Roughly a third of patients with heart failure also have atrial fibrillation, a comorbid combination notorious for working synergistically to worsen a patient’s quality of life and life expectancy.
During the past year, radiofrequency catheter ablation of atrial fibrillation in patients with both conditions has gathered steam as a way to intervene in at least selected patients, driven by study results that featured attention-grabbing reductions in death and cardiovascular hospitalizations.
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Dr. Stavros Stavrakis
The evidence favoring catheter ablation of atrial fibrillation (AFib) in patients with heart failure, particularly patients with heart failure with reduced ejection fraction (HFrEF), ramped up in 2019, spurred largely by a subgroup analysis from the CABANA trial, the largest randomized comparison by far of AFib ablation with antiarrhythmic drug treatment with 2,204 patients.
The past few months also featured release of two meta-analyses that took the CABANA results into account plus findings from about a dozen earlier randomized studies. Both meta-analyses, as well as the heart failure analysis from CABANA, all point in one direction, as stated in the conclusion of one of the meta-analyses: “In patients with AFib, catheter ablation is associated with all-cause mortality benefit, compared with medical therapy, that is driven by patients with AFib and HFrEF. Catheter ablation is safe and reduces cardiovascular hospitalizations and recurrences of atrial arrhythmias” both in patients with paroxysmal and persistent AFib,” wrote Stavros Stavrakis, MD, and his associates in their systematic review of 18 randomized, controlled trials of catheter ablation of AFib in a total of 4,464 patients with or without heart failure (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: e007414).
Despite these new data and analyses, clinicians seem to have very mixed reactions. Some call for an upgraded recommendation by professional societies that would support more aggressive use of AFib ablation in heart failure patients, and the anecdotal impressions of people who manage these patients are that ablation procedures have recently increased. But others advise caution, and note that in their opinion the efficacy data remain preliminary; the procedure has safety, logistical, and economic concerns; and questions remain about the ability of all active ablation programs to consistently deliver the results seen in published trials.
The meta-analysis led by Dr. Stavrakis showed that catheter ablation of AFib cut all-cause mortality during follow-up by a statistically significant 31%, compared with medical therapy, in all patients regardless of their heart failure status. But in patients with HFrEF, the reduction was 48%, along with a 38% cut in cardiovascular hospitalizations. In contrast, patients without heart failure who underwent AFib ablation showed no significant change in their all-cause mortality, compared with medical management of these patients.
“Based both on our meta-analysis and the CABANA data, patients with AFib most likely to benefit from ablation are patients younger than 65 and those with heart failure,” summed up Dr. Stavrakis, a cardiac electrophysiologist at the Heart Rhythm Institute of the University of Oklahoma in Oklahoma City.
The second meta-analysis, which initially appeared in July, analyzed data from 11 randomized trials of catheter ablations compared with anti-arrhythmic medical therapy for rate or rhythm control with in a total of 3,598 patients who all had heart failure, again including the patients enrolled in the CABANA study. The results showed a significant 49% relative drop in all cause mortality with ablation compared with medical treatment, and a statistically significant 56% cut in hospitalizations, as well as a significant, nearly 7% average, absolute improvement in left ventricular ejection fraction, plus benefits for preventing arrhythmia recurrence and improving quality of life (Eur Heart J. 2019 Jul 11. doi: 10.1093/eurheartj/ehz443).
“The magnitude of the effect seen in the meta-analysis, a 49% reduction in total mortality and a 56% reduction in hospitalizations, is rather staggering, and is larger than typically quoted for other medical interventions or device therapy in heart failure. The treatment effect was uniform among studies, and entirely compatible with the changes in left ventricular function, exercise capacity, and heart failure symptoms. Therefore, although more data are desirable, there are already arguably sufficient data to understand a great deal regarding the impact of a fib ablation,” commented Ross J. Hunter, MRCP, a cardiac electrophysiologist at Barts Heart Centre in London, and his associates in an editorial about this meta-analysis (Eur Heart J. 2019 Oct 22. doi: 10.1093/eurheartj/ehz704).
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Dr. Douglas L. Packer
The heart failure analysis of CABANA (Catheter Ablation vs. Anti-Arrhythmic Drug Therapy for Atrial Fibrillation Trial) itself also showed striking findings when first reported at the annual scientific sessions of the Heart Rhythm Society last May. In presentations he made at this meeting, Douglas L. Packer, MD, CABANA’s lead investigator, reported details of a prespecified subgroup analysis of the 778 patients enrolled in CABANA who had heart failure at baseline, slightly more than a third of the total study enrollment. This was more than double the number of patients identified as specifically having heart failure at entry in the initial publication of CABANA’s findings (JAMA. 2019 Mar 15;321[134]:1261-74). Comparison of the 378 patients with heart failure and randomized to undergo ablation with the 400 with heart failure randomized to medical treatment showed a 36% reduction in the study’s primary, composite endpoint relative to the control group in an intention-to-treat analysis, and a 43% relative cut in all-cause mortality during follow-up, Dr. Packer reported at the May meeting. (As of early November 2019, these results had not yet appeared in a published article.) In contrast, in the 1,422 CABANA patients randomized who did not have heart failure, ablation produced results for these endpoints that were similar to and not statistically different from the outcomes in patients treated medically, said Dr. Packer, a cardiac electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.
The CABANA results added to what had been previously reported from two other landmark studies that documented incremental efficacy of AFib ablation compared with medical treatment in patients with heart failure: The AATAC (Ablation vs Amiodarone for Treatment of AFib in Patients With Congestive HF and an Implanted Device) study, which randomized 203 patients (Circulation. 2016 Apr 26;133[17]:1637-44), and CASTLE-AF (Catheter Ablation vs. Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation) trial, which randomized 363 patients (N Engl J Med. 2018 Feb 1;378[5]:417-27). These three studies contributed the most patients and outcomes to the two recent meta-analyses.
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Dr. Jonathan P. Piccini
“The CASTLE-AF and AATAC trials both showed improved cardiovascular outcomes with ablation in patients with heart failure and AFib. The meta-analysis [by Dr. Stavrakis and his associates] and CABANA subgroup analysis further support use of catheter ablation to improve the outcomes in these patients,” noted Jonathan P. Piccini, MD, a cardiac electrophysiologist at Duke University, Durham, N.C., and a CABANA coinvestigator.
“The CABANA trial was very important because it confirmed the safety of catheter ablation, and more importantly suggested that patients with heart failure may benefit the most [from AFib ablation]. The evidence is very strong to advocate ablation as first-line therapy for selected patients with heart failure. Perhaps the optimal patients are those with [New York Heart Association] class I-III or ambulatory class IV heart failure who are on optimized, guideline-directed medical therapy. We have enough data to make this a class I recommendation. The question that remains is whether this is a cost effective strategy. Because it lowers rehospitalization and death, I suspect it is,” said Luigi Di Biase, MD, lead investigator of AATAC, and director of arrhythmia services at Montefiore Medical Center and professor of medicine at Albert Einstein College of Medicine, both in New York.