Key result
Thin filament sarcomeric variant carriers had a significantly worse prognosis for heart failure progression or death (HR 7.9, 95% CI 1.3-47.5, p=0.024) in a Russian HCM cohort with 2.86%/year mortality.
Why the study?
Ethnic groups underrepresented in HCM studies may have distinctive characteristics, motivating an evaluation of the clinical and genetic landscape of Russian HCM patients.
Cohort (n=193)
No
Answers are grounded in this paper and cite their sources.
This Russian HCM cohort study reveals a 38% genetic yield with a potential founder effect for MYBPC3 p.Q1233, worse heart failure prognosis in thin filament variant carriers, and highlights a critically low ICD implantation rate (5.7%) alongside a relatively high all-cause mortality rate (2.86%/year).
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), and 21% had septal reduction therapy. A sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3), and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63, and FLNC. Thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p = 0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; and family studies on some rare variants enriched worldwide knowledge in HCM.
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Чумакова et al. (2023) conducted a cohort in Hypertrophic cardiomyopathy (HCM) (n=193). Thin filament sarcomeric gene variants (TPM1, TNNT2, TNNI3, TNNC1, ACTC1) vs. Other genotype-positive HCM patients without thin filament variants was evaluated on Heart failure outcome (new HF progression or death from HF) (HR 7.9, 95% CI 1.3-47.5, p=0.024). Thin filament sarcomeric variant carriers had a significantly worse prognosis for heart failure progression or death (HR 7.9, 95% CI 1.3-47.5, p=0.024) in a Russian HCM cohort with 2.86%/year mortality.
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