Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis,JACC: Heart Failure

当前位置： X-MOL 学术 › JACC Heart Fail. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis
JACC: Heart Failure ( IF 10.3 ) Pub Date : 2021-08-11 , DOI: 10.1016/j.jchf.2021.05.005
Angelo Giuseppe Caponetti ₁ , Claudio Rapezzi ₂ , Christian Gagliardi ₁ , Agnese Milandri ₃ , Angela Dispenzieri ₄ , Arnt V Kristen ₅ , Jonas Wixner ₆ , Mathew S Maurer ₇ , Pablo Garcia-Pavia ₈ , Ivailo Tournev ₉ , Violaine Planté-Bordeneuve ₁₀ , Douglass Chapman ₁₁ , Leslie Amass ₁₁ ,

Affiliation

Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Italy.
Cardiological Center, University of Ferrara, Ferrara, Italy; Maria Cecilia Hospital, GVM Care and Research, Cotignola, Emilia-Romagna, Italy.
Department of Cardiology, Bentivoglio Hospital, Bentivoglio, Bologna, Italy.
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Cardiology, Angiology, Respiratory Medicine, Medical University of Heidelberg, Heidelberg, Germany.
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Columbia University College of Physicians and Surgeons, New York, New York, USA.
Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Madrid, Spain; Universidad Francisco de Vitoria, Pozuelo de Alarcon, Madrid, Spain.
Clinic of Nervous Diseases, University Hospital Aleksandrovska, Sofia, Bulgaria; Department of Neurology, Medical University, Sofia, Bulgaria; Department of Cognitive Science and Psychology, New Bulgarian University, Sofia, Bulgaria.
Department of Neurology- Amyloid Network-University Hospital Henri Mondor-Assistance Publique Hopitaux de Paris, IMRB INSERM U955 Team 10 "Biology of the Neuro-Muscular System", Créteil, France.
Pfizer, New York, New York, USA.

Objectives

Because patients with ATTRv cardiomyopathy are more likely to be male, this analysis aimed to increase information on associations between sex and genotype, phenotype, and degree of myocardial involvement in ATTRv amyloidosis.

Background

Transthyretin amyloid cardiomyopathy is a progressive, fatal disease that occurs due to accumulation of wild-type or variant (ATTRv) transthyretin amyloid fibrils in the myocardium.

Methods

The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy.

Results

There were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro–B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height).

Conclusions

In this analysis, myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males.

中文翻译：

遗传性转甲状腺素蛋白淀粉样变性中心脏受累的性别相关风险

目标

由于 ATTRv 心肌病患者更可能是男性，因此该分析旨在增加关于性别与 ATTRv 淀粉样变性的基因型、表型和心肌受累程度之间关联的信息。

背景

转甲状腺素蛋白淀粉样蛋白心肌病是一种进行性、致命的疾病，由于野生型或变体 (ATTRv) 转甲状腺素蛋白淀粉样蛋白原纤维在心肌中的积累而发生。

方法

转甲状腺素蛋白淀粉样变性结果调查 (THAOS) 是一项针对 ATTR 淀粉样变性患者和具有TTR突变的无症状携带者正在进行的全球纵向观察调查。分析了来自 THAOS 的数据（数据截止日期：2020 年 1 月 6 日），以确定 ATTRv 淀粉样变性患者和 ATTRv 淀粉样变性和心肌病患者在基因型、表型以及心脏和神经系统症状存在方面的任何性别差异。

结果

共有 2,790 名 ATTRv 淀粉样变性患者参加了 THAOS，其中男性患者更可能出现心脏受累症状和心脏表型。根据 N 端 B 型利钠肽前体、左心室 (LV) 射血分数、平均 LV 壁厚度除以高度和 LV 质量指数进行评估，具有更严重心脏疾病表现的患者男性患病率更高按高度。性别、发病年龄和基因型类别通过多变量分析确定为发生心肌病的危险因素（定义为左室隔膜厚度增加除以高度）。