Association of Multiple Nonhypertrophic Cardiomyopathy–Related Genetic Variants and Outcomes in Patients With Hypertrophic Cardiomyopathy

IF 10.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure Pub Date : 2024-12-01 DOI:10.1016/j.jchf.2024.08.005

Takashi Hiruma MD , Shunsuke Inoue MD, PhD , Zhehao Dai MD, PhD, MPH , Seitaro Nomura MD, PhD , Toru Kubo MD, PhD , Kenta Sugiura MD, PhD , Atsushi Suzuki MD, PhD , Takeshi Kashimura MD, PhD , Shouji Matsushima MD, PhD , Takanobu Yamada MD, PhD , Takashige Tobita MD, PhD , Manami Katoh MD, PhD , Toshiyuki Ko MD, PhD , Masamichi Ito MD, PhD , Junichi Ishida MD, PhD , Eisuke Amiya MD, PhD , Masaru Hatano MD, PhD , Norifumi Takeda MD, PhD , Eiki Takimoto MD, PhD , Hiroshi Akazawa MD, PhD , Issei Komuro MD, PhD

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引用次数: 0

Abstract

Background

Approximately 10% of hypertrophic cardiomyopathy (HCM) patients have left ventricular systolic dysfunction (end-stage HCM) leading to severe heart-failure; however, risk stratification to identify patients at risk of progressing to end-stage HCM remains insufficient.

Objectives

In this study, the authors sought to elucidate whether the coexistence of other cardiovascular disease (CVD)–related variants is associated with progression to end-stage HCM in patients with HCM harboring pathogenic or likely pathogenic (P/LP) sarcomeric variants.

Methods

The authors performed genetic analysis of 83 CVD-related genes in HCM patients from a Japanese multicenter cohort. P/LP variants in 8 major sarcomeric genes (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL2, MYL3, and ACTC1) definitive for HCM were defined as “sarcomeric variants.” In addition, P/LP variants associated with other CVDs, such as dilated cardiomyopathy and arrhythmogenic cardiomyopathy, were referred to as “other CVD-related variants.”

Results

Among 394 HCM patients, 139 carried P/LP sarcomeric variants: 11 (7.9%) carried other CVD-related variants, 6 (4.3%) multiple sarcomeric variants, and 122 (87.8%) single sarcomeric variants. In a multivariable Cox regression analysis, presence of multiple sarcomeric variants (adjusted HR [aHR]: 3.35 [95% CI: 1.25-8.95]; P = 0.016) and coexistence of other CVD-related variants (aHR: 2.80 [95% CI: 1.16-6.78]; P = 0.022) were independently associated with progression to end-stage HCM. Coexisting other CVD-related variants were also associated with heart failure events (aHR: 2.75 [95% CI: 1.27-5.94]; P = 0.010).

Conclusions

Approximately 8% of sarcomeric HCM patients carried other CVD-related variants, which were associated with progression to end-stage HCM and heart failure events. Comprehensive surveillance of CVD-related variants within sarcomeric HCM patients contributes to risk stratification and understanding of mechanisms underlying end-stage HCM.

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肥厚型心肌病患者多种非肥厚型心肌病相关基因变异与预后的关系

背景：约有 10% 的肥厚型心肌病（HCM）患者会出现左心室收缩功能障碍（终末期 HCM），导致严重心力衰竭；然而，用于识别有进展至终末期 HCM 风险的患者的风险分层仍然不足：在这项研究中，作者试图阐明在携带致病性或可能致病性（P/LP）肉瘤变异的 HCM 患者中，其他心血管疾病（CVD）相关变异的共存是否与 HCM 进展到终末期有关：作者对来自日本多中心队列的 HCM 患者的 83 个心血管疾病相关基因进行了遗传分析。8个主要肉瘤基因（MYBPC3、MYH7、TNNT2、TNNI3、TPM1、MYL2、MYL3 和 ACTC1）中与 HCM 相关的 P/LP 变异被定义为 "肉瘤变异"。此外，与其他心血管疾病（如扩张型心肌病和心律失常性心肌病）相关的 P/LP 变异被称为 "其他心血管疾病相关变异"：在 394 名 HCM 患者中，有 139 人携带 P/LP 肉粒变异体：11例（7.9%）携带其他心血管疾病相关变异，6例（4.3%）携带多种肉瘤变异，122例（87.8%）携带单一肉瘤变异。在多变量 Cox 回归分析中，存在多个肉瘤变异体（调整 HR [aHR]：3.35 [95% CI：1.25-8.95]；P = 0.016）和共存其他心血管疾病相关变异体（aHR：2.80 [95% CI：1.16-6.78]；P = 0.022）与进展为终末期 HCM 独立相关。同时存在的其他心血管疾病相关变异也与心力衰竭事件有关（aHR：2.75 [95% CI：1.27-5.94]；P = 0.010）：结论：约 8% 的肉芽肿型 HCM 患者携带其他心血管疾病相关变异，这些变异与 HCM 进展到终末期和心衰事件有关。全面监测肉瘤型 HCM 患者的心血管疾病相关变异有助于进行风险分层和了解终末期 HCM 的发病机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JACC. Heart failure CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

21.20

自引率

2.30%

发文量

164

期刊介绍： JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.