Background

A pathogenic variant in the gene encoding phospholamban (PLN), a protein that regulates calcium homeostasis of cardiomyocytes, causes PLN cardiomyopathy. It is characterized by a high arrhythmic burden and can progress to severe cardiomyopathy. Risk assessment guides implantable cardioverter-defibrillator therapy and benefits from personalization. Whether sex-specific differences in PLN cardiomyopathy exist is unknown.

Objective

The purpose of this study was to improve the accuracy of PLN cardiomyopathy diagnosis and risk assessment by investigating sex-specific aspects.

Methods

We analyzed a multicenter cohort of 933 patients (412 male, 521 female) with the PLN p.(Arg14del) pathogenic variant following up on a recently developed PLN risk model. Sex-specific differences in the incidence of risk model components were investigated: low-voltage electrocardiogram (ECG), premature ventricular contractions, negative T waves, and left ventricular ejection fraction.

Results

Sustained ventricular arrhythmias (VAs) occurred in 77 males (18.7%) and 61 females (11.7%) (P = .004). Of the 933 cohort members, 287 (31%) had ≥1 low-voltage ECG during follow-up (180 females [63%], 107 males [37%]; P = .006). Female sex, age, age at clinical presentation, and proband status predicted low-voltage ECG during follow-up (area under the curve: 0.78). Sustained VA-free survival was lowest in males with low-voltage ECG (P <.001).

Conclusion

Low-voltage ECGs predict sustained VA and are a component of the PLN risk model. Low-voltage ECGs are more common in females, yet prognostic value is greater in males. Future studies should determine the impact of this difference on the risk prediction of PLN cardiomyopathy and possibly other cardiomyopathies.

中文翻译：

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受磷蛋白心肌病的性别特异性方面：低压心电图的重要性和预后价值

背景

受磷蛋白 (PLN) 是一种调节心肌细胞钙稳态的蛋白质，编码受磷蛋白 (PLN) 基因的致病变异会导致 PLN 心肌病。它的特点是心律失常负担高，可发展为严重的心肌病。风险评估指导植入式心脏复律除颤器治疗和个性化的好处。PLN 心肌病是否存在性别特异性差异尚不清楚。

客观的

本研究的目的是通过调查性别特异性方面来提高 PLN 心肌病诊断和风险评估的准确性。

方法

我们分析了一个由 933 名患者（412 名男性，521 名女性）组成的多中心队列，其中 PLN p.(Arg14del) 致病性变异对最近开发的 PLN 风险模型进行了跟踪。研究了风险模型组件发生率的性别差异：低压心电图 (ECG)、室性早搏、负 T 波和左心室射血分数。

结果

77 名男性 (18.7%) 和 61 名女性 (11.7%) 发生持续性室性心律失常 (VAs) ( P = .004)。在 933 名队列成员中，287 名（31%）在随访期间有 ≥1 次低压心电图（180 名女性 [63%]，107 名男性 [37%]；P = .006）。女性、年龄、临床表现年龄和先证者状态可预测随访期间的低电压心电图（曲线下面积：0.78）。有低压心电图的男性持续无 VA 生存率最低（P <.001）。

结论

低压心电图可预测持续的 VA，并且是 PLN 风险模型的一个组成部分。低压心电图在女性中更常见，但在男性中的预后价值更大。未来的研究应确定这种差异对 PLN 心肌病和可能的其他心肌病风险预测的影响。