Genotype influences the risk and age of onset of atrial fibrillation in patients with dilated cardiomyopathy
D Cannie, A Bakalakos, A Protonotarios, M Lorenzini, O Guttmann, C O'Mahony, K Savvatis, N Sekhri, S Mohiddin, L Lopes, P Syrris, P M ElliottAbstract
Introduction
More than 25% of patients with dilated cardiomyopathy (DCM) have disease caused by dominantly inherited genetic variants.1
Purpose
Assess the impact of genotype on the risk and age-of-onset of atrial fibrillation and flutter (AF) in patients with DCM.
Methods
Consecutive and clinically-affected variant-carriers from the 3 most prevalent DCM genotypes in a database from a cardiomyopathy unit (TTN, DSP and LMNA) were retrospectively recruited. Consecutive DCM patients returning no pathogenic or likely pathogenic variants from a next generation DCM panel were recruited for comparison (genotype-negative group). Demographics and baseline characteristics were collected and the incidence and age-of-onset of AF was compared between genotypes.
Results
Longitudinal data were available for 493 patients from 445 families (311 (63.1%) males, presenting at a median [IQR] age of 50.8 years [37.3 – 59.8]; Table 1). At last evaluation, the prevalence of AF was highest in LMNA (57.1%) and TTN (35.8%) variant-carriers and there was a significant difference between genotypes (chi-squared p value < 0.001 and Figure 1). In a multivariable Cox model including age, sex and proband status, having a LMNA variant was independently associated with an increased hazard of AF (HR 3.0 [1.7 – 5.0], p value < 0.001) and genotype-negative status with a decreased hazard (HR 0.67 [0.46 – 0.99], p = 0.04).
Conclusions
AF is common in variant-carriers of genes associated with DCM and the incidence and age of onset of AF varies by genotype. Regular ambulatory monitoring is important to detect AF, particularly in LMNA variant-carriers.