Impact of early intensive GDMT on LVEF recovery and ICD decision making in de novo HFrEF

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.

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.

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.

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.