Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS).
Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS).
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DOI：
10.1093/eurheartj/ehz173
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发表时间：
2022-02-03
影响因子：
39.3
通讯作者：
THAOS Investigators
中科院分区：
文献类型：
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作者：
Damy T;Kristen AV;Suhr OB;Maurer MS;Planté-Bordeneuve V;Yu CR;Ong ML;Coelho T;Rapezzi C;THAOS Investigators
甲状腺素运载蛋白淀粉样变性（ATTR淀粉样变性）是一种异质性疾病，具有心脏、神经和混合表型。我们描述了这种疾病在西欧大陆的表型和基因型概况，因为它出现在甲状腺素运载蛋白淀粉样变性调查（THAOS）。THAOS是一项正在进行的全球性纵向观察性调查，旨在研究ATTR淀粉样变性受试者在临床表现、诊断和自然史方面的差异。在数据截止时，来自9个西欧大陆国家的1411例症状性受试者入组THAOS [1286例遗传性（ATTRm）淀粉样变性; 125例野生型ATTR（ATTRwt）淀粉样变性]。基因型和表型因国家而异。四种突变（Val 122 Ile、Leu 111 Met、Thr 60 Ala和Ile 68 Leu）和ATTRwt与主要心脏表型相关，显示对称性左心室（LV）肥大、正常舒张期LV尺寸和容积以及轻度降低的LV射血分数（LVEF）。与混合型（n = 298）相比，心脏病患者（n = 210）超声心动图的形态和功能异常明显更严重，表型：室间隔厚度中位数（Q1-Q3）更高[18（16-21）vs. 16（13-20）mm; P = 0.0006]; LVEF <50%的发生率更高（38.1vs.17.5%，P = 0.0008）。具有心脏突变或ATTRwt（或心脏或混合表型）的受试者的生存率低于其他基因型（或神经表型）类别的受试者（P < 0.0001，两者均为）。ATTR淀粉样变性基因型和表型在西欧大陆是高度异质性的。不同疾病特征的地理分布图和对一部分受试者具有显性心脏表型（模仿肥厚型心肌病）的认识，有助于临床识别这种诊断不足的疾病。ClinicalTrials.gov：NCT 00628745。
Transthyretin amyloidosis (ATTR amyloidosis) is a heterogeneous disorder with cardiac, neurologic, and mixed phenotypes. We describe the phenotypic and genotypic profiles of this disease in continental Western Europe as it appears from the Transthyretin Amyloidosis Survey (THAOS). THAOS is an ongoing, worldwide, longitudinal, observational survey established to study differences in presentation, diagnosis, and natural history in ATTR amyloidosis subjects. At data cut-off, 1411 symptomatic subjects from nine continental Western European countries were enrolled in THAOS [1286 hereditary (ATTRm) amyloidosis; 125 wild-type ATTR (ATTRwt) amyloidosis]. Genotypes and phenotypes varied notably by country. Four mutations (Val122Ile, Leu111Met, Thr60Ala, and Ile68Leu), and ATTRwt, were associated with a mainly cardiac phenotype showing symmetric left ventricular (LV) hypertrophy, normal diastolic LV dimensions and volume, and mildly depressed LV ejection fraction (LVEF). Morphologic and functional abnormalities on echocardiogram were significantly more severe in subjects with cardiac (n‘= 210), compared with a mixed (n = 298), phenotype: higher median (Q1–Q3) interventricular septal thickness [18 (16–21) vs. 16 (13–20) mm; P = 0.0006]; and more frequent incidence of LVEF <50% (38.1 vs. 17.5%; P = 0.0008). Subjects with cardiac mutations or ATTRwt (or cardiac or mixed phenotype) had a lower survival rate than subjects in other genotype (or the neurologic phenotype) categories (P < 0.0001, for both). ATTR amyloidosis genotypes and phenotypes are highly heterogeneous in continental Western Europe. A geographic map of the different disease profiles and awareness that a subset of subjects have a dominant cardiac phenotype, mimicking hypertrophic cardiomyopathy, at presentation can facilitate the clinical recognition of this underdiagnosed disease. ClinicalTrials.gov: NCT00628745.