Aims Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, it is not yet known whether tafamidis affects cardiac amyloid deposition and structural changes in the myocardium. We aimed to determine disease-modifying effects on myocardial amyloid progression and to identify imaging parameters that could be applied for specific therapy monitoring. Methods and results ATTR-CM patients underwent serial cardiac magnetic resonance (CMR) imaging using T1 mapping techniques to derive extracellular volume (ECV). Patients receiving tafamidis 61 mg (n = 35) or 20 mg (n = 15) once daily showed stable measurements at follow-up (FU) {61 mg: 9.0 [interquartile range (IQR) 7.0–11.0] months, 20 mg: 11.0 (IQR 8.0–18.0) months} in left ventricular (LV) ejection fraction (LVEF; 61 mg: 47.6% vs. 47.5%, P = 0.935; 20 mg: 52.4% vs. 52.1%, P = 0.930), LV mass index (LVMI; 61 mg: 110.2 vs. 106.2 g/m2, P = 0.304; 20 mg: 114.5 vs. 115.4 g/m2, P = 0.900), and ECV (61 mg: 47.5% vs. 47.7%, P = 0.861; 20 mg: 56.7% vs. 57.5%, P = 0.759), whereas treatment-naïve ATTR-CM patients (n = 19) had clear signs of disease progression at the end of the observation period [12.0 (IQR 10.0–21.0) months; LVEF: 53.3% vs. 45.7%, P = 0.031; LVMI: 98.9 vs. 106.9 g/m2, P = 0.027; ECV: 49.3% vs. 54.6%, P = 0.023]. Between-group comparison at FU revealed positive effects in tafamidis 61 mg-treated compared to treatment-naïve patients (LVEF: P = 0.035, LVMI: P = 0.036, ECV: P = 0.030), while those treated with 20 mg showed no difference in the above LV measurements when compared with treatment-naïve (P = 0.120, P = 0.287, P = 0.158). However, both treatment groups showed clinically beneficial effects compared to the natural course [61 mg, 6-min walk distance (6-MWD): P = 0.005, N-terminal prohormone of brain natriuretic peptide (NT-proBNP): P = 0.002; 20 mg, 6-MWD: P = 0.023, NT-proBNP: P = 0.003]. Conclusion Tafamidis delays myocardial amyloid progression in ATTR-CM patients, resulting in structural, functional, and clinical benefits compared to the natural course. Serial CMR including measurement of ECV may be appropriate for disease-specific therapy monitoring.

中文翻译：

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Tafamidis 治疗延迟转甲状腺素蛋白淀粉样蛋白心肌病患者左心室的结构和功能变化

目标 Tafamidis 可改善转甲状腺素蛋白淀粉样蛋白心肌病 (ATTR-CM) 患者的预后。然而，目前尚不清楚 tafamidis 是否会影响心肌淀粉样蛋白沉积和心肌结构变化。我们旨在确定对心肌淀粉样蛋白进展的疾病缓解作用，并确定可用于特定治疗监测的成像参数。方法和结果 ATTR-CM 患者使用 T1 映射技术进行连续心脏磁共振 (CMR) 成像以获得细胞外体积 (ECV)。每天一次接受 tafamidis 61 mg (n = 35) 或 20 mg (n = 15) 的患者在随访 (FU) {61 mg: 9.0 [四分位间距 (IQR) 7.0–11.0] 个月时显示稳定测量值, 20 mg: 11.0 (IQR 8.0–18.0) 个月} 左心室 (LV) 射血分数 (LVEF; 61 mg: 47.6% vs. 47.5%, P = 0.935; 20 mg: 52。4% 对 52.1%，P = 0.930），LV 质量指数（LVMI；61 毫克：110.2 对 106.2 克/平方米，P = 0.304；20 毫克：114.5 对 115.4 克/平方米，P = 0.900）和ECV（61 mg：47.5% vs. 47.7%，P = 0.861；20 mg：56.7% vs. 57.5%，P = 0.759），而未经治疗的 ATTR-CM 患者（n = 19）有明显的疾病进展迹象在观察期结束时 [12.0 (IQR 10.0–21.0) 个月；LVEF：53.3% 对 45.7%，P = 0.031；LVMI：98.9 对 106.9 g/m2，P = 0.027；ECV：49.3% 对 54.6%，P = 0.023]。FU 组间比较显示，与未接受过治疗的患