We have read with great interest the scientific letter by Belarte-Tornero et al.1 The introduction of the most recent pharmacological novelties in the treatment of heart failure with reduced ejection fraction, such as sacubitril-valsartan (SV), have represented a therapeutic advance, which has been shown to significantly improve the prognosis and quality of life of heart failure patients.

The authors1 conclude that a strategy providing SV before consideration of a cardiac implantable device could likely avoid the need for almost 60% of cardiac implantable devices, thus decreasing the short- and long-term associated complications and allowing for lower health care expenditure without compromising patient outcomes. These conclusions are strong but not sustained by the study design, the results obtained, or current knowledge on the risk of ventricular arrhythmias (VA) and sudden cardiac death (SCD).

Because this was a single center retrospective study, its results do not imply causality and are merely hypothesis-generating. The echocardiographic measurements of left ventricular ejection fraction (LVEF) were not performed blind in a core lab, which is a major limitation for a technique with high interobserver variability. Importantly, patients who died during SV titration were excluded, a decision that is difficult to understand since those patients could have died because they had no cardiac implantable device. Other important limitations of the study include the exclusion of high-risk patients, and those who were lost to follow-up. Finally, a mean follow-up of 16 months is too short for any study on primary prevention of SCD.

There is increasing evidence of the limitations of LVEF for arrhythmia risk stratification.2,3 In this regard, contrast-enhanced cardiac magnetic resonance (ce-CMR) has been shown to be a useful technique to improve arrhythmic risk stratification, both for ischemic and nonischemic cardiomyopathies.2,3 CMR allows detection the amount of myocardial scar and characterization of its components (core, border zone), thus permitting identification of the arrhythmogenic substrate related to the development of scar-related VA.4

A related consideration is that, because there are no randomized trials comparing the outcomes of cardiac resynchronization (CRT)-pacemakers vs CRT-defibrillators in primary prevention, prior studies5,6 have assessed the impact of the presence of myocardial scar, as analyzed by ce-CMR, on the occurrence of appropriate implantable cardiac defibrillator therapies and SCD. The presence, extent, heterogeneity, and qualitative distribution of the scar border zone independently predicted appropriate implantable cardiac defibrillator therapies and SCD in the CRT population, whereas LVEF did not, for both ischemic and nonischemic etiologies.5,6 Later, the occurrence of VA and SCD depended on the presence of myocardial scar but not on CRT response (ie, improvement of LVEF and left ventricular volume reduction).5,6 Echocardiographic response to CRT is only weakly associated with the size of the myocardial scar and is influenced by several other parameters, such as preload and afterload, autonomic factors, and medication itself.

In a similar way, the ‘echocardiographic response’ to SV therapy could incorrectly place many patients at a theoretical low risk for VA/SCD which, in many cases, may not correspond to the actual underlying risk, similarly to what was observed prospectively in CRT responders with underlying arrhythmogenic scars.5,6 In this regard, the direct measurement and characterization of the scar using ce-CMR could likely be more precise to assess the VA/SCD risk, and could improve the selection of patients suitable for ICD implantation.

Similarly, pharmacological advances will undoubtedly lead to a prognostic improvement in terms of overall mortality and hospital admissions for heart failure, but further prospective studies with longer follow-up times would still be required for accurate arrhythmia risk stratification. In our opinion, clinical decision-making based purely on echocardiographic response to SV should be avoided, and patient custom-tailored assessment of arrhythmia risk should be preferred.