Therapy Duration and Improvement of Ventricular Function in HF

Quick Takes

  • In a prospective, observational study of participants with an LVEF ≤35% undergoing continuous medication titration, 46% of participants with a persistently low LVEF at 90 days experienced improvement to >35% by day 180.
  • Between days 90 and 180, no sustained ventricular arrhythmias occurred in participants with ongoing use of their wearable cardioverter-defibrillator.

Study Questions:

To what extent does left ventricular ejection fraction (LVEF) improve beyond 90 days in patients with de novo heart failure with reduced ejection fraction (HFrEF)?


HF-OPT (Heart Failure Optimization Study) was a prospective, multicenter observational study. Patients with de novo HFrEF with LVEF ≤35% were enrolled into a 90-day registry phase during which time they received a wearable cardioverter-defibrillator (WCD) and underwent optimization of guideline-directed medical therapies (GDMT) for HF at the discretion of their treating clinician. After 90 days, participants who wore the WCD for 90 days entered into a study phase, which lasted until day 360. LVEF was measured at 0, 90, 180, and 360 days after WCD start. The primary endpoint was the proportion of participants with an improvement in LVEF to >35% between days 90 and 180.


A total of 1,300 participants enrolled into the registry and 598 advanced to the study phase (27% female, median LVEF 23%, 58% nonischemic cardiomyopathy). During the study phase, only participants with LVEFs at the first three time points were analyzed (n = 487). At day 90, 46% of participants had an LVEF >35%. This increased to 68% by day 180 and 77% by day 360 (for the 392 participants with data at 360 days). In a multivariable analysis, LVEF improvement to >35% was not associated with HF etiology. Rates of GDMT were high overall with beta-blockers, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker/angiotensin receptor–neprilysin inhibitor (ARNI), and mineralocorticoid antagonists prescribed in 97%, 94%, and 62% of participants at day 180, respectively. Being on target doses of all three drug classes at day 180 (9% of cohort) was associated with LVEF improvement to >35% (p = 0.048). During the first 90 days, 24 of 1,300 participants (1.8%) experienced 34 ventricular tachycardia (VT)/ventricular fibrillation events. Between days 90 and 180, a nonsustained VT event was observed in one WCD carrier.


In a cohort of participants who wore a WCD for 90 days and who underwent continuous optimization of GDMT, 46% of participants with a persistently low LVEF at 90 days experienced improvement to >35% by day 180 with low rates of ventricular arrhythmias beyond 90 days for those with ongoing WCD use.


This prospective, observational study demonstrated significant ongoing improvements in LVEF to >35% between days 90 and 180 in a cohort of patients undergoing continuous medication optimization. Improvement in LVEF to >35% was highest in patients on optimal doses of GDMT, and rates of ventricular arrhythmias were low for those patients with ongoing WCD use beyond 90 days. These provocative data provide further motivation for expedited GDMT titration and the need for critical resources to support safe and rapid titration. While rates of ventricular arrhythmias were low beyond 90 days, this only pertains to those participants with ongoing WCD use, excluding those with an implanted implantable cardioverter-defibrillator (ICD). Overall, these data are thought-provoking and suggest that delayed ICD implantation may be reasonable in selected patients who are unable to undergo GDMT titration early after their diagnosis with HFrEF.

The study has important limitations, however. GDMT titration in clinical studies does not necessarily reflect real-world practice, and participants were required to be compliant with WCD use for ≥90 days prior to enrollment. Furthermore, in current practice, increases in ARNI and sodium-glucose cotransporter-2 inhibitor prescribing may accelerate the timeline for LVEF improvement. Thus, in summary, the study suggests delayed ICD implantation may be reasonable for select patients to allow for further LVEF improvement, though it speaks to the need for further investment in processes for GDMT titration and for a tailored approach to HF care.

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: Heart Failure, Reduced Ejection Fraction, Wearable Electronic Devices

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