Lifetime Clinical Course of Hypertrophic Cardiomyopathy: Outcome of the Historical Florence Cohort Over 5 Decades.

The current understanding of the clinical course and long-term outcome of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with relatively short follow-up, usually <10 years. Extended assessments more closely reflecting HCM lifetime burden are not available. The purpose of this study was to report the lifetime clinical course of HCM. We analyzed the clinical course of HCM patients diagnosed at our center from 1970 to 1992 and followed annually to the present. Cumulative incidence functions were used to estimate the incidence of HCM-related mortality (including heart failure [HF]/stroke related, sudden cardiac death [SCD]) and non-HCM related. A total of 202 patients (age 41 ± 17 years; 63% male) were followed 27 ± 6 [range: 3-50] years. Overall, 97 (48%) survived and 105 (52%) died during the particularly long follow-up; 69 deaths were related to HCM, including 53 HF related, 11 fatal embolic strokes, and 16 SCDs. Annual overall HCM-related mortality was 1.3%/y, increasing from 0.7% during the first decade to 1.8% in the second/third decade ( In this unique HCM cohort followed for up to 50 years, often before contemporary therapies became widely implemented for HCM, HF frequently progressed over time, while arrhythmic SCD events were less common and remained constant over time. Despite spanning different management eras over 5 decades, HCM-related mortality remained relatively low (1.3%/y).

© 2023 The Authors.

Dr Olivotto was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement no. 777204: “SILICOFCM - In Silico trials for drug tracing the effects of sarcomeric protein mutations leading to familial cardiomyopathy”; has received grants from 10.13039/100002491Bristol Myers Squibb, 10.13039/100014941Cytokinetics, 10.13039/100015362Amicus, 10.13039/100004329Genzyme, 10.13039/100007343Shire, 10.13039/100004326Bayer, 10.13039/100008497Boston Scientific, Menarini International; fees (honoraria or consulting) from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire, and Boston Scientific; and served or currently serving as PI on EXPLORER-HCM, MAVA-LTE, REDWOOD-HCM, REDWOOD-OLE, and SEQUOIA-HCM trial. Dr M. S. Maron is a consultant for Cytokinetics and Steering Committee Chair for REDWOOD-HCM phase 2 trial; consultant for Imbria Pharmaceuticals; and is a consultant and has a research grant from 10.13039/100007723Takeda Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN PATIENT CARE: Current understanding of the clinical course and long-term outcome of patients with HCM has been extrapolated from cohorts with relatively short follow-up, usually <10 years. In this unique HCM cohort followed for up to 50 years, often before contemporary therapies became widely implemented for HCM, annual overall HCM-related mortality was 1.3%/y, increasing from 0.7% during the first decade to 1.8% in the second/third decade, mainly driven by increase in HF-/stroke-related events (from 0.6% to 1.3%). However, sudden death mortality rate was similar during the 2 periods (0.1% vs 0.44%). TRANSLATIONAL OUTLOOK: These data support the recognition that contemporary management options can substantially impact mortality directly attributable to HCM. Indeed, >40% of our patients would have benefited importantly by treatment options not fully available >20 years ago.