Clinical scenarios of HCM-related mortality: relevance of age and stage of disease at presentation

In the early days, Hypertrophic cardiomyopathy (HCM) has long been considered a malignant disease.

However, contemporary descriptions of HCM report low mortality rates, largely due to heart failure-related complications (HF), while sudden cardiac death (SCD) rates are consistently low. Ageing with HCM is not uncommon and competing risk of acquired cardiovascular (CV) and non-CV diseases becomes relevant over time.

To describe the disease stage at presentation and the modes of death in a cohort of consecutive HCM patients followed at a national referral centre over the last two decades. Stages of disease were defined according to Circ. Heart Fail. 2012, as follows:

1) “Classic HCM phenotype” characterized by LV ejection fraction (EF) >65%.

2) “Adverse remodeling” characterized by LVEF in the range of 50% to 65%.

3) “Overt dysfunction” is the end-stage clinical evolution characterized by a LVEF <50%.

By searching our centralized database, we identified 1491 HCM patients with at least >1 year of follow-up between January 2000 and December 2020, 191 of whom died in the same period. In 30 the cause of death could not be ascertained. The remaining 161 constituted our study cohort.

Of the 161 patients who died, 103 (64%) died due to HCM-related causes, whereas 58 (36%) died from non-HCM-related causes such as coronary artery disease (other CV) or other non CV causes.

Modes of death varied based on the stage of disease at diagnosis:

– Fifty-six (35%) patients had a “classic” HCM phenotype at diagnosis. Of these, about half died of HCM-related causes (n=30; 54%), versus 45% with non-HCM-related death. Differently from the other 2 stages, the single most common cause of death was “other non-CV related” mortality, in 44%. Among HCM-related causes, SCD prevailed (n=15; 27%) while HF-related events were only 8 (14%).

– Of the 86 (53%) patients with “adverse remodeling” at diagnosis, more than half died of HCM-related causes (n=57, 66%), largely due to HF (n=33, 38%); SCD occurred in 18 (21%) individuals. This stage included the highest percentage of patients who died of stroke (n=6; 7%).

– Of the 19 (12%) patients in “overt dysfunction” at diagnosis, HF represented the cause of demise in almost three quarters (n=14, 74%); SCD and non-HCM causes accounted for only 10% and 16% respectively.

Most HCM patients die due to complications of their own disease, mainly in the context of HF. Modes of death vary with the stage of disease, with SCD becoming less prevalent in more advanced phases of progression, when competitive risks of HF-related events become overwhelming. These data highlight an unmet medical need in the prevention of disease progression associated with HCM.

Type of funding sources: None.