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BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
EXPERT ANALYSIS FROM HEART RHYTHM 2018