Background: Electrocardiogram (ECG) and cardiac imaging play key roles in the diagnostic criteria for arrhythmogenic cardiomyopathy (AC), but their roles in risk stratification of patients presenting without life-threatening ventricular arrhythmia are unclear.
Purpose: To identify predictors of first-time life-threatening ventricular arrhythmia by assessing clinical characteristics, ECG and cardiac imaging in a prospective cohort study of patients with AC.
Methods: We included consecutive AC probands and mutation positive family members with no previous life-threatening arrhythmic events, and followed them prospectively from time of diagnosis. The endpoint was the first life-threatening ventricular arrhythmia, defined as aborted cardiac arrest, appropriate ICD-shock or sustained ventricular tachycardia. At baseline, we assessed possible risk predictors from three categories; (1) clinical parameters, (2) ECG and (3) cardiac imaging (echocardiography and cardiac magnetic resonance imaging) according to the Task Force Criteria of 2010. In addition to traditional imaging criteria, we assessed left ventricular (LV) and echocardiographic strain parameters. LV mechanical dispersion was defined as the standard deviation of time from onset Q/R on ECG to peak negative strain in 16 LV segments. We recorded exercise habits, and defined high intensity exercise as >6 metabolic equivalents.
Results: We included 117 patients (29% probands, 50% female, age 40±17 years). During 4.2 (IQR 2.4 to 7.4) years of follow-up, 18 (15%) patients experienced life-threatening ventricular arrhythmia. The 1, 2 and 5 year incidence was 6%, 9% and 22%, respectively. History of high intensity exercise was the strongest clinical predictor, T-wave inversions ≥V3 was the strongest ECG predictor and greater LV mechanical dispersion by echocardiography was the strongest predictor from cardiac imaging (adjusted HR; 4.9 [95% CI 1.3–18.3], p=0.02, 5.8 [95% CI 2.1–16.1], p=0.001, and 1.4 [95% CI 1.2–1.6] by 10 ms increments, p<0.001, respectively). These parameters had incremental risk predicting value (Figure, left panel). Arrhythmia free survival in patients with all three risk factors was only 1.2 (95% CI 0.4–1.9) years, compared to 17.4 (95% CI 16.6–18.2) years in patients without any risk factors (Figure, right panel).
Conclusions: History of high intensity exercise, T-wave inversions ≥V3 on ECG and greater echocardiographic LV mechanical dispersion were strong and independent predictors of life-threatening ventricular arrhythmias. AC patients without any of these risk factors had minimal arrhythmic risk, while having more than one risk factor increased the risk dramatically. This may guide decisions on primary preventive ICD implantation in these patients.