Is the clinical benefit of primary prevention implantable cardioverter-defibrillator overestimated? The role of sudden cardiac death to total mortality ratio

The commentary refers to ‘Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study’ by M. Zabel et al., 2020; doi: 10.1093/eurheartj/ehaa226. We read with great interest the results of the EU-CERT-ICD study, recently published by Zabel et al. 1 in the European Heart Journal. The study addressed the relevant issue of the clinical benefit of implantable cardioverter-defibrillator (ICD) therapy in primary prevention of sudden cardiac death (SCD) in patients with ischaemic and non-ischemic left ventricular dysfunction, under modern heart failure treatment. The results indicated a significant reduction in total mortality in ICD patients with respect to controls. We think that some comments are necessary for a broader interpretation of the study results and their implications. Some guiding principles need to be considered when assessing ICD clinical effectiveness.2 Implantable cardioverter-defibrillator therapy is efficacious only on ventricular tachyarrhythmias, while it has no effect on other forms of cardiac death related to heart failure evolution, or on non-cardiac deaths. Given the null effect of ICD on non-sudden and non-cardiac deaths, the reduction of all-cause mortality by ICD therapy cannot be superior to the reduction of SCD. The study results seem to contradict these premises. Indeed, ICD therapy determined an absolute risk reduction of 2.1% for SCD (from 2.6% to 0.5%) and of 3.7% for all-cause mortality (from 9.2% to 5.5%). The almost double effect of ICD on all-cause mortality risk with respect to SCD risk may indicate the presence of confounding factors, which may have significantly contributed to the reduction of non-sudden and non-cardiac deaths in the ICD arm or to their increase in the control arm (these mortality data are not reported in the study). In both cases, the study results may be biased towards an overestimation of ICD clinical benefit. The authors addressed this problem just partially, suggesting ‘an improved awareness and better surveillance of ICD patients’, but we think that this may not be sufficient to explain such differences in ICD effect between all-cause mortality and SCD. Of note, also the limited annualized percentage of appropriate shocks reported in the study (2.8%) and the fact that not all shocks are lifesaving3 are hardly compatible with the observed reduction (3.7%) in all-cause mortality, further suggesting an overestimation of ICD clinical benefit. Given the presence of potential confounders that may have biased the assessment of ICD benefit, we think that the results of the EU-CERT-ICD study should be interpreted with caution and not used to restrain research addressed to the improvement and refinement of ICD implantation guidelines. The subgroup analysis presented in the study goes in the direction of guidelines improvement, identifying patient subgroups (patients older than 75 years and diabetic patients) with reduced ICD benefit despite an ICD indication.1 On the other hand, studies aimed at identifying specific markers of arrhythmic risk, able to complement the ejection fraction in a poly-parametric risk assessment, should be pursued and promoted. Among risk markers, a high level of evidence supports the assessment of ventricular fibrosis by late gadolinium enhancement as a strong predictor of ventricular tachyarrhythmias treatable by ICD4 but also as stratification marker to assess the clinical benefit of ICD treatment.5 No new data were generated or analysed in support of this research. Conflict of interest: none declared.