A new review is calling for a re-examination of the “sustained and indefinite” use of guideline-directed medical therapy (GDMT) in patients with heart failure accompanied by improved ejection fraction (HFimpEF). The review assesses the Withdrawal of Pharmacological Treatment for Heart Failure in Patients with Recovered Dilated Cardiomyopathy (TRED-HF) trial. This investigation specifically looked at the effects of withdrawing GDMT in patients with dilated cardiomyopathy who had achieved complete left ventricular ejection fraction (LVEF) recovery. While the trial found that nearly 40% of patients experienced relapse within six months, the researchers noted that many relapses were asymptomatic and reversible upon reinitiation of therapy. Yet, they emphasized the caution warranted in clinical practice. “…This trial demonstrates that routine withdrawal of GDMT in patients with dilated cardiomyopathy (DCM) and recovered LVEF should currently be avoided unless necessary,” said Nandan Kodur from Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Ohio, and W.H. Wilson Tang, MD, from the Cleveland Clinic. Underlying etiology Published online in JACC: Heart Failure, the researchers also discussed the heterogeneous nature of HFimpEF. They pointed out that the underlying etiology, such as idiopathic, familial or chemotherapy-induced cardiomyopathy, played a critical role in determining prognosis and response to treatment de-escalation. Imaging techniques such as cardiac magnetic resonance (CMR) with T1 mapping and measurements like global longitudinal strain, alongside biomarkers such as NT-proBNP adjusted for body mass index, could help identify patients who may safely reduce their medication burden. While some observational studies and small trials theorized that limited de-escalation of GDMT may prove safe in some low-risk patients, the authors said that there were currently insufficient data to support routine de-escalation of GDMT at this time. They called for large-scale, randomized controlled trials with long-term follow-up to better define which patients could benefit from a tailored approach to therapy. HFimpEF definition HFimpEF is defined by an absolute improvement in left ventricular ejection fraction (LVEF) by at least 10% to over 40%, It is generally associated with a better prognosis compared to persistent heart failure with reduced ejection fraction. Despite improvements in cardiac function, patients are advised to stay on the treatment. “Current guidelines recommend sustained and indefinite treatment of HFimpEF due to concerns of relapse,” concluded Kodur and Tang. Sources: Kodur N, Tang WHW. Management of Heart Failure With Improved Ejection Fraction: Current Evidence and Controversies. JACC: Heart Fail. 2025; 13:537–553. Image Credit: Yeti Studio – stock.adobe.com