Heart Failure Patients Unresponsive to Implantable Cardioverter-Defibrillator Therapy: A Neglected Problem

After publication of the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial,1 a debate has arisen in the cardiologists' community on the clinical benefit of implantable cardioverter-defibrillator (ICD) in the modern therapy of non-ischaemic heart failure (HF) patients,2 selected according to the current ICD guideline recommendations (i.e. ejection fraction value and HF functional class).3 The DANISH trial is a recent large randomized controlled trial that compared ICD therapy vs. optimal medical treatment in patients with non-ischaemic cardiomyopathy, and reported no mortality benefit of ICD therapy.1 In support of the current guidelines, recent meta-analyses showed instead a statistically significant clinical efficacy of ICD therapy by pooling DANISH results with those of the earlier studies carried out in the 2000s.4 In this debate, little attention has been paid to the different factors concurring to ICD clinical benefit and to their evolution over time. The clinical benefit of ICD therapy in patients with HF and low ejection fraction is mainly determined by: (i) the baseline risk of total mortality, cardiac death, and sudden cardiac death (SCD); (ii) the percentage of ICD-unresponsive patients (i.e. patients experiencing SCD despite ICD implantation). In particular, the unresponsiveness of patients to ICD therapy and its detrimental effects on ICD clinical benefit are a crucial, but fairly neglected problem.5