Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias

Abstract

Background: Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (AR-DCM). We investigated the phenotype and natural history of patients with AR-DCM.

Methods and results: Two hundred eighty-five patients with a recent diagnosis of DCM (median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months). AR-DCM was defined by the presence of ≥1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (≥5 beats, ≥150 bpm), ≥1000 premature ventricular contractions/24 hours, and ≥50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (SCD), sustained ventricular tachycardia (SVT), or ventricular fibrillation (VF). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for AR-DCM phenotype. AR-DCM subjects had a higher incidence of SCD/SVT/VF compared with non-AR-DCM patients (30.3% vs 17.6%, P=0.022), with no difference in the secondary end points. A family history of SCD/SVT/VF and the AR-DCM phenotype were statistically significant and cumulative predictors of SCD/SVT/VF.

Conclusions: One-third of DCM patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow-up. A family history of ventricular arrhythmias in DCM predicts a poor prognosis and increased risk of SCD.

Keywords: arrhythmia; cardiomyopathy; prognosis; sudden death.

Figure 1

Kaplan–Meier event‐free survival. Comparison of (A) SCD/SVT/VF‐free survival (primary end point) and (B) D/HTx‐free survival (secondary end point) between AR‐DCM patients and non–AR‐DCM patients. AR‐DCM patients have a greater risk of life‐threatening arrhythmic events compared with the other DCM patients (P=0.02). Follow‐up from birth to end point/last follow‐up evaluation. Survival rates (as percentage of patients at risk) are provided at ages 25, 50, and 75 years. AR‐DCM indicates arrhythmogenic dilated cardiomyopathy; D/HTx, heart failure death (excluding SCD)/heart transplant; SCD/SVT/VF, sudden cardiac death, sustained ventricular tachycardia, and ventricular fibrillation.

Figure 2

Kaplan–Meier event‐free survival. Comparison of SCD/SVT/VF ‐free survival (primary end point) between AR‐DCM patients and non–AR‐DCM patients. With the progress of follow‐up, AR‐DCM patients have a greater risk of ventricular arrhythmic events compared with to the other DCM patients (P=0.001 at 100 months). Follow‐up from enrollment/last follow‐up evaluation. AR‐DCM indicates arrhythmogenic dilated cardiomyopathy; SCD/SVT/VF, sudden cardiac death, sustained ventricular tachycardia, and ventricular fibrillation.

Figure 3

Cox‐estimated SCD/ventricular arrhythmias–free survival stratified by 2 risk factors. Cox‐estimated SCD/SVT/VF‐free survival stratified by 2 risk factors, family history of SCD or ventricular arrhythmias and AR‐DCM diagnosis, in the overall DCM population (285 patients). The AR‐DCM phenotype (hazard ratio 1.81, 95% CI 1.10–2.97, P=0.02) and family history of SCD or ventricular arrhythmias (hazard ratio 2.21, 95% CI 1.04–4.66, P=0.038) show an additive prognostic effect on mortality for arrhythmic events. AR‐DCM indicates arrhythmogenic dilated cardiomyopathy; SCD/SVT/VF, sudden cardiac death, sustained ventricular tachycardia, and ventricular fibrillation.

Figure 4

Kaplan–Meier SCD/ventricular arrhythmias–free survival. Kaplan–Meier SCD ventricular arrhythmias–free survival stratified by AR‐DCM criteria in the AR‐DCM population (109 patients). The cumulative effect of having 1, 2, 3, or 4 AR‐DCM criteria (NSVT ≥5 beats and ≥150 bpm; PVCs ≥1000/24 h; ventricular couplets ≥50/24 hours; syncope) is not significant. AR‐DCM indicates arrhythmogenic dilated cardiomyopathy; NSVT, nonsustained ventricular tachycardia; PVCs, premature ventricular contractions; SCD/SVT/VF, sudden cardiac death, sustained ventricular tachycardia, and ventricular fibrillation.