Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.
Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.
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DOI：
10.1161/jaha.122.028973
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发表时间：
2023-08
影响因子：
5.4
通讯作者：
Ruberg, Frederick L.
中科院分区：
文献类型：
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作者：
Madhani, Avni;Sabogal, Natalia;Massillon, Daniel;Paul, Ludwine D.;Rodriguez, Carlos;Fine, Denise;Helmke, Stephen;Winburn, Morgan;Kurian, Damian;Raiszadeh, Farbod;Teruya, Sergio;Cohn, Elizabeth;Einstein, Andrew J.;Miller, Edward J.;Connors, Lawreen H.;Maurer, Mathew S.;Ruberg, Frederick L.
甲状腺素运载蛋白淀粉样心肌病（ATTR-CM）是≥60岁患者心力衰竭（HF）的一种未被诊断的原因。虽然与遗传性ATTR-CM相关的V122 I（甲状腺素运载蛋白122位的缬氨酸到异亮氨酸取代）变体存在于美国3.4%的自我认定的黑人个体（或150万人）中，但表型突变率尚不清楚。SCAN‐MP（在少数人群中使用核成像筛查心脏淀粉样变性）研究是一项目前正在进行的前瞻性多中心研究，旨在使用锝-99 m-焦磷酸盐成像确定老年（≥60岁）自认为患有HF的黑人和西班牙裔个体中ATTR‐CM的患病率。计算V122 I等位基因的频率和患病率，沿着功能、生化和超声心动图参数的分析，对SCAN-MP中的前278名黑人参与者进行。ATTR-CM的患病率为6.8%（95% CI，4.2-10.5; n=19例），其中63%为ATTR野生型。V122 I的患病率为6.5%（n=18名携带者），其中7名携带ATTR‐CM，表型突变率为39%（95% CI，17-64）。V122 I携带者ATTR-CM比未携带者表现出更严重的HF。前白蛋白浓度在具有ATTR-CM的V122 I携带者（12.9 mg/dL）中最低，而在没有ATTR-CM的携带者（21.0 mg/dL）和HF对照（25.0 mg/dL，P<0.0001）中最低。在患有HF和左心室壁厚度增加的老年黑人个体中，ATTR-CM患者中，63%为野生型，而V122 I患者中，ATTR-CM的表型突变率为39%（95%CI，17-64），表明单独的基因型不足以诊断。前白蛋白浓度可能有助于用ATTR-CM鉴定V122 I携带者。URL：https://www.clinicaltrials.gov;唯一标识符：NCT 03812172。
Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an underdiagnosed cause of heart failure (HF) among patients ≥60 years of age. Although the V122I (valine to isoleucine substitution at position 122 of the transthyretin protein) variant associated with hereditary ATTR‐CM is present in 3.4% of self‐identified Black individuals in the United States (or 1.5 million people), the phenotypic penetrance is not known. The SCAN‐MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) study is a currently accruing prospective multisite study designed to determine the prevalence of ATTR‐CM using technetium‐99m‐pyrophosphate imaging in older (≥60 years of age) self‐identified Black and Hispanic individuals with HF. Calculations of the penetrance and prevalence of the V122I allele, along with analyses of functional, biochemical, and echocardiographic parameters, were performed for the first 278 Black participants in SCAN‐MP. The prevalence of ATTR‐CM was 6.8% (95% CI, 4.2–10.5; n=19 cases), of whom 63% were ATTR wild‐type. The prevalence of V122I was 6.5% (n=18 carriers), of whom 7 had ATTR‐CM, yielding a phenotypic penetrance of 39% (95% CI, 17–64). V122I carriers with ATTR‐CM evidenced more advanced HF than carriers without ATTR‐CM. Prealbumin concentration was lowest among V122I carriers with ATTR‐CM (12.9 mg/dL) versus carriers without ATTR‐CM (21.0 mg/dL) and HF controls (25.0 mg/dL, P<0.0001). Among older Black individuals with HF and increased left ventricular wall thickness, of those with ATTR‐CM, 63% had wild‐type, and of those with V122I, the phenotypic penetrance of ATTR‐CM was 39% (95% CI, 17–64), suggesting that genotype alone is insufficient for diagnosis. Prealbumin concentration may be useful to identify V122I carriers with ATTR‐CM. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03812172.