Department of Medicine, Division of Cardiology, Columbia University Medical Center/New York-Presbyterian Hospital.
Circ Heart Fail. 2018 Apr;11(4):e004769. doi: 10.1161/CIRCHEARTFAILURE.117.004769.
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.
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; <0.0001). Subjects treated with stabilizers were more likely to be of White race (93% versus 55%; <0.001), classified as New York Heart Association classes I and II (79% versus 38%; =0.002), less likely to have a mutation (10% versus 36%; =0.010), have lower troponin I (median 0.06 versus 0.12 ng/mL; =0.002), and higher left ventricular ejection fraction (49% versus 40%; =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 <0.05 (hazard ratio, 0.37; 95% confidence interval, 0.19-0.75; =0.003).
TTR stabilizers are associated with decreased death and OHT in TTR cardiac amyloidosis. These results need to be confirmed by ongoing randomized clinical trials.
转甲状腺素蛋白（TTR）心脏淀粉样变性是由 TTR 单体解离引起的，这些单体错误地组装成淀粉样纤维。TTR 稳定剂作用于二聚体-二聚体界面，以防止解离。我们研究了接受 TTR 心脏淀粉样变性稳定剂治疗的患者与未接受稳定剂治疗的患者之间的生存率差异。
对单一中心就诊的 TTR 心脏淀粉样变性患者进行回顾性研究。比较了接受和未接受稳定剂治疗的患者的基线特征。Cox 比例风险模型评估了死亡或原位心脏移植（OHT）复合终点的单变量预测因素。多变量 Cox 比例风险评估在控制重要单变量预测因素后，稳定剂治疗是否与死亡率或 OHT 降低独立相关。共纳入 120 例患者（平均年龄 75±8 岁，88%为男性）：29 例接受稳定剂治疗，91 例未接受稳定剂治疗。稳定剂治疗与死亡或 OHT 的复合终点风险降低相关（风险比 0.32；95%置信区间 0.18-0.58；<0.0001）。接受稳定剂治疗的患者更有可能为白人（93%比 55%；<0.001），纽约心脏协会（NYHA）心功能分级 I 和 II 级（79%比 38%；=0.002），发生突变的可能性较低（10%比 36%；=0.010），肌钙蛋白 I 水平较低（中位数 0.06 比 0.12 ng/mL；=0.002），左心室射血分数较高（49%比 40%；=0.011），提示疾病处于较早阶段。在多变量 Cox 分析中，当调整所有非共线性<0.05 的单变量预测因素时，稳定剂与死亡或 OHT 之间的关联仍然存在（风险比 0.37；95%置信区间 0.19-0.75；=0.003）。
TTR 稳定剂与 TTR 心脏淀粉样变性患者的死亡率和 OHT 降低相关。这些结果需要正在进行的随机临床试验来证实。
