Abstract
Segan et al. report that 90% of patients with atrial fibrillation- mediated cardiomyopathy (AFCM) maintained left ventricular ejection fraction (LVEF) ≥50% af ter withdrawing heart failure therapy following successful rhythm control.1 While these results challenge the current practice of indefinite guideline-directed medical therapy (GDMT) in patients with improved ejection fraction, two important questions remain before these findings can be applied more broadly: which patients are appropriate candidates for withdrawal, and how should they be monitored?
The trial excluded patients with coronary disease, structural heart disease, and AF duration exceeding one year. This approach reveals a fundamental challenge, distinguishing pure AFCM from AF coexisting with other cardiomyopathies. AFCM is diagnosed primarily through exclusion as cardiac imaging alone cannot definitively differentiate etiologies.2
In routine practice, many patients have mixed etiologies. It may be difficult to exclude underlying structural disease from concurrent arrhythmia-induced dysfunction. The TRED-HF trial in dilated cardiomyopathy showed 40% relapse rates within six months of medication withdrawal, suggesting that etiology matters considerably.3 In contrast, emerging evidence shows LVEF in tachycardia-induced cardiomyopathy typically improves within 4 to 12 weeks of arrhythmia eradication, suggesting rhythm control as the primary driver of recovery.2 It seems that withdrawal should be considered only in patients meeting strict criteria. This entails absence of coronary or structural heart disease, absence of myocardial fibrosis as noted on cardiac MRI, LVEF normalization temporally linked to rhythm control, and sustained sinus rhythm after withdrawal. Even then, 10% of WITHDRAW-AF patients did not maintain LVEF ≥50% after withdrawal, underscoring the need for caution.
The WITHDRAW-AF protocol relied heavily on Cardiac Magnetic Resonance imaging (CMR) both for initial screening to exclude structural heart disease and for serial follow-up assessments at 6 and 12 months. While CMR is the gold standard for LVEF quantification and tissue characterization, this presents a significant barrier to implementation in routine practice. Not only is CMR a costly test, but availability remains limited with long wait times at many centers. In addition, approximately 3-4% of patients cannot tolerate the exam due to claustrophobia or body habitus.4 Patients with certain implantable devices may not be candidates for CMR, further limiting its accessibility.
WITHDRAW-AF showed that patients with pure AFCM and sustained rhythm control may safely discontinue heart failure therapy. However, the highly specific target population population and resource intensive screening and monitoring limit immediate generalizability. Until further studies develop, GDMT withdrawal should be considered only in exceptional cases of confirmed pure AFCM with sustained sinus rhythm, absence of other cardiac disease and equipped for close surveillance.
Recommended Citation
Zhang, MD, David
(2026)
"Commentary on the WITHDRAWAL-AF Trial and its Applicability in Select Patient Populations,"
The Medicine Forum: Vol. 27, Article 13.
Available at:
https://jdc.jefferson.edu/tmf/vol27/iss1/13
