the effects of omega-3 fatty acids on recurrent AFib in patients with established AFib or postoperative AFib were excluded.

The seven trials enrolled a total of 81,210 patients (mean age, 65 years; 39% women); 72.6% of participants were enrolled in clinical trials testing ≤1 gram of marine omega-3 fatty acids per day and 27.4% were enrolled in clinical trials testing >1 gram of the supplement per day. The weighted average follow-up was 4.9 years.

Overall, use of omega-3 fatty acids was associated with a 25% increased risk for AFib (hazard ratio, 1.25; 95% confidence interval, 1.07-1.46; P = .013).

In analyses stratified by dose, the risk for AFib was “significantly more pronounced” in trials testing high doses of marine omega-3 fatty acid supplements (>1 gram per day: HR, 1.49; 95% CI, 1.04-2.15; P = .042) compared with those testing lower doses (≤1 gram per day: HR, 1.12; 95% CI, 1.03-1.22; P = .024; P for interaction < .001).

In meta-regression, the HR for AFib increased per 1 gram increase in daily omega-3 fatty acid dose (HR. 1.11; 95% CI, 1.06-1.15; P = .001).
 

Risk-benefit balance

“This meta-analysis adds new evidence regarding the risk of AFib in patients taking marine omega-3 fatty acid supplements,” wrote Dr. Albert and colleagues.

“Since the benefit of omega-3 fatty acids also appears to be dose dependent, the associated risk of AFib should be balanced against the benefit on atherosclerotic cardiovascular outcomes,” they suggested.

They cautioned that the meta-analysis pooled aggregate-level trial data, not individual patient data. Therefore, subgroup analyses by age or other patient level characteristics were not possible.

The risk of developing AFib increases with advancing age and is more common in men than in women. Additional risk factors include elevated blood pressure, coronary artery disease, heart failure, heart valve defects, obesity, and diabetes.

The authors said the potential risk of developing AFib with high doses of omega-3 fatty acid supplements should be discussed with patients and they should know the signs and symptoms of the condition.

The study had no specific funding. Dr. Albert has received grants from St. Jude Medical, Abbott, and Roche Diagnostics.

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

A comparison of long-term survival between patients who either did or did not undergo permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) revealed no differences, according to results of the SWEDEHEART observational study.

The nationwide population-based cohort study included all patients who underwent transfemoral TAVR in Sweden from 2008 to 2018.
 

Most frequent complications

While newer-generation aortic valve prostheses are less likely to necessitate PPI, the need for PPI is higher after TAVR than after surgical aortic valve replacement (SAVR), and the need for PPI remains the most frequent complication after TAVR, the study authors noted. Use of self-expandable valves, deep prosthetic valve implantation, preprocedural conduction disturbances, older age, and a high number of comorbidities are among the risk factors for PPI following TAVR.

With prior studies producing conflicting results, the authors stated, the impact of PPI after TAVR remains unknown. Expanding use of TAVR to include younger and low-risk patients with a long life expectancy underscores the importance of gaining greater understand of the impact of PPI after TAVR. Accordingly, the study was conducted to investigate long-term, clinically important outcomes in this post-TAVR population.

Out of 4,750 patients who underwent TAVR in the study period, 3,420 patients in SWEDEHEART met study criteria, with 481 (14.1%) undergoing PPI within 30 days after TAVR, and 2,939 not receiving a pacemaker. PPI exposure was defined as implantation of a permanent pacemaker or implantable cardioverter-defibrillator. The study primary outcome was all-cause mortality, with cardiovascular death, heart failure, and endocarditis as secondary outcomes. It was reported in JACC: Cardiovascular Interventions.
 

Similar survival

Mean patient age was 81.3 years (50.4% female). The rate for all-cause mortality in those with no pacemaker was 11.4 per 100 patient years and 13.1 for those with a pacemaker (hazard ratio, 1.04; 95% confidence interval, 0.89-1.23). The cardiovascular death rate in the no-pacemaker group was 6.0 per 100 patient years and 7.1 per 100 patient years in the pacemaker group (HR, 0.96; 95% CI, 0.75-1.23). For heart failure the rates were 4.5 per 100 patient years in the no pacemaker group and 6.3 in the pacemaker group (HR, 1.22; 95% CI, 0.93-1.672). Endocarditis rates were 1.2 and 1.1 per 100 patient years in the no pacemaker and pacemaker groups, respectively (HR, 0.93; 95% CI, 0.51-1.71).

The authors pointed out that their prior study had found PPI after SAVR in almost 25,000 patients to be associated with increased all-cause mortality and heart failure rates. Patients who undergo TAVR, however, are older and have more comorbidities than patients who undergo SAVR.

