Diagnostic and prognostic value of exercise-induced ventricular arrhythmias in genetic dilated cardiomyopathy
N Kalf, M W Tanck, E Poel, T Potekhina, M Van den Boogaard, F W Asselbergs, A A Wilde, A S AminAbstract
Background and Aims
The clinical relevance of premature ventricular contractions (PVCs) and non-sustained ventricular tachycardia (NSVT) during exercise stress testing (EST) in patients with genetic dilated cardiomyopathy (DCM) is unknown. It is particularly unclear whether these arrhythmias represent early manifestations of disease, reflect a more advanced phenotype, or provide prognostic information.
Methods
We conducted a retrospective single-center cohort study in adults with a (likely-)pathogenic variant in a DCM-associated gene who underwent an EST. Associations between ≥1 PVC or NSVT occurring during exercise or recovery phases, baseline clinical characteristics, structural abnormalities on transthoracic echocardiography or cardiac magnetic resonance imaging, and clinical outcomes were assessed using multivariable regression models. Clinical outcomes comprised: (1) sudden cardiac death or malignant ventricular arrhythmias, (2) DCM progression, and (3) initiation or intensification of heart-failure therapy or device implantation.
Results
A total of 294 patients were included, of whom 74% relatives and 56% asymptomatic at baseline. PVC/NSVT during EST occurred in 163 patients (55%) and were independently associated with age (OR 1.024; P=0.027) and late gadolinium enhancement on cardiac magnetic resonance imaging (OR 3.698; P=0.002). During a median follow-up of 70 months, patients with PVC/NSVT more often reached the composite outcome than those without (79.7% vs. 48.2%; P<0.001). In multivariable Cox regression analyses, PVC/NSVT during EST were independently associated with the composite outcome (P<0.001), with consistent associations across individual outcomes. These associations were also observed in relatives and patients who were asymptomatic at baseline. PVCs and NSVT were both prognostically relevant, with stronger associations observed for NSVT.
Conclusion
In genetic DCM, PVC or NSVT during EST are associated with myocardial fibrosis at baseline and adverse clinical outcomes during follow-up. EST provides complementary information for diagnostic evaluation and risk stratification in patients with genetic DCM, including those without overt phenotype.Multivariable Cox Hazard regressionKaplan-Meier curve