耐力运动可促使携带致病性桥粒斑珠蛋白（DSP）变体的个体发生心肌损伤。

Endurance exercise promotes episodes of myocardial injury in individuals with a pathogenic desmoplakin (DSP) variant.

作者信息

Jacobsen Alan P, Chiampas Katia, Muller Steven A, Gasperetti Alessio, Yanek Lisa R, Carrick Richard T, Gordon Catherine, Tichnell Crystal, Murray Brittney, Calkins Hugh, Barouch Lili A, James Cynthia A

机构信息

Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland; Division of Cardiology, Department of Medicine, University of Utah, Salt Lake City, Utah.

Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.

出版信息

Heart Rhythm. 2024 Dec 30. doi: 10.1016/j.hrthm.2024.12.035.

DOI:10.1016/j.hrthm.2024.12.035

PMID:39742986

Abstract

BACKGROUND

Desmoplakin (DSP) variants are associated with left predominant or biventricular arrhythmogenic cardiomyopathy. Exercise promotes penetrance and sustained ventricular arrhythmias (VAs) in right-sided arrhythmogenic right ventricular cardiomyopathy, but its effect is unknown in DSP variant carriers.

OBJECTIVE

The purpose of this study was to assess whether exercise is associated with clinical outcomes in individuals with a pathogenic or likely pathogenic DSP variant.

METHODS

Adults with a pathogenic or likely pathogenic DSP variant were interviewed about physical activity from age 10. Endurance athletes were defined on the basis of a mean exercise dose >24 metabolic equivalent hours per week of moderate- to vigorous-intensity exercise. Lifetime survival free of VA (ventricular tachycardia/fibrillation or appropriate implantable cardioverter-defibrillator therapy), clinical heart failure (HF) (presentation to the emergency department or hospitalization with HF), and myocardial injury events characteristic of DSP cardiomyopathy (symptoms, elevated troponin, and imaging with nonobstructive coronaries) were examined using the Kaplan-Meier method and Cox regression models.

RESULTS

Participants (N=100; 66% female; mean age 36 ± 15 years) were active with a median 28.4 (interquartile range 14.8-46) metabolic equivalent hours per week of pre-baseline evaluation exercise, and just 8 individuals continued athlete-level exercise post-baseline evaluation. In multivariable analyses, endurance athletes (60%) had no worse survival free of VA (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.5-1.98) or clinical HF (HR 0.86; 95% CI 0.36-2.05) but their risk of myocardial injury was elevated (HR 2.37; 95% CI 1.11-5.05). Furthermore, myocardial injury episodes were strongly associated with an elevated risk of both VA (HR 7.86; 95% CI 3.56-17.33) and clinical HF (HR 10.28; 95% CI 2.95-35.83) thereafter.

CONCLUSION

Endurance exercise may promote progression of DSP cardiomyopathy by increasing the risk of myocardial injury episodes, but the effect on VA and clinical HF is less clear. This study informs shared decision-making exercise and sport participation discussions.

摘要

背景

桥粒斑蛋白（DSP）变异与左心优势型或双心室致心律失常性心肌病相关。运动可促进右心室致心律失常性心肌病患者的疾病外显率及持续性室性心律失常（VA）的发生，但其对DSP变异携带者的影响尚不清楚。

目的

本研究旨在评估运动是否与携带致病性或可能致病性DSP变异的个体的临床结局相关。

方法

对携带致病性或可能致病性DSP变异的成年人进行访谈，了解其10岁以来的体力活动情况。耐力运动员的定义为平均运动剂量>24代谢当量小时/周的中度至剧烈强度运动。采用Kaplan-Meier法和Cox回归模型，对无VA（室性心动过速/心室颤动或适当的植入式心律转复除颤器治疗）、临床心力衰竭（HF）（因HF就诊于急诊科或住院）以及DSP心肌病特征性心肌损伤事件（症状、肌钙蛋白升高以及非阻塞性冠状动脉成像）的终生生存率进行了研究。

结果

参与者（N = 100；66%为女性；平均年龄36±15岁）在基线前评估时每周的运动代谢当量中位数为28.4（四分位数间距14.8 - 46），基线后评估时仅有8人继续进行运动员水平的运动。在多变量分析中，耐力运动员（60%）无VA（风险比[HR] 1.00；95%置信区间[CI] 0.5 - 1.98）或临床HF（HR 0.86；95% CI 0.36 - 2.05）的生存率并无更差，但他们发生心肌损伤的风险升高（HR 2.37；95% CI 1.11 - 5.05）。此外，心肌损伤事件与随后发生VA（HR 7.86；95% CI 3.56 - 17.33）和临床HF（HR 10.28；95% CI 2.95 - 35.83）的风险显著相关。