SAN FRANCISCO – Catheter ablation of atrial fibrillation (AFib) in the roughly one-third of patients with heart failure enrolled in the CABANA multicenter, randomized trial produced striking, statistically significant improvements both in the study’s primary, combined endpoint and in all-cause mortality in intention-to-treat analyses.
These findings, from prespecified secondary analyses, contrasted with the study’s overall result, which showed no benefit in the primary endpoint analysis in the total study population of 2,204 patients with AFib (JAMA. 2019 Apr 2;321:1261-74). They are also at odds with the primary endpoint result in the two-thirds of enrolled patients without heart failure, which showed no significant between-group differences in these two outcome measures among the patients assigned to the catheter ablation arm and the study’s control, which was medical management arm.
Among the 778 AFib patients enrolled in CABANA with any form of heart failure (35% of the total study enrollment), the incidence of the study’s primary endpoint – the combined rate of death, disabling stroke, serious bleeding, or cardiac arrest during a median follow-up of slightly more than 4 years – was 36% lower among the catheter-ablated heart failure patients than in the heart failure patients assigned to medical treatment, according to an intention-to-treat analysis, which was a statistically significant difference. The incidence of all-cause mortality during follow-up was 43% lower in the ablated heart failure patients, compared with the controls, Douglas L. Packer, MD, said at the annual scientific sessions of the Heart Rhythm Society.
In contrast, among enrolled patients without heart failure, the intention-to-treat primary endpoint was 6% higher in the ablated patients, and all-cause mortality was a relative 27% higher, although neither difference was statistically significant.
It’s a “little surprising” that the results showed this much benefit in the patients with heart failure, said Dr. Packer, professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of the CABANA (Catheter Ablation vs Anti-Arrhythmic Drug Therapy for Atrial Fibrillation) trial. “I think these data confirm the results of the CASTLE-AF trial, but without some of the glitches some people have cited” about that study, such as concerns about a high level of patient selection in CASTLE-AF and its relatively modest number of enrolled patients, he said in an interview.
The CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) study, run entirely in patients with heart failure with reduced ejection fraction and AFib, showed a statistically significant improvement in patient survival and heart failure hospitalization after catheter ablation compared with medical management (N Engl J Med. 2018 Feb 1;378:417-27). Prior to the CASTLE-AF report, results from several other small studies (J Interv Card Electrophysiol. 2018 Oct;53:19-29), as well as those from the AATAC trial (Circulation. 2016 Apr 26;133:1637-44), also showed consistent evidence for benefit from catheter ablation in patients with heart failure and AFib, noted CABANA coinvestigator Jonathan P. Piccini, MD, during a separate talk at the meeting.
“The improvement of cardiovascular outcomes with ablation in patients with heart failure and AFib is consistent across multiple trials, at least with respect to heart failure with reduced ejection fraction” concluded Dr. Piccini, a cardiac electrophysiologist at Duke University in Durham, N.C.
As a result of the new heart failure analysis, “I think the guidelines will change,” predicted Dr. Packer, with catheter ablation receiving a firmer endorsement for patients with heart failure the next time U.S. guidelines for heart failure and AFib management are updated. The findings say “there is substantial benefit of catheter ablation in heart failure patients, but I don’t think our findings lessen the utility of ablation in patients without heart failure,” he stressed. Even patients without heart failure showed reduction in AFib burden and improvement in quality of life that were similar to what was seen in the heart failure patients.
The new report from CABANA of benefit from AFib catheter ablation in patients with heart failure “absolutely advances the evidence,” commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern University in Chicago. “A number of us were quite circumspect about this based on the CASTLE-AF data, but the new CABANA analyses have addressed our anxiety that the CASTLE-AF results were just by chance.” The new CABANA analyses “may not confirm CASTLE-AF, but it enriches the conversation and makes it possible that we are seeing benefit in some patients with heart failure who get ablated.”
Dr. Yancy, who chaired the most recent update to the U.S. heart failure management guideline (J Am Coll Cardiol. 2017 Aug 8;70:776-803) stopped short of saying that the cumulative evidence now supports a guideline change, but he acknowledged in an interview that the evidence could legitimately influence practice. Catheter ablation should now be “strongly considered” in patients with heart failure and AFib, he said, although he also had three qualifications for opting for this approach: Patients must already be on guideline-directed medical therapy for their heart failure, the catheter ablation needs to be performed by an experienced and skilled operator, and follow-up surveillance must focus on both the patient’s AFib and heart failure. “It’s absolutely appropriate to consider catheter ablation” for heart failure patients, but the evidence is not yet there for guideline change, Dr. Yancy concluded.
It remains uncertain why catheter ablation of AFib should be more effective in patients with heart failure than in those without. Dr. Packer speculated that one reason may be the heart rate reduction that AFib ablation produces may especially benefit heart failure patients. An additional helpful effect of ablation in heart failure patients may be reducing heart rate variability. Another notable finding of the new analysis was that 79% of patients with heart failure in CABANA had heart failure with preserved ejection fraction, with a left ventricular ejection fraction of at least 50%. “Getting rid of AFib in patients with heart failure with preserved ejection fraction will be more important than we have thought,” Dr. Packer said.
Other new CABANA analyses presented for the first time in separate talks at the meeting also showed that, while catheter ablation had no meaningful difference in effect on outcomes based on the sex of patients, both age and minority ethnic and racial status appeared to make a substantial difference. For CABANA’s primary endpoint, catheter ablation was especially effective for improving outcomes in patients 64 years old or younger, and the analysis showed a signal of possibly worse outcomes in patients who were at least 75 years old. The “substantially” better outcomes in minority-group patients represented the largest between-group difference among subgroups seen in CABANA and is a “big deal,” said Dr. Packer, who predicted that future catheter ablation use will likely rise in patients with heart failure, in younger patients, and in minority patients.
Dr. Piccini noted that, “it’s possible that CABANA identified some patient subgroups that do really well after ablation, but the problem is that, in the United States, we now often don’t treat” minority patients or those with reduced left ventricular ejection fractions with ablation, according to recent registry findings.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and/or received research funding from these four companies, as well as numerous drug and device companies, and has a financial interest in a licensed AFib mapping technology. Dr. Piccini has ties Boston Scientific, Medtronic, and numerous other drug and device companies, and disclosed an unspecified relationship with GlaxoSmithKline. Dr. Yancy disclosed an unspecified relationship with Abbott Laboratories.
SOURCE: Packer DL. Heart Rhythm 2019, Abstract S-AB14-06.