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期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2024.0442

摘要内容如下：

重要性

甲状腺素运载蛋白（ATTR）蛋白引起的系统性淀粉样变性是引起心肌病的最常见的淀粉样变性类型。

观察

甲状腺素运载蛋白（TTR）蛋白转运甲状腺素（甲状腺激素）和视黄醇（维生素A），主要由肝脏合成。当TTR蛋白错误折叠时，它会形成淀粉样纤维，沉积在心脏中，导致心力衰竭、心脏传导阻滞或心律失常（如房颤）。淀粉样纤维形成的生物学过程尚不完全清楚，但与衰老有关，在一些患者中，受TTR基因序列遗传变异的影响。ATTR淀粉样变性是由错误折叠的TTR蛋白沉积引起的。ATTR可与正常TTR遗传序列（野生型ATTR）或异常TTR遗传序列（变异型ATTR）相关。野生型ATTR主要表现为心肌病，而由遗传变异引起的ATTR则表现为心肌病和/或多发性神经病。在美国，大约有50，000至150，000人因ATTR淀粉样变性而患有心力衰竭。如果不进行治疗，ATTR淀粉样变性导致的心力衰竭的中位生存期约为5年。在TTR中存在超过130种不同的遗传变异。最常见的遗传变异是Val122Ile（PV142I），这是一种起源于西非国家的等位基因，存在于美国3.4%的非洲裔美国人或大约150万人中。诊断可以使用血清游离轻链测定和免疫固定电泳来排除轻链淀粉样变性，并结合心脏核闪烁扫描来检测放射性示踪剂摄取，其模式与淀粉样变性一致。loop利尿剂，如呋塞米、托拉塞米和布美他尼，是治疗ATTR心力衰竭患者液体超负荷和缓解症状的主要药物。与安慰剂相比，抑制TTR蛋白错误折叠的ATTR定向治疗（Tafamidis，一种蛋白稳定剂）将死亡率从42.9%降至29.5%，将住院率从0.7/年降至0.48/年，并且在病程早期给药时最有效。

结论和相关性

在美国，ATTR淀粉样变性导致大约15万人患有心肌病，而Tafamidis是目前唯一批准的治疗药物。与安慰剂相比，在ATTR相关心肌病患者中，Tafamidis减缓了ATTR淀粉样变性的进展，提高了生存率，避免了住院。

英文原文如下：

Abstracts

Importance  Systemic amyloidosis from transthyretin (ATTR) protein is the most common type of amyloidosis that causes cardiomyopathy.

Observations  Transthyretin (TTR) protein transports thyroxine (thyroid hormone) and retinol (vitamin A) and is synthesized predominantly by the liver. When the TTR protein misfolds, it can form amyloid fibrils that deposit in the heart causing heart failure, heart conduction block, or arrhythmia such as atrial fibrillation. The biological processes by which amyloid fibrils form are incompletely understood but are associated with aging and, in some patients, affected by inherited variants in the TTR genetic sequence. ATTR amyloidosis results from misfolded TTR protein deposition. ATTR can occur in association with normal TTR genetic sequence (wild-type ATTR) or with abnormal TTR genetic sequence (variant ATTR). Wild-type ATTR primarily manifests as cardiomyopathy while ATTR due to a genetic variant manifests as cardiomyopathy and/or polyneuropathy. Approximately 50 000 to 150 000 people in the US have heart failure due to ATTR amyloidosis. Without treatment, heart failure due to ATTR amyloidosis is associated with a median survival of approximately 5 years. More than 130 different inherited genetic variants in TTR exist. The most common genetic variant is Val122Ile (pV142I), an allele with an origin in West African countries, that is present in 3.4% of African American individuals in the US or approximately 1.5 million persons. The diagnosis can be made using serum free light chain assay and immunofixation electrophoresis to exclude light chain amyloidosis combined with cardiac nuclear scintigraphy to detect radiotracer uptake in a pattern consistent with amyloidosis. Loop diuretics, such as furosemide, torsemide, and bumetanide, are the primary treatment for fluid overload and symptomatic relief of patients with ATTR heart failure. An ATTR-directed therapy that inhibited misfolding of the TTR protein (tafamidis, a protein stabilizer), compared with placebo, reduced mortality from 42.9% to 29.5%, reduced hospitalizations from 0.7/year to 0.48/year, and was most effective when administered early in disease course.

Conclusions and Relevance  ATTR amyloidosis causes cardiomyopathy in up to approximately 150 000 people in the US and tafamidis is the only currently approved therapy. Tafamidis slowed progression of ATTR amyloidosis and improved survival and prevented hospitalization, compared with placebo, in people with ATTR-associated cardiomyopathy.

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