Impact of Early Intensive GDMT on LVEF Recovery and ICD Decision Making in de Novo HFrEF

AIMS: Implantable cardioverter-defibrillator (ICD) implantation is recommended in patients with heart failure with reduced ejection fraction (HFrEF) and left ventricular ejection fraction (LVEF) ≤ 35% after 3 months of optimized medical therapy (OMT). Whether recent advances in guideline-directed medical therapy (GDMT), including angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) alter the timing of ICD implantation remains uncertain. METHODS: In this single-centre, prospective cohort study, 106 patients with newly diagnosed HFrEF (mean age 63 ± 13 years; 25% women; 53% non-ischaemic aetiology) and baseline LVEF ≤35% were enrolled between 2019 and 2022. Echocardiographic assessments were performed at baseline, 3 months and 12 months to evaluate LVEF improvement. The primary endpoint was LVEF recovery >35% between 90 days and 1 year. RESULTS: Baseline mean LVEF was 27%. At 3 months, mean LVEF increased to 37% (P < 0.001), and 58% of patients achieved LVEF >35%. These patients showed further improvement to a median LVEF of 45% at 12 months. Among those with LVEF ≤35% at 3 months (n = 44), only eight patients (18%) recovered by 12 months, six of whom received cardiac resynchronization therapy. The rapid initiation and optimization of GDMT, particularly ARNI and SGLT2i, was associated with early LVEF improvement. CONCLUSIONS: Early and intensive GDMT optimization resulted in significant LVEF improvement within the first 3 months post-diagnosis for most patients. Those who failed to recover by this point exhibited limited improvement by 1 year. These findings suggest that the conventional 3 month window for ICD decision making remains appropriate, despite advancements in heart failure therapy.