Background: TTR (transthyretin) cardiac amyloidosis is caused by dissociation of TTR into monomers, which misassemble into amyloid fibrils. TTR stabilizers act at the dimer–dimer interface to prevent dissociation. We investigated differences in survival among patients with TTR cardiac amyloidosis on stabilizer medications compared with those not on stabilizers.

Methods AND RESULTS: A retrospective study of patients with TTR cardiac amyloidosis presenting to a single center was conducted. Baseline characteristics were compared between those treated with stabilizers and those not treated with stabilizers. Cox proportional hazards modeling assessed for univariate predictors of the composite outcome of death or orthotopic heart transplant (OHT). Multivariable Cox proportional hazards assessed whether stabilizer treatment was independently associated with improved death or OHT after controlling for significant univariate predictors. One hundred twenty patients (mean age, 75±8, 88% male) were included: 29 patients who received stabilizers and 91 patients who did not. Stabilizer use was associated with a lower risk of the combined end point of death or OHT (hazard ratio, 0.32; 95% confidence interval, 0.18–0.58; P<0.0001). Subjects treated with stabilizers were more likely to be of White race (93% versus 55%; P<0.001), classified as New York Heart Association classes I and II (79% versus 38%; P=0.002), less likely to have a mutation (10% versus 36%; P=0.010), have lower troponin I (median 0.06 versus 0.12 ng/mL; P=0.002), and higher left ventricular ejection fraction (49% versus 40%; P=0.011), suggesting earlier stage of disease. In multivariable Cox analysis, the association between stabilizer and death or OHT persisted when adjusted for all noncollinear univariate predictors with P<0.05 (hazard ratio, 0.37; 95% confidence interval, 0.19–0.75; P=0.003).

Conclusions: TTR stabilizers are associated with decreased death and OHT in TTR cardiac amyloidosis. These results need to be confirmed by ongoing randomized clinical trials.

背景： TTR（运甲状腺素蛋白）心脏淀粉样变性病是由于TTR分解成单体而引起的，后者会错误地组装成淀粉样蛋白原纤维。TTR稳定剂在二聚体-二聚体界面起作用，以防止解离。我们调查了使用稳定剂药物的TTR心脏淀粉样变性患者与未使用稳定剂药物的患者之间的生存差异。

方法与结果：回顾性研究了TTR心脏淀粉样变性病患者在一个中心就诊的情况。比较了用稳定剂治疗的基线特征和未用稳定剂治疗的基线特征。Cox比例风险模型评估了死亡或原位心脏移植（OHT）的复合结果的单变量预测因子。多变量Cox比例风险评估在控制了重要的单变量预测因素后，稳定剂治疗是否与死亡率或OHT的改善独立相关。其中包括120名患者（平均年龄，75±8，男性，88％）：29例接受了稳定剂的患者和91例未接受稳定剂的患者。使用稳定剂可使死亡或OHT合并终点的风险降低（危险比，0.32； 95％置信区间，0.18-0.58；P <0.0001）。用稳定剂治疗的受试者更有可能是白人种族（93％对55％；P <0.001），被归类为纽约心脏协会I级和II级（79％对38％；P = 0.002），患这种疾病的可能性较小。突变（10％对36％；P = 0.010），肌钙蛋白I较低（中位数0.06对0.12 ng / mL；P = 0.002）和较高的左心室射血分数（49％对40％；P = 0.011），提示疾病的早期阶段。在多变量Cox分析中，当对所有非共线性单变量预测因子进行校正后，P <0.05（危险比，0.37； 95％置信区间，0.19-0.75；P，P），稳定剂与死亡或OHT之间的关联仍然存在。= 0.003）。

结论： TTR稳定剂与TTR心脏淀粉样变性病的死亡和OHT降低有关。这些结果需要通过正在进行的随机临床试验来证实。