Genetic Link Found Between Early-Onset AF and Risk of Cardiomyopathy or Heart Failure: Study

Results In the UKB cohort, 32 281 participants (8%) had AF (mean [SD] age, 62 [6] years; 20 459 male [63.4%]). In the AllofUs cohort, 11 901 participants (6%) had AF (mean [SD] age, 67 [12] years; 6576 male [55.3%]). Compared with the biobank populations, CMP-PLP variants were twice as prevalent in patients with AF (UKB, 2.04%; 95% CI, 1.89%-2.20%; AllofUs, 2.52%; 95% CI, 2.25%-2.82%) and 5 times as prevalent in AF with onset before age 45 years (UKB, 4.99%; 95% CI, 3.07%-7.91%; AllofUs, 4.66%; 3.40%-6.32%). Cumulative incidence of CMP/HF was high in patients with AF (18%) compared with patients without AF (3%). Still, among patients with AF without prior CMP/HF (UKB, 20 226; AllofUs, 8330), carrying a CMP-PLP variant was associated with 1.6-fold risk of incident CMP/HF (meta-analysis, 95% CI, 1.32-1.90). Finally, CMP-PLP variants, a polygenic score, and clinical risk factors were independent estimators of CMP/HF. Results of this cohort study suggest that the prevalence of CMP-PLP variants was substantial in patients with early-onset AF. Patients with AF carrying a CMP-PLP variant had an associated increased risk of future CMP/HF, independent of clinical and polygenic risk. These results indicate that genetic testing in patients with AF may identify individuals at higher risk for developing CMP/HF.

Reference:

Wijdeveld LFJM, Ajufo E, Challa SP, et al. Cardiomyopathy-Associated Gene Variants in Atrial Fibrillation. JAMA Cardiol. Published online April 30, 2025. doi:10.1001/jamacardio.2025.0460