Catheter Ablation Versus Medical Therapy in Atrial Fibrillation With Heart Failure With Reduced or Mildly Reduced Ejection Fraction: A GRADE ‐Assessed Systematic Review and Meta‐Analysis

Q: What are the key findings of this study?

Catheter ablation significantly reduced all-cause mortality (RR 0.61) and cardiovascular mortality (RR 0.46) compared with medical therapy in patients with atrial fibrillation and HFrEF/HFmrEF.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Atrial fibrillation with heart failure with reduced or mildly reduced ejection fraction (n=131492). Intervention: Catheter ablation vs. Conventional medical therapy. Primary outcome: All-cause mortality (RR 0.61, 95% CI 0.51-0.71, p=<0.00001).

Q: What does this research mean for the field?

Catheter ablation significantly reduces all-cause and cardiovascular mortality and improves left ventricular ejection fraction compared with medical therapy in patients with atrial fibrillation and heart failure with reduced or mildly reduced ejection fraction. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Aleena Amir Malik; Nasir Saeed; Goodluck Oparaugo; Muhammad Waqar Shahid; Waqas Kareem; Fatima Yousaf; Zain Ul Abedeen; Fatima Sajjad; Kashif Yousaf; Fizza Kazmi; Rubab Zahra; Ishfaq Ali; Sahil Kumar; Tanzeela Gul; Zartasha Rahim; Abdul Basit; Manal Sharif; Anum Noor; Habib Ur Rehman; Imdad Ullah Shah; Abdullah Afridi

doi:10.1002/joa3.70464

Key result

Catheter ablation cuts all-cause mortality ~39% vs. medical therapy in AF with reduced ejection fraction.

RR 0.61
95% CI 0.51-0.71
P<0.00001
n=131,492

Why the study?

The effectiveness of catheter ablation compared with medical therapy in patients with AF and HFrEF/HFmrEF remains incompletely defined.

Does catheter ablation reduce mortality and improve cardiac function compared to conventional medical therapy in patients with atrial fibrillation and heart failure with reduced or mildly reduced ejection fraction?

Study Design

Type

Meta-Analysis (n=131,492)

Multicenter

Yes

Structured PICO

Does catheter ablation reduce mortality and improve cardiac function compared to conventional medical therapy in patients with atrial fibrillation and heart failure with reduced or mildly reduced ejection fraction?

P

Population

131,492 adults with atrial fibrillation and heart failure with reduced or mildly reduced ejection fraction (LVEF ≤ 50%) followed for 6 months to 8 years.

I

Intervention

Catheter ablation (primarily pulmonary vein isolation with or without additional lesion sets)

C

Comparator

Conventional medical therapy (pharmacological rhythm control, rate control strategies, or guideline-directed medical therapy)

O

Outcome

All-cause mortality, cardiovascular mortality, and change in left ventricular ejection fraction (LVEF)hard clinical

Main Result

Relative Risk: 0.61 (95% CI 0.51–0.71)

p-value: p=<0.00001

Catheter ablation significantly reduces all-cause and cardiovascular mortality and improves left ventricular ejection fraction compared to medical therapy in patients with atrial fibrillation and HFrEF or HFmrEF.

Limitations

Inclusion of observational studies introduces the potential for residual confounding.
One large observational cohort contributed substantially to the overall sample size and may have disproportionately influenced the pooled estimates.
Important clinical heterogeneity existed across studies, including differences in ablation strategies, procedural technologies, atrial fibrillation subtype, and baseline ventricular function.
Relatively few studies specifically enrolled patients with HFmrEF, limiting generalizability to this subgroup.
Differences in imaging modalities for LVEF assessment and variability in BNP assay methods may have introduced measurement heterogeneity.
LVEF and BNP were secondary or exploratory endpoints in most included studies rather than primary efficacy outcomes.
Substantial heterogeneity across studies for change in LVEF and cardiovascular hospitalization
Imprecision for change in BNP due to small sample size

Implication

Supports ablation over medical therapy to cut mortality in AF with HFrEF/HFmrEF; confirms benefit in largest meta-analysis to date.

Abstract

Background: Catheter ablation is an established rhythm-control strategy for atrial fibrillation (AF), but its effectiveness in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) remains incompletely defined. We performed a GRADE-assessed systematic review and meta-analysis comparing catheter ablation with conventional medical therapy in this population. Methods: PubMed, Embase, and the Cochrane Library were searched from inception to February 2026. Randomized controlled trials and observational cohort studies enrolling adults with AF and left ventricular ejection fraction (LVEF) ≤ 50% were included. Primary outcomes were all-cause mortality, cardiovascular mortality, and change in LVEF. Secondary outcomes were change in B-type natriuretic peptide (BNP) and cardiovascular hospitalization. Random-effects models were used, and certainty of evidence was assessed using GRADE. Results: Thirteen studies involving 131 492 participants were included. Catheter ablation significantly reduced all-cause mortality (RR 0.61, 95% CI 0.51-0.71) and cardiovascular mortality (RR 0.46, 95% CI 0.31-0.66), improved LVEF (MD 6.47%, 95% CI 4.47-8.47), and reduced BNP levels (MD -136.85 pg/mL, 95% CI -190.46 to -83.23). No significant reduction was observed in cardiovascular hospitalization (RR 0.78, 95% CI 0.53-1.13). Mortality benefits were consistent across subgroup analyses by study design and baseline LVEF. Conclusions: Catheter ablation was associated with lower mortality and improved cardiac function compared with medical therapy in patients with AF and HFrEF/HFmrEF. Further studies specifically evaluating HFmrEF populations are warranted.

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Published by Journal of Arrhythmia · CC BY

Cite This Study

Malik et al. (2026) conducted a meta-analysis in Atrial fibrillation with heart failure with reduced or mildly reduced ejection fraction (n=131,492). Catheter ablation vs. Conventional medical therapy was evaluated on All-cause mortality (RR 0.61, 95% CI 0.51-0.71, p=<0.00001). Catheter ablation significantly reduced all-cause mortality (RR 0.61) and cardiovascular mortality (RR 0.46) compared with medical therapy in patients with atrial fibrillation and HFrEF/HFmrEF.

synapsesocial.com/papers/6ac45d41e690f3ec2f530116 https://doi.org/10.1002/joa3.70464