Earlyonset atrial fibrillation in patients with cardiomyopathy: clinical and genetic structure and impact on prognosis
https://doi.org/10.15829/1728-8800-2025-4522
EDN: NZVYAU
Abstract
Aim. To study the genotype and phenotype cardiomyopathy profile with atrial fibrillation (AF), as well as to evaluate the clinical outcomes and prognostic significance of genotyping early manifestations of AF in patients with dilated cardiomyopathy (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC).
Material and methods. The study included 220 genotyped patients with cardiomyopathy as follows: 186 patients with DCM — 127 (68,3%) men, aged 44 [34; 55] years, left ventricular ejection fraction (LVEF) 30 [25; 36]%; 34 patients with NDLVC — 23 (67,6%) men, aged 35 [32; 41] years, LVEF 53 [47; 60]%. The follow-up period was 7 years with Me of 85 [69; 202] months. The cohorts were compared for the incidence of early-onset AF (at age <45 years), the genetic profile of cardiomyopathy, and clinical outcomes.
Results. Early-onset AF (paroxysmal, persistent, or permanent) was registered in 48 patients aged 35,3±6,8 years, while late-onset AF — in 33 individuals aged 53,2±3,7 years. Pathogenic variants in the LMNA, TTN, and SCN5A genes, identified in 19 (54,3%) patients, accounted for more than half of all genotypes with early-onset AF. In the laminopathy cohort (n=19), the prevalence of early-onset AF phenotype was the highest and amounted to 52,6%. Among all patients with early-onset AF, the prevalence of LMNA mutations was 20,8%; loss-of-function TTN variants were detected in 12,5%. The probability of detecting a cardiomyopathy-related variant was highest (odds ratio (OR) 17,4; 95% confidence interval (CI): 4,49-69,1) in individuals with early AF diagnosed at the age of <34 years with a family history of cardiomyopathy, and lowest in those >50 years old (χ2=30,2; p<0,001). Multivariate Cox regression analysis revealed that early AF with the pathogenic cardiomyopathy genotype was an independent predictor of cardiovascular death (hazard ratio (HR) 2,11; 95% CI: 1,09-4,07; p=0,027).
Conclusion. Variants in the LMNA, TTN, and SCN5A genes predominate in patients with genetic cardiomyopathy and early AF. Significant associations were found between genotype-positive cardiomyopathy with early-onset AF and unfavorable outcomes.
About the Authors
T. G. Vaykhanskaya
Republican Scientific and Practical Center of Cardiology
Belarus
Belarus
Rosa Luxemburg St., 110B, Minsk, 220036
T. T. Gevorkyan
Republican Scientific and Practical Center of Cardiology
Belarus
Belarus
Rosa Luxemburg St., 110B, Minsk, 220036
O. D. Levdansky
Institute of Genetics and Cytology
Belarus
Belarus
Akademicheskaya St., 27, Minsk
T. M. Koptyukh
Republican Scientific and Practical Center of Cardiology
Belarus
Belarus
Rosa Luxemburg St., 110B, Minsk, 220036
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Supplementary files
What is already known about the subject?
- Atrial fibrillation (AF) in cardiomyopathy is determined by multiple mechanisms associated with the genetic substrate, epigenomic, and population risk factors.
- The addition of AF to cardiomyopathy worsens the disease prognosis with an increased risk of death and hospitalization for stroke and heart failure.
What might this study add?
- A decrease in survival was demonstrated in patients with early AF, first recorded at age <45 years. Early development of AF in genotype-positive patients with cardiomyopathy (dilated cardiomyopathy/non-dilated cardiomyopathy) is associated with a 2-fold increased risk of cardiovascular death.
- Titin‐truncating variants (TTNtv), lamin A/C gene (LMNA) mutations, and pathogenic variants in the major sodium channel Na V1.5 gene (SCN5A) are associated with early-onset AF and cardiomyopathy.
- A cardiomyopathy genetic risk score has been developed for personalized risk stratification as an alternative tool for selecting patients with a high expected probability of a positive genotyping result.
Review
For citations:
Vaykhanskaya T.G., Gevorkyan T.T., Levdansky O.D., Koptyukh T.M. Earlyonset atrial fibrillation in patients with cardiomyopathy: clinical and genetic structure and impact on prognosis. Cardiovascular Therapy and Prevention. 2025;24(9):4522. (In Russ.) https://doi.org/10.15829/1728-8800-2025-4522. EDN: NZVYAU
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