Why the study?
Guidelines recommend ICD implantation after at least 3 months of GDMT in heart failure patients with LVEF ≤35%, but contemporary GDMT may improve LVEF beyond 3 months.
Does extending GDMT (including ARNI) beyond 3 months improve LVEF to >35% and reduce primary prevention ICD eligibility in patients with HFrEF?
Systematic Review (n=1,703)
Does extending GDMT (including ARNI) beyond 3 months improve LVEF to >35% and reduce primary prevention ICD eligibility in patients with HFrEF?
Extending optimized GDMT for an additional 3 to 6 months beyond current 3-month guideline recommendations leads to significant LVEF recovery in 21-59% of patients, safely avoiding unnecessary ICD implantations.
Objective Guidelines recommend an implantable cardioverter-defibrillator (ICD) in patients with heart failure and a left ventricular ejection fraction (LVEF) of 35% or less despite at least 3 months of guideline-directed medical therapy (GDMT) to reduce the risk of sudden cardiac death (SCD). However, more efficacious contemporary GDMT may be associated with improvements in LVEF beyond 3 months.Methods A systematic review of MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Trials, the Cochrane Database of Systematic Reviews and Web of Science was conducted. Studies of patients with an LVEF of 35% or less after at least 3 months of GDMT who were treated with a longer duration of GDMT were included. Risk of bias was evaluated using the Newcastle-Ottawa Scale and a narrative synthesis presented. We report rates of LVEF improvement to above the 35% threshold and all-cause mortality after longer-duration GDMT.Results Sixteen observational studies met the inclusion criteria. Risk of bias identified in six of these studies was mainly related to adequacy of follow-up. Risk of bias across other domains and in the other studies was low. Four studies reported the temporal change in ICD eligibility. Following 3–6 months additional GDMT, there was an improvement in LVEF to above 35% in 21%–59% of participants. Three studies reported higher proportions of participants with an LVEF above 35% with increasing duration of GDMT. Seven studies reported all-cause mortality, ranging from 0% to 7.6% during follow-up of 6–24 months.Conclusion In patients with heart failure and an LVEF of 35% or less despite at least 3 months of GDMT, two to six in 10 patients demonstrated an improvement in their LVEF to >35% after a further 3–6 months of GDMT. During this period, mortality rates were low. A longer period of GDMT prior to evaluation for ICD may be appropriate.PROSPERO registration number CRD42023390835.
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Whittaker et al. (2026) conducted a systematic review in Heart failure with reduced ejection fraction (HFrEF) and LVEF ≤35% despite ≥3 months of GDMT (n=1,703). Longer duration guideline-directed medical therapy (including ARNI) vs. Baseline (single-cohort comparisons) was evaluated on Proportion of patients in whom there was an increase in LVEF to >35% (21%-59% improvement to >35% LVEF).
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