Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Parkland Health and Hospital System, Dallas, TX, USA.
Curr Heart Fail Rep. 2022 Oct;19(5):356-363. doi: 10.1007/s11897-022-00570-1. Epub 2022 Aug 5.
Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of morbidity and mortality. There remains substantial delay between initial symptoms and diagnosis. With the recent emergence of various targeted therapies proven to reduce morbidity and mortality, there is an imperative to diagnose subclinical disease. Biomarkers may be well-suited for this role.
Conventional markers of heart failure, such as natriuretic peptides and cardiac troponins, and estimated glomerular filtration rate are associated with risk in ATTR-CM. Circulating transthyretin (TTR) levels parallel TTR kinetic stability, correlate with disease severity, and may serve as indirect markers of ATTR-CM disease activity and response to targeted treatment. There is also growing evidence for the correlation of TTR to retinol-binding protein 4, a biomarker which independently associates with this disease. The rate-limiting step for ATTR pathogenesis is dissociation of the TTR homotetramer, which may be quantified using subunit exchange to allow for early risk assessment, prognostication, and assessment of treatment response. The protein species that result from the dissociation and misfolding of TTR are known as nonnative transthyretin (NNTTR). NNTTR is quantifiable via peptide probes and is a specific biomarker whose reduction is positively correlated with improvement in neuropathic ATTR amyloidosis. Neurofilament light chain (NfL) is released into the blood after axonal damage and correlates with neuropathic ATTR amyloidosis, but its clinical use in ATTR-CM is uncertain. Conventional markers of heart failure, transthyretin, retinol-binding protein 4, transthyretin kinetic stability, nonnative transthyretin, peptide probes, and neurofilament light chain have potential as biomarkers to enable early, subclinical diagnosis in patients with transthyretin cardiac amyloidosis.
转甲状腺素蛋白心脏淀粉样变（ATTR-CM）是一种浸润性心肌病，也是发病率和死亡率日益增加的原因。从最初的症状到诊断之间仍存在很大的延迟。随着最近出现的各种已被证明能降低发病率和死亡率的靶向治疗方法，诊断亚临床疾病势在必行。生物标志物可能非常适合这一角色。
心力衰竭的常规标志物，如利钠肽和心脏肌钙蛋白，以及估计的肾小球滤过率，与 ATTR-CM 的风险相关。循环转甲状腺素（TTR）水平与 TTR 动力学稳定性平行，与疾病严重程度相关，并且可以作为 ATTR-CM 疾病活动和对靶向治疗反应的间接标志物。TTR 与视黄醇结合蛋白 4 的相关性也有越来越多的证据，该生物标志物与这种疾病独立相关。ATTR 发病机制的限速步骤是 TTR 同源四聚体的解离，这可以使用亚基交换来定量，从而进行早期风险评估、预后和治疗反应评估。从 TTR 的解离和错误折叠中产生的蛋白质称为非天然转甲状腺素（NNTTR）。可以通过肽探针来定量 NNTTR，它是一种特异性生物标志物，其减少与神经病变 ATTR 淀粉样变的改善呈正相关。神经丝轻链（NfL）在轴突损伤后释放到血液中，与神经病变 ATTR 淀粉样变相关，但在 ATTR-CM 中的临床应用尚不确定。心力衰竭的常规标志物、转甲状腺素、视黄醇结合蛋白 4、转甲状腺素动力学稳定性、非天然转甲状腺素、肽探针和神经丝轻链有可能成为生物标志物，使转甲状腺素心脏淀粉样变患者能够进行早期、亚临床诊断。
