Outcome in Phospholamban R14del Carriers: Results of a Large Multicentre Cohort Study
Background—The pathogenic phospholamban (PLN) R14del mutation causes dilated and/or arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of PLN R14del mutation carriers.
Methods and Results—Using the family tree mortality ratio method in a cohort of 403 PLN R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval (CI): 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias, and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, while for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction < 45% and sustained or non-sustained ventricular tachycardia with hazard ratios of 4.0 (95% CI: 1.9-8.1) and 2.6 (95% CI: 1.5-4.5), respectively.
Conclusions—PLN R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction < 45% and sustained or non-sustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is therefore advised from adolescence onwards.
- arrhythmogenic cardiomyopathy
- dilated cardiomyopathy
- ventricular arrhythmia
- arrhythmogenic right ventricular dysplasia/cardiomyopathy
- Received October 10, 2013.
- Revision received April 24, 2014.
- Accepted May 8, 2014.