Genetic Testing May Predict Future Cardiomyopathy, Heart Failure in Patients With Atrial Fibrillation

To evaluate the prognostic implications of cardiomyopathy-associated pathogenic or likely pathogenic (CMP-PLP) genetic variants in patients with atrial fibrillation (AF), researchers assessed prevalence of CMP-PLP variants and risk for incident CMP or heart failure (HF) after AF diagnosis in patients with AF and early-onset AF.

“Patients with atrial fibrillation (AF), a common morbid arrhythmia, are more likely to carry rare genetic variants associated with inherited cardiomyopathies,” the researchers noted. The results were published in JAMA Cardiology.

The two studies included were from the UK Biobank (UKB; data from 2006-2023; n=393,768) and the All of Us Research Program (AllofUs; data from 2018-2022; n=193,232). The researchers also assessed joint contributions of CMP-PLP variants, clinical risk, and polygenic risk.

In the UKB cohort, 32,281 participants (8%) had AF (mean age, 62 years; 20,459 [63.4%] male), and in the AllofUs cohort, 11,901 participants (6%) had AF (mean age, 67 years; 6,576 [55.3%]) male. CMP-PLP variants were found to be twice as prevalent in individuals with AF: 2.04% in the UKB cohort (95% CI, 1.89%-2.20%) and 2.52% in the AllofUs cohort (95% CI, 2.25%-2.82%).

Among patients in whom AF began before the age of 45 years, these variants were five times more prevalent: 4.99% in the UKB cohort (95% CI, 3.07%-7.91%) and 4.66% in the AllofUs cohort (95% CI, 3.40%-6.32%). The cumulative incidence of CMP or HF was significantly higher in patients with AF (18%) compared with those without AF (3%).

Among patients with AF who had no history of CMP or HF (UKB, 20,226; AllofUs, 8,330), the presence of a CMP-PLP variant was linked to a 1.6-fold increased risk of developing CMP or HF (meta-analysis, 95% CI, 1.32-1.90). Moreover, CMP-PLP variants, a polygenic risk score, and traditional clinical risk factors were each independently predictive of CMP or 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,” the researchers concluded.

Reference

Wijdeveld LFJM, et al. JAMA Cardiol. Published online April 30, 2025. doi:10.1001/jamacardio.2025.0460