@article{Vissing:2026:10.1161/CIRCULATIONAHA.125.076036,
author = {Vissing, CR and Axelsson, Raja A and Helms, AS and Saberi, S and Owens, AT and Rossano, JW and Abrams, DJ and Ingles, J and Gray, B and Lampert, R and Stendahl, JC and Lakdawala, NK and Ware, JS and Parikh, VN and Michels, M and Crotti, L and Ryan, TD and Olivotto, I and Day, SM and Bundgaard, H and Claggett, BL and Ho, CY},
doi = {10.1161/CIRCULATIONAHA.125.076036},
journal = {Circulation},
title = {Differences in Disease Trajectory, Comorbidities, and Mortality in Sarcomeric and Nonsarcomeric Hypertrophic Cardiomyopathy.},
url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.125.076036},
year = {2026}
}

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TY  - JOUR
AB  - BACKGROUND: Sarcomere gene variants are a key cause of hypertrophic cardiomyopathy (HCM), and have been associated with worse prognosis. However, it is unclear how comorbidities influence clinical trajectories, the timing of events, and causes of death in sarcomeric and nonsarcomeric HCM. METHODS: We conducted a multicenter longitudinal cohort study of genotyped patients with HCM in the Sarcomeric Human Cardiomyopathy registry (SHaRe). Patients were classified as sarcomeric HCM (pathogenic/likely pathogenic sarcomere variant) or nonsarcomeric HCM (genetically elusive). The influence of genetic classification and comorbidities on the sequence of cardiovascular events were assessed in time-varying Cox proportional hazards models. RESULTS: Among 6120 patients (40% women; 87% probands; 50% sarcomeric HCM), followed for a median of 5.3 years, sarcomeric HCM (n=3082) was associated with a younger age at diagnosis (median 38.1 versus 54.3 years; P<0.001), a higher proportion of women and less obesity, hypertension, and left ventricular (LV) obstruction. After age standardization, sarcomeric HCM was associated with a higher burden of atrial fibrillation (age-standardized incidence [ASI] ratio, 1.28 [CI, 1.16-1.40]), LV systolic dysfunction (ASI ratio, 1.31 [CI, 1.15-1.48]), and ventricular arrhythmias (ASI ratio, 1.37 [CI, 1.17-1.52]) than nonsarcomeric HCM. All-cause mortality was similar (10.4% versus 9.4%; P=0.20); however, patients with sarcomeric HCM died younger (mean 7.8 years; P<0.001), with model-based survival-analysis estimating 3.5 life-years lost between ages 44 and 85. Sarcomeric HCM was also associated with higher HCM-related mortality (hazard ratio [HR], 1.61 [CI, 1.18-2.20]). Temporal analysis identified atrial fibrillation as the strongest disease-modifier, increasing the risk of LV systolic dysfunction (HR, 2.54 [CI 2.07-3.11]), ventricular arrhythmias (HR, 3.13 [CI, 2.36-4.20]), and mortality (HR, 1.94 [CI, 1.64-2.31]) in both groups. Genotype-inte
AU  - Vissing,CR
AU  - Axelsson,Raja A
AU  - Helms,AS
AU  - Saberi,S
AU  - Owens,AT
AU  - Rossano,JW
AU  - Abrams,DJ
AU  - Ingles,J
AU  - Gray,B
AU  - Lampert,R
AU  - Stendahl,JC
AU  - Lakdawala,NK
AU  - Ware,JS
AU  - Parikh,VN
AU  - Michels,M
AU  - Crotti,L
AU  - Ryan,TD
AU  - Olivotto,I
AU  - Day,SM
AU  - Bundgaard,H
AU  - Claggett,BL
AU  - Ho,CY
DO  - 10.1161/CIRCULATIONAHA.125.076036
PY  - 2026///
TI  - Differences in Disease Trajectory, Comorbidities, and Mortality in Sarcomeric and Nonsarcomeric Hypertrophic Cardiomyopathy.
T2  - Circulation
UR  - http://dx.doi.org/10.1161/CIRCULATIONAHA.125.076036
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41800474
ER  - 

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