Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction
Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction
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DOI：
10.1093/eurheartj/ehv338
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发表时间：
2015-10-07
影响因子：
39.3
通讯作者：
Garcia-Pavia, Pablo
中科院分区：
文献类型：
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作者：
Gonzalez-Lopez, Esther;Gallego-Delgado, Maria;Garcia-Pavia, Pablo
射血分数保留性心力衰竭（HFpEF）是一种异质性的临床综合征，有多种潜在原因。野生型甲状腺素运载蛋白（TTR）淀粉样变性（ATTRwt）是HFpEF的一种未被诊断的原因，可能受益于新的特异性治疗。Tc 99 m-DPD显像可无创性诊断ATTRwt。我们试图确定ATTRwt在因HFpEF.Methods和结果而入院的老年患者中的患病率，我们前瞻性筛选了所有因HFpEF [左心室（LV）射血分数>= 50%]而入院的≥ 60岁且LV肥大（>= 12 mm）的连续患者。所有符合条件的患者均行Tc-99 m-DPD脑显像。该研究纳入了120例HFpEF患者（59%为女性，82 ± 8岁）。共有16名患者（13.3%; 95%置信区间：7.2-19.5）在Tc-99 m-DPD放射性成像上显示中度至重度摄取。所有扫描阳性的患者都进行了TTR基因检测，没有发现突变。4例患者进行了肌内膜活检，所有病例都证实了ATTRwt。ATTRwt患者与其他HFpEF形式患者在年龄、性别、高血压、糖尿病、冠状动脉疾病或房颤方面无差异。虽然ATTRwt患者的N末端脑钠肽前体中位数（6467 vs. 3173 pg/L; P = 0.019），中位肌钙蛋白I（0.135 vs. 0.025 μ g/L; P < 0.001），平均LV最大壁厚（17 +/- 3.4 vs. 14 +/- 2.5 mm; P = 0.001），心包积液率（44 vs. 19%; P = 0.047），以及起搏器使用率（44 vs. 12%; P = 0.004），ATTRwt和其他HFpEF形式之间的临床重叠率高。结论ATTRwt是一种未被诊断的疾病，占HFpEF病例的显著数量（13%）。应在这些患者中评估新兴TTR修饰药物的效果。
Aims Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes. Wild-type transthyretin (TTR) amyloidosis (ATTRwt) is an underdiagnosed cause of HFpEF that might benefit from new specific treatments. ATTRwt can be diagnosed non-invasively by Tc-99m-3,3-diphosphono-1,2-propanodicar-boxylic acid (Tc-99m-DPD) scintigraphy. We sought to determine the prevalence of ATTRwt among elderly patients admitted due to HFpEF.Methods and results We prospectively screened all consecutive patients >= 60 years old admitted due to HFpEF [ left ventricular (LV) ejection fraction >= 50%] with LV hypertrophy (>= 12 mm). All eligible patientswere offered a Tc-99m-DPD scintigraphy. The study included 120 HFpEF patients (59% women, 82 +/- 8 years). A total of 16 patients (13.3%; 95% confidence interval: 7.2-19.5) showed a moderate-to-severe uptake on the Tc-99m-DPD scintigraphy. All patients with a positive scan underwent genetic testing of the TTR gene, and no mutations were found. An endomyocardial biopsy was performed in four patients, confirming ATTRwt inall cases. There were no differences in age, gender, hypertension, diabetes, coronary artery disease, or atrial fibrillation between ATTRwt patients and patients with other HFpEF forms. Although patients with ATTRwt exhibited higher median N-terminal pro-brain natriuretic peptide (6467 vs. 3173 pg/L; P = 0.019), median troponin I (0.135 vs. 0.025 mu g/L; P < 0.001), mean LV maximal wall thickness (17 +/- 3.4 vs. 14 +/- 2.5 mm; P = 0.001), rate of pericardial effusion (44 vs. 19%; P = 0.047), and rate of pacemakers (44 vs. 12%; P = 0.004), clinical overlap between ATTRwt and other HFpEF forms was high.Conclusion ATTRwt is an underdiagnosed disease that accounts for a significant number (13%) of HFpEF cases. The effect of emerging TTR-modifying drugs should be evaluated in these patients.