TY - JOUR
T1 - Outcome in phospholamban R14del carriers results of a large multicentre cohort study
AU - Van Rijsingen, Ingrid A.W.
AU - Van Der Zwaag, Paul A.
AU - Groeneweg, Judith A.
AU - Nannenberg, Eline A.
AU - Jongbloed, Jan D.H.
AU - Zwinderman, Aeilko H.
AU - Pinto, Yigal M.
AU - Lekanne Dit Deprez, Ronald H.
AU - Post, Jan G.
AU - Tan, Hanno L.
AU - De Boer, Rudolf A.
AU - Hauer, Richard N.W.
AU - Christiaans, Imke
AU - Van Den Berg, Maarten P.
AU - Van Tintelen, J. Peter
AU - Wilde, Arthur A.M.
N1 - Publisher Copyright:
© 2014 American Heart Association, Inc.
PY - 2014/6/8
Y1 - 2014/6/8
N2 - Background: The pathogenic phospholamban R14del mutation causes dilated and 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 phospholamban R14del mutation carriers. Methods and Results: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 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, whereas 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 nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. Conclusions: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and endstage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained 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.
AB - Background: The pathogenic phospholamban R14del mutation causes dilated and 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 phospholamban R14del mutation carriers. Methods and Results: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 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, whereas 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 nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. Conclusions: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and endstage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained 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.
UR - http://www.scopus.com/inward/record.url?scp=84914176677&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.113.000374
DO - 10.1161/CIRCGENETICS.113.000374
M3 - Article
C2 - 24909667
AN - SCOPUS:84914176677
SN - 1942-325X
VL - 7
SP - 455
EP - 465
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 4
ER -