Catheter Ablation Improves, May Reverse HFpEF Symptoms in Patients With AF

Catheter ablation in patients with concomitant atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) improves symptoms and functional status and may reverse myocardial fibrosis and reduce HF progression.1

In a presentation at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, Jonathan Piccini, MD, director of cardiac electrophysiology at Duke University Health System, discussed the potential for catheter ablation in this patient population by citing the effects of the process on symptoms of HFpEF in prior research and ongoing trials.1

“Regardless of which condition is driving which, when they are together, the outcomes are worse, and the symptoms are worse,” Piccini told HCPLive in an exclusive interview. “Reducing or minimizing the amount of AF that a patient with HFpEF has is important, independent of the subtype of HFpEF that they have.”

The presentation contributes to an ongoing debate regarding the effectiveness of the procedure in reducing or reversing HFpEF – in particular, an analysis published in 2024 showed no notable association between catheter ablation and HFpEF events. The investigators in this study collected 12 randomized controlled trials with a total of 2465 participants, of whom 1552 had HF with reduced ejection fraction (HFrEF) and 913 with HFpEF.2

Based on this analysis, catheter ablation was associated with a reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72) – however, there was no documented benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32). The procedure also reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.7), but a differential association was not found in HFpEF (RR, 0.91; 95% CI, 0.46-1.79).2

In this presentation, however, Piccini cites a 2023 study published in JACC, which indicated that AF ablation successfully improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with AF and HFpEF. Of the 31 included patients, 16 were randomly assigned to receive AF ablation, while 15 were assigned to medical therapy. After 6 months of treatment, ablation reduced the primary outcome of peak pulmonary capillary wedge pressure from baseline (30.4 +/- 4.2 to 25.4 +/- 4.5 mmHg; P <.01). Improvements were also noted in peak relative VO2 and NT-proBNP.3

The 2021 CABANA-HF trial, also cited in the presentation, displayed substantial improvements in survival, freedom from AF recurrence, and quality of life following ablation compared to standard drug therapy. Of the 778 patients enrolled, 378 received ablation and 400 received medical treatment. The ablation arm ultimately exhibited a 36% relative reduction in the primary composite endpoint of death, disabling stroke, serious bleeding, or cardiac arrest, and a 43% relative reduction in all-cause mortality compared with drug therapy.4

Piccini goes on to highlight ongoing trials investigating the potential connection between HFpEF with AF and atrial fibrillation, including CABA-HFpEF, STABLE-SR IV, and CASTLE HFpEF, all of which are actively recruiting. CABA-HFpEF is comparing catheter ablation with usual care, while STABLE-SR IV examines the procedure versus AAD, and CASTLE HFpEF compares it to guideline-directed medical therapy.1

Ultimately, however, Piccini shares his belief that AF may be placed unduly on a pedestal as a treatment target for HFpEF. He acknowledges other variants of the condition, as well as patients with different forms of HF, are equally prevalent.1

“I think AF burden sometimes gets overemphasized,” Piccini said. “It’s odd for me to say that, because I think it’s incredibly important. The way I choose to think about it is that it’s more about how much AF someone is exposed to, and the lower we can get that, the better off they will be.”

Editors’ Note: Piccini reports disclosures with Abbott, Amgen, Bayer, Medtronic, Lilly, Milestone Pharmaceuticals, and others.

References

1. Piccini J. Can catheter ablation of atrial fibrillation reverse HFpEF? Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

2. Oraii A, McIntyre WF, Parkash R, et al. Atrial fibrillation ablation in heart failure with reduced vs preserved ejection fraction. JAMA Cardiol. 2024;9(6):545. doi:10.1001/jamacardio.2024.0675

3. Chieng, D, Sugumar, H, Segan, L. et al. Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial. J Am Coll Cardiol HF. 2023 Jun, 11 (6) 646–658. https://doi.org/10.1016/j.jchf.2023.01.008

4. Packer DL, Piccini JP, Monahan KH, et al. Ablation versus drug therapy for atrial fibrillation in heart failure. Circulation. 2021;143(14):1377-1390. doi:10.1161/circulationaha.120.050991