DOI: 10.1001/jamanetworkopen.2026.20145 ISSN: 2574-3805

Heart Failure Medication Withdrawal in Patients With Improved Cardiac Function After Atrial Fibrillation Ablation

Sitong Li, Yidan Sun, Yiwei Lai, Hui Wang, Jiancheng Han, Yuge Zhang, Mingyang Gao, Jue Wang, Jingrui Zhang, Liu He, Jing Cui, Xueyuan Guo, Song Zuo, Xiaoxia Liu, Nian Liu, Songnan Li, Ning Zhou, Ribo Tang, Deyong Long, Caihua Sang, Xin Du, Jianzeng Dong, Changsheng Ma

Importance

Withdrawal of guideline-directed medical therapy (GDMT) for heart failure (HF) is common after atrial fibrillation (AF) catheter ablation and recovery of cardiac function, but safety remains uncertain.

Objective

To assess the feasibility and safety of phased GDMT withdrawal in patients with AF with highly suspected AF-mediated cardiomyopathy after catheter ablation.

Design, Setting, and Participants

This open-label pilot randomized clinical trial included adult patients who were enrolled and randomized from April 13, 2023, to September 19, 2024, at Beijing Anzhen Hospital, China, with a 6-month follow-up. Eligible patients were those with suspected AF-mediated cardiomyopathy at 3 months after ablation, defined by sinus rhythm at 3 months after ablation, absence of other suspected cardiomyopathies, improvement of left ventricular ejection fraction (LVEF) from 45% or less to 55% or more, normalized LV end-diastolic diameter (LVEDD), N-terminal pro–brain natriuretic peptide (NT-proBNP) levels less than 250 ng/L, and no HF symptoms or signs.

Interventions

Patients were randomly assigned in a 1:1 ratio to phased GDMT withdrawal or GDMT continuation.

Main Outcomes and Measures

The primary end point was HF deterioration, defined as LVEF decline more than 10% to less than 55%, LVEDD increase more than 10% and beyond normal, NT-proBNP levels doubling to more than 400 ng/L, or worsening HF signs or symptoms. Secondary outcomes included cardiovascular events, changes in echocardiographic and cardiac magnetic resonance (CMR) parameters, NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) scores, atrial arrhythmia recurrence, and adverse drug events.

Results

Among 50 patients enrolled and randomized, 47 completed follow-up (median [IQR] age, 56.0 [48.0-60.5] years; 37 males [78.7%]), including 23 (48.9%) in the GDMT withdrawal group and 24 (51.1%) in the continuation group. HF deterioration occurred in 3 patients with GDMT withdrawal (13.0%) and 0 with GDMT continuation (0%) ( P  = .11). Early GDMT reinitiation in 3 patients with HF deterioration showed recovery of LVEF or NT-proBNP. No cardiovascular events occurred. Median (IQR) echocardiographic (LVEF: 0% [−3.0% to 3.5%] vs 1.5% [−5.0% to 5.0%]), CMR (LVEF: −2.1% [−7.2% to 4.6%] vs 2.9% [−2.6% to 7.4%]), and KCCQ-12 score (0 [0 to 0.5] vs 0) changes were similar between groups. Median (IQR) NT-proBNP levels declined more in the GDMT continuation group than the withdrawal group (−25.7 [−33.6 to −6.7] pg/mL vs 2.7 [−21.4 to 24.2] pg/mL; P  = .03). Adverse drug events were more frequent in the GDMT continuation group than the withdrawal group (5 [20.8%] vs 0 [0%]; P  = .050). Arrhythmia recurrence rates were comparable (GDMT withdrawal: 3 [13.0%] vs continuation: 3 [12.5%]).

Conclusions and Relevance

In this pilot randomized clinical trial of carefully selected patients with AF with normalized cardiac function and sinus rhythm after catheter ablation, 13% of patients with GDMT withdrawal experienced HF deterioration, whereas drug-related complications were more common in the continuation group, suggesting that further studies are needed to determine whether GDMT can be safely discontinued in this population.

Trial Registration

Chinese Clinical Trial Registry Identifier: ChiCTR2300077439

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