The Timing for Primary Prevention for ICD in the Current Era of Pharmacotherapy.

Recent advances in the pharmacological therapy of heart failure with reduced ejection fraction (HFrEF) have significantly impacted the overall survival, heart failure hospitalisations and rates of sudden cardiac death (SCD). In this context, the relevant timing of placing ICDs as primary prevention is a matter of on-going debate. This manuscript provides evidence for an updated view regarding the timing of implanting ICD in eligible patients with HFrEF receiving optimal guideline-directed medical therapy, accounting for the timing to reverse cardiac remodelling (RCR) occurrence and residual SCD risks over time. Clinically significant RCR occurs beyond 3 months of optimal guideline-directed medical therapy, while the residual risks of SCDs remain low for certain HFrEF populations. However, when deciding on ICD implantation, one should always consider individual modulators of RCR and SCD risks, as well as the non-competing risks of death that can affect patients' overall outcomes. Risk stratification algorithms need to be developed and validated in future pragmatic clinical trials to further define better timing for the use of ICDs in primary prevention.