It is thus likely that patients who undergo TAVR die of other causes before the negative effects of their pacemaker become clinically evident.

Also, the incidence of conduction abnormalities increases with age, making it more likely that beneficial effects of pacemakers occur in older patients rather than younger ones, counterbalancing the detrimental effects to a larger extent.
 

Reduce PPI rates after TAVR

The study authors also observed that, although they did not find increased mortality or heart failure in patients who underwent PPI, PPI is associated with risks, including lead- and pocket-related complications, other traumatic complications, longer hospital stays and higher societal costs. These factors justify the search for strategies to reduce PPI rates after TAVR.

“Our study adds important information about the prognosis in patients who received a permanent pacemaker implantation following TAVR,” study author Natalie Glaser, MD, PhD, said in an interview. “Increased knowledge about prognosis after TAVR in different patient populations has important implications for preoperative risk stratification and can help to optimize postoperative follow-up and treatment for these patients.” Future studies, Dr. Glaser added, should include younger and low-risk patients with longer follow-up to confirm the present findings. 
 

Balancing factors

In an accompanying editorial, Antonio J. Muñoz-García, MD, PhD, and Erika Muñoz-García, MD also noted factors potentially counterbalancing and masking adverse effects of PPI, echoing some mentioned by the study authors. Among those without PPI, 10%-50% develop new-onset left bundle branch block (LBBB) after TAVR. LBBB is a known marker of low long-term survival in TAVR populations, producing intraventricular dyssynchrony leading potentially to left ventricular dysfunction or development of complete atrioventricular block with higher mortality risk in those without pacemakers. PPI, as well, can be protective against unexpected death in those with advanced conduction disorders. Still, they point out, PPI can entail lead dysfunction, need for generator replacement, infection, and tricuspid valve regurgitation.

Commenting in an interview that an observed trend of a greater increase in events in the group of patients with pacemakers for the first 4 years is consistent with prior studies, Dr. Antonio Muñoz-García said: “This can be explained because long-term survival in the TAVI population is conditioned by comorbidities. It is true that the presence of a pacemaker can cause left ventricular ejection fraction to deteriorate and therefore condition heart failure and increased mortality. But the involvement of the pacemaker in left ventricular function in patients with TAVI is multifactorial and depends on the indication of the pacemaker, whether prophylactic or absolute, on the time-dependent pacing, whether or not the patients prior to TAVI present with alterations in atrioventricular conduction [and therefore could benefit from the implantation of pacemakers], as well as the forms of pacing optimization [resynchronization, hisian pacing, etc]. All of these are issues to be considered in clinical practice.”

The editorialists concluded: “To date, the impact of PPI on late clinical outcomes after TAVR remains controversial; however, this study to some extent helps clarify this controversy.” In accord with the study authors, they called for reductions in PPI rates and long-term clinical follow-up.

The study was funded by several Swedish research organizations. The study investigators and editorial authors declared having no disclosures.

A comparison of long-term survival between patients who either did or did not undergo permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) revealed no differences, according to results of the SWEDEHEART observational study.

The nationwide population-based cohort study included all patients who underwent transfemoral TAVR in Sweden from 2008 to 2018.
 

Most frequent complications

While newer-generation aortic valve prostheses are less likely to necessitate PPI, the need for PPI is higher after TAVR than after surgical aortic valve replacement (SAVR), and the need for PPI remains the most frequent complication after TAVR, the study authors noted. Use of self-expandable valves, deep prosthetic valve implantation, preprocedural conduction disturbances, older age, and a high number of comorbidities are among the risk factors for PPI following TAVR.

With prior studies producing conflicting results, the authors stated, the impact of PPI after TAVR remains unknown. Expanding use of TAVR to include younger and low-risk patients with a long life expectancy underscores the importance of gaining greater understand of the impact of PPI after TAVR. Accordingly, the study was conducted to investigate long-term, clinically important outcomes in this post-TAVR population.

Out of 4,750 patients who underwent TAVR in the study period, 3,420 patients in SWEDEHEART met study criteria, with 481 (14.1%) undergoing PPI within 30 days after TAVR, and 2,939 not receiving a pacemaker. PPI exposure was defined as implantation of a permanent pacemaker or implantable cardioverter-defibrillator. The study primary outcome was all-cause mortality, with cardiovascular death, heart failure, and endocarditis as secondary outcomes. It was reported in JACC: Cardiovascular Interventions.
 

