Background: Wild-type transthyretin amyloidosis (ATTRwt), an underappreciated cause of heart failure in older adults, is challenging to diagnose and monitor in the absence of validated, disease-specific biomarkers. We examined the prognostic use and survival association of serum TTR (transthyretin) concentration in ATTRwt.

Methods and Results: Patients with biopsy-proven ATTRwt were retrospectively identified. Serum TTR, cardiac biomarkers, and echocardiographic parameters were assessed at baseline and follow-up evaluations. Statistical analyses included Kaplan–Meier method, Cox proportional hazard survival models, and receiver-operating characteristic curve analysis. Median serum TTR concentration at presentation was 23 mg/dL (n=116). Multivariate predictors of shorter overall survival were decreased TTR, left ventricular ejection fraction and elevated cTn-I (cardiac troponin I); an inclusive model demonstrated superior accuracy in 4-year survival prediction by receiver-operating characteristic curve analysis (area under the curve, 0.77). TTR values lower than the normal limit, <18 mg/dL, were associated with shorter survival (2.8 versus 4.1 years; P=0.03). Further, TTR values at 1- and 2-year follow-ups were significantly lower (P<0.001) in untreated patients (n=23) compared with those treated with TTR stabilizer, diflunisal (n=12), after baseline evaluation. During 2-year follow-up, unchanged TTR corresponded to increased cTn-I (P=0.006) in untreated patients; conversely, the diflunisal-treated group showed increased TTR (P=0.001) and stabilized cTn-I and left ventricular ejection fraction at 1 year.

Conclusions: In this series of biopsy-proven ATTRwt, lower baseline serum TTR concentration was associated with shorter survival as an independent predictor of outcome. Longitudinal analysis demonstrated that decreasing TTR corresponded to worsening cardiac function. These data suggest that TTR may be a useful prognostic marker and predictor of outcome in ATTRwt.

背景：野生型运甲状腺素蛋白淀粉样变性（ATTRwt）是老年人心力衰竭的一种未被充分认识的病因，在缺乏经过验证的，针对疾病的生物标记物的情况下，诊断和监测具有挑战性。我们检查了ATTRwt中血清TTR（运甲状腺素蛋白）浓度的预后用途和生存关联。

方法和结果：回顾性鉴定经活检证实的ATTRwt的患者。在基线和随访评估中评估血清TTR，心脏生物标志物和超声心动图参数。统计分析包括Kaplan–Meier方法，Cox比例风险生存模型和接收者操作特征曲线分析。出现时的血清TTR浓度中位数为23 mg / dL（n = 116）。总生存期缩短的多因素预测指标是TTR降低，左心室射血分数和cTn-I（心肌肌钙蛋白I）升高。包含模型通过接收者操作特征曲线分析（曲线下面积0.77）证明了4年生存预测的卓越准确性。TTR值低于正常限值（<18 mg / dL）与较短的生存期相关（2.8年与4.1年；P= 0.03）。此外，在基线评估后，未接受治疗的患者（n = 23）与未接受治疗的患者（n = 23）相比，在1年和2年随访中的TTR值显着降低（P <0.001）。在2年的随访中，未治疗的患者的TTR不变对应cTn-I升高（P = 0.006）。相反地​​，在1年时，二氟乙醛治疗组显示TTR增加（P = 0.001），并且cTn-I和左心室射血分数稳定。

结论：在这一系列经活检证实的ATTRwt中，较低的基线血清TTR浓度与较短的生存期相关，这是预后的独立预测指标。纵向分析表明，TTR降低与心脏功能恶化相对应。这些数据表明，TTR可能是ATTRwt中有用的预后标志物和预后指标。