Therapy duration and improvement of ventricular function in de novo heart failure: the Heart Failure Optimization study

Abstract

Background and aims: In patients with de novo heart failure with reduced ejection fraction (HFrEF), improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy. However, improvement may not be completed within 90 days.

Methods: Patients with HFrEF and LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator between 2017 and 2022 from 68 sites were enrolled, starting with a registry phase for 3 months and followed by a study phase up to 1 year. The primary endpoints were LVEF improvement > 35% between Days 90 and 180 following guideline-recommended medical therapy initiation and the percentage of target dose reached at Days 90 and 180.

Results: A total of 598 patients with de novo HFrEF [59 years (interquartile range 51-68), 27% female] entered the study phase. During the first 180 days, a significant increase in dosage of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was observed (P < .001). At Day 90, 46% [95% confidence interval (CI) 41%-50%] of study phase patients had LVEF improvement > 35%; 46% (95% CI 40%-52%) of those with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68% (95% CI 63%-72%). In 392 patients followed for 360 days, improvement > 35% was observed in 77% (95% CI 72%-81%) of the patients. Until Day 90, sustained ventricular tachyarrhythmias were observed in 24 wearable cardioverter-defibrillator carriers (1.8%). After 90 days, no sustained ventricular tachyarrhythmia occurred in wearable cardioverter-defibrillator carriers.

Conclusions: Continuous optimization of guideline-recommended medical therapy for at least 180 days in HFrEF is associated with additional LVEF improvement > 35%, allowing for better decision-making regarding preventive implantable cardioverter-defibrillator therapy.

Keywords: Guideline-recommended medical therapy; Heart failure; Wearable cardioverter-defibrillator.

Structured Graphical Abstract

Summary of design and results of Heart Failure Optimization study. Median left ventricular ejection fraction and percentage of patients with left ventricular ejection fraction > 35% at baseline, Days 90, 180, and 360. GRMT, guideline-recommended medical therapy; HFrEF, heart failure with reduced ejection fraction; LVEF, left ventricular ejection fraction; WCD, wearable cardioverter-defibrillator.

Figure 1

CONSORT flow diagram with disposition of patients in Heart Failure Optimization study. ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction

Figure 2

Scatter plots depicting paired data of left ventricular ejection fraction. (A) Index left ventricular ejection fraction vs. left ventricular ejection fraction at first follow-up visit (90 days or wearable cardioverter-defibrillator discontinuation; ‘secondary left ventricular ejection fraction’). (B) Left ventricular ejection fraction at Day 90 vs. Day 180. (C) Left ventricular ejection fraction at Day 90 vs. Day 360. (D) Left ventricular ejection fraction at Day 180 vs. Day 360. Blue dots: ‘Registry only’ patients. Orange dots: ‘Study only’ patients. Black dots: Patients with ischaemic cardiomyopathy. Red dots: Patients with non-ischaemic cardiomyopathy. LVEF, left ventricular ejection fraction

Figure 3

Sankey plot of individual changes in left ventricular ejection fraction from Day 0 to Day 360 in patients with (A) ischaemic cardiomyopathy (n = 236) and (B) non-ischaemic cardiomyopathy (n = 156). LVEF, left ventricular ejection fraction