Similar survival

Mean patient age was 81.3 years (50.4% female). The rate for all-cause mortality in those with no pacemaker was 11.4 per 100 patient years and 13.1 for those with a pacemaker (hazard ratio, 1.04; 95% confidence interval, 0.89-1.23). The cardiovascular death rate in the no-pacemaker group was 6.0 per 100 patient years and 7.1 per 100 patient years in the pacemaker group (HR, 0.96; 95% CI, 0.75-1.23). For heart failure the rates were 4.5 per 100 patient years in the no pacemaker group and 6.3 in the pacemaker group (HR, 1.22; 95% CI, 0.93-1.672). Endocarditis rates were 1.2 and 1.1 per 100 patient years in the no pacemaker and pacemaker groups, respectively (HR, 0.93; 95% CI, 0.51-1.71).

The authors pointed out that their prior study had found PPI after SAVR in almost 25,000 patients to be associated with increased all-cause mortality and heart failure rates. Patients who undergo TAVR, however, are older and have more comorbidities than patients who undergo SAVR.

It is thus likely that patients who undergo TAVR die of other causes before the negative effects of their pacemaker become clinically evident.

Also, the incidence of conduction abnormalities increases with age, making it more likely that beneficial effects of pacemakers occur in older patients rather than younger ones, counterbalancing the detrimental effects to a larger extent.
 

Reduce PPI rates after TAVR

The study authors also observed that, although they did not find increased mortality or heart failure in patients who underwent PPI, PPI is associated with risks, including lead- and pocket-related complications, other traumatic complications, longer hospital stays and higher societal costs. These factors justify the search for strategies to reduce PPI rates after TAVR.

“Our study adds important information about the prognosis in patients who received a permanent pacemaker implantation following TAVR,” study author Natalie Glaser, MD, PhD, said in an interview. “Increased knowledge about prognosis after TAVR in different patient populations has important implications for preoperative risk stratification and can help to optimize postoperative follow-up and treatment for these patients.” Future studies, Dr. Glaser added, should include younger and low-risk patients with longer follow-up to confirm the present findings. 
 

Balancing factors

In an accompanying editorial, Antonio J. Muñoz-García, MD, PhD, and Erika Muñoz-García, MD also noted factors potentially counterbalancing and masking adverse effects of PPI, echoing some mentioned by the study authors. Among those without PPI, 10%-50% develop new-onset left bundle branch block (LBBB) after TAVR. LBBB is a known marker of low long-term survival in TAVR populations, producing intraventricular dyssynchrony leading potentially to left ventricular dysfunction or development of complete atrioventricular block with higher mortality risk in those without pacemakers. PPI, as well, can be protective against unexpected death in those with advanced conduction disorders. Still, they point out, PPI can entail lead dysfunction, need for generator replacement, infection, and tricuspid valve regurgitation.

Commenting in an interview that an observed trend of a greater increase in events in the group of patients with pacemakers for the first 4 years is consistent with prior studies, Dr. Antonio Muñoz-García said: “This can be explained because long-term survival in the TAVI population is conditioned by comorbidities. It is true that the presence of a pacemaker can cause left ventricular ejection fraction to deteriorate and therefore condition heart failure and increased mortality. But the involvement of the pacemaker in left ventricular function in patients with TAVI is multifactorial and depends on the indication of the pacemaker, whether prophylactic or absolute, on the time-dependent pacing, whether or not the patients prior to TAVI present with alterations in atrioventricular conduction [and therefore could benefit from the implantation of pacemakers], as well as the forms of pacing optimization [resynchronization, hisian pacing, etc]. All of these are issues to be considered in clinical practice.”

The editorialists concluded: “To date, the impact of PPI on late clinical outcomes after TAVR remains controversial; however, this study to some extent helps clarify this controversy.” In accord with the study authors, they called for reductions in PPI rates and long-term clinical follow-up.

The study was funded by several Swedish research organizations. The study investigators and editorial authors declared having no disclosures.

A comparison of long-term survival between patients who either did or did not undergo permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) revealed no differences, according to results of the SWEDEHEART observational study.

The nationwide population-based cohort study included all patients who underwent transfemoral TAVR in Sweden from 2008 to 2018.
 

Most frequent complications

While newer-generation aortic valve prostheses are less likely to necessitate PPI, the need for PPI is higher after TAVR than after surgical aortic valve replacement (SAVR), and the need for PPI remains the most frequent complication after TAVR, the study authors noted. Use of self-expandable valves, deep prosthetic valve implantation, preprocedural conduction disturbances, older age, and a high number of comorbidities are among the risk factors for PPI following TAVR.

