van Rijsingen Ingrid A W, van der Zwaag Paul A, Groeneweg Judith A, Nannenberg Eline A, Jongbloed Jan D H, Zwinderman Aeilko H, Pinto Yigal M, Dit Deprez Ronald H Lekanne, Post Jan G, Tan Hanno L, de Boer Rudolf A, Hauer Richard N W, Christiaans Imke, van den Berg Maarten P, van Tintelen J Peter, Wilde Arthur A M
Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of Cardiology (J.A.G., R.N.W.H.) and Genetics (J.G.P.), University Medical Center Utrecht, Utrecht, The Netherlands.
Circ Cardiovasc Genet. 2014 Aug;7(4):455-65. doi: 10.1161/CIRCGENETICS.113.000374. Epub 2014 Jun 8.
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.
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.
Phospholamban 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 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.
致病性磷酸受纳蛋白R14del突变可导致扩张型和致心律失常性右室心肌病，并与恶性室性心律失常和终末期心力衰竭风险增加相关。我们开展了一项多中心研究，以评估磷酸受纳蛋白R14del突变携带者队列中的死亡率、心脏疾病结局以及恶性室性心律失常的危险因素。
在一个包含403名磷酸受纳蛋白R14del突变携带者的队列中，采用家系死亡率比方法，我们发现标准化死亡率比为1.7（95%置信区间为1.4 - 2.0），从25岁起死亡率显著过高。有295名携带者可获得心脏学数据。在中位随访期42个月时，55名（19%）个体首次发生恶性室性心律失常，33名（11%）发生终末期心力衰竭事件。发生恶性室性心律失常的最小年龄为20岁，而终末期心力衰竭事件为31岁。恶性室性心律失常的独立危险因素为左室射血分数<45%以及持续性或非持续性室性心动过速，风险比分别为4.0（95%置信区间为1.9 - 8.1）和2.6（95%置信区间为1.5 - 4.5）。
磷酸受纳蛋白R14del突变携带者发生恶性室性心律失常和终末期心力衰竭的风险很高，左室射血分数<45%以及持续性或非持续性室性心动过速为独立危险因素。从青春期后期起死亡率高且预后不良。因此，建议从青春期开始进行基因和心脏筛查。
