Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiovascular diseases, with a prevalence between 1:200 and 1:500, affecting more than 20 million people worldwide [1]. Although the majority (∼75%) of HCM patients have normal life expectancy without limiting symptoms, the natural history of the disease includes ominous events such as atrial fibrillation and stroke, infective endocarditis, heart failure (HF) to the worst scenario represented by sudden cardiac death (SCD). HF can develop over time mainly through three different phenotypes: left ventricular (LV) obstruction (obstructive HCM), non-obstructive HCM with a normal or preserved ejection fraction (LVEF), “end-stage” HCM or hypokinetic-dilated evolution (ES-HCM) [1].The major determinants of the most ominous outcomes, namely, all-cause death, SCD, hospitalization for HF, and HF progression, have been largely researched and studied over time and only partially identified and characterized. To date, the role o