With prior studies producing conflicting results, the authors stated, the impact of PPI after TAVR remains unknown. Expanding use of TAVR to include younger and low-risk patients with a long life expectancy underscores the importance of gaining greater understand of the impact of PPI after TAVR. Accordingly, the study was conducted to investigate long-term, clinically important outcomes in this post-TAVR population.

Out of 4,750 patients who underwent TAVR in the study period, 3,420 patients in SWEDEHEART met study criteria, with 481 (14.1%) undergoing PPI within 30 days after TAVR, and 2,939 not receiving a pacemaker. PPI exposure was defined as implantation of a permanent pacemaker or implantable cardioverter-defibrillator. The study primary outcome was all-cause mortality, with cardiovascular death, heart failure, and endocarditis as secondary outcomes. It was reported in JACC: Cardiovascular Interventions.
 

Similar survival

Mean patient age was 81.3 years (50.4% female). The rate for all-cause mortality in those with no pacemaker was 11.4 per 100 patient years and 13.1 for those with a pacemaker (hazard ratio, 1.04; 95% confidence interval, 0.89-1.23). The cardiovascular death rate in the no-pacemaker group was 6.0 per 100 patient years and 7.1 per 100 patient years in the pacemaker group (HR, 0.96; 95% CI, 0.75-1.23). For heart failure the rates were 4.5 per 100 patient years in the no pacemaker group and 6.3 in the pacemaker group (HR, 1.22; 95% CI, 0.93-1.672). Endocarditis rates were 1.2 and 1.1 per 100 patient years in the no pacemaker and pacemaker groups, respectively (HR, 0.93; 95% CI, 0.51-1.71).

The authors pointed out that their prior study had found PPI after SAVR in almost 25,000 patients to be associated with increased all-cause mortality and heart failure rates. Patients who undergo TAVR, however, are older and have more comorbidities than patients who undergo SAVR.

It is thus likely that patients who undergo TAVR die of other causes before the negative effects of their pacemaker become clinically evident.

Also, the incidence of conduction abnormalities increases with age, making it more likely that beneficial effects of pacemakers occur in older patients rather than younger ones, counterbalancing the detrimental effects to a larger extent.
 

Reduce PPI rates after TAVR

The study authors also observed that, although they did not find increased mortality or heart failure in patients who underwent PPI, PPI is associated with risks, including lead- and pocket-related complications, other traumatic complications, longer hospital stays and higher societal costs. These factors justify the search for strategies to reduce PPI rates after TAVR.

“Our study adds important information about the prognosis in patients who received a permanent pacemaker implantation following TAVR,” study author Natalie Glaser, MD, PhD, said in an interview. “Increased knowledge about prognosis after TAVR in different patient populations has important implications for preoperative risk stratification and can help to optimize postoperative follow-up and treatment for these patients.” Future studies, Dr. Glaser added, should include younger and low-risk patients with longer follow-up to confirm the present findings. 
 

Balancing factors

In an accompanying editorial, Antonio J. Muñoz-García, MD, PhD, and Erika Muñoz-García, MD also noted factors potentially counterbalancing and masking adverse effects of PPI, echoing some mentioned by the study authors. Among those without PPI, 10%-50% develop new-onset left bundle branch block (LBBB) after TAVR. LBBB is a known marker of low long-term survival in TAVR populations, producing intraventricular dyssynchrony leading potentially to left ventricular dysfunction or development of complete atrioventricular block with higher mortality risk in those without pacemakers. PPI, as well, can be protective against unexpected death in those with advanced conduction disorders. Still, they point out, PPI can entail lead dysfunction, need for generator replacement, infection, and tricuspid valve regurgitation.

Commenting in an interview that an observed trend of a greater increase in events in the group of patients with pacemakers for the first 4 years is consistent with prior studies, Dr. Antonio Muñoz-García said: “This can be explained because long-term survival in the TAVI population is conditioned by comorbidities. It is true that the presence of a pacemaker can cause left ventricular ejection fraction to deteriorate and therefore condition heart failure and increased mortality. But the involvement of the pacemaker in left ventricular function in patients with TAVI is multifactorial and depends on the indication of the pacemaker, whether prophylactic or absolute, on the time-dependent pacing, whether or not the patients prior to TAVI present with alterations in atrioventricular conduction [and therefore could benefit from the implantation of pacemakers], as well as the forms of pacing optimization [resynchronization, hisian pacing, etc]. All of these are issues to be considered in clinical practice.”

The editorialists concluded: “To date, the impact of PPI on late clinical outcomes after TAVR remains controversial; however, this study to some extent helps clarify this controversy.” In accord with the study authors, they called for reductions in PPI rates and long-term clinical follow-up.

The study was funded by several Swedish research organizations. The study investigators and editorial authors declared having no disclosures.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.