TTR (Transthyretin) Stabilizers Are Associated With Improved Survival in Patients With TTR Cardiac Amyloidosis.
TTR (Transthyretin) Stabilizers Are Associated With Improved Survival in Patients With TTR Cardiac Amyloidosis.
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DOI：
10.1161/circheartfailure.117.004769
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
Maurer MS
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文献类型：
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作者：
Rosenblum H;Castano A;Alvarez J;Goldsmith J;Helmke S;Maurer MS
甲状腺素运载蛋白心脏淀粉样变性（TTR-CA）是由甲状腺素运载蛋白（TTR）解离成单体，这些单体错误组装成淀粉样纤维引起的。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TTR-CA患者使用稳定剂治疗与未使用稳定剂治疗的生存率差异。对在单中心就诊的TTR-CA患者进行了一项回顾性研究。比较了接受稳定剂治疗和未接受稳定剂治疗的患者的基线特征。考克斯比例风险模型评估死亡或原位心脏移植（OHT）复合结局的单变量预测因子。多变量考克斯比例风险评估在控制显著单变量预测因素后，稳定剂治疗是否与死亡或OHT改善独立相关。纳入了120例患者（平均年龄75±8岁，88%为男性）：29例患者接受稳定剂治疗，91例患者未接受稳定剂治疗。使用稳定剂与死亡或OHT的联合终点风险较低相关（HR 0.32，95% CI 0.18-0.58，p<0.0001）。接受稳定剂治疗的受试者更可能是白色人种（93% vs. 55%，p<0.001），分类为NYHA I-II级（79%与38%，p=0.002），发生突变的可能性较小（10% vs. 36%，p=0.010），肌钙蛋白I较低（中位数0.06 vs. 0.12 ng/mL，P=0.002），LVEF较高（49% vs. 40%，p=0.011），表明疾病处于早期阶段。在多变量考克斯分析中，当调整所有非共线单变量预测因素时，稳定剂与死亡或OHT之间的相关性持续存在，p<0.05（HR 0.37，95% CI 0.19-0.75，p=0.003）。TTR稳定剂与TTR-CA中死亡和OHT减少相关。这些结果需要通过正在进行的随机临床试验来证实。
Transthyretin cardiac amyloidosis (TTR-CA) is caused by dissociation of transthyretin (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-CA on stabilizer medications compared to those not on stabilizers. A retrospective study of patients with TTR-CA 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. 120 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 endpoint of death or OHT (HR 0.32, 95% CI 0.18-0.58, p<0.0001). Subjects treated with stabilizers were more likely to be of White race (93% vs. 55%, p<0.001), classified as NYHA Class I-II (79% vs. 38%, p=0.002), less likely to have a mutation (10% vs. 36%, p=0.010), have lower troponin I (median 0.06 vs. 0.12 ng/mL, P=0.002), and higher LVEF (49% vs. 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 non-collinear univariate predictors with p<0.05 (HR 0.37, 95% CI 0.19-0.75, p=0.003). TTR stabilizers are associated with decreased death and OHT in TTR-CA. These results need to be confirmed by ongoing randomized clinical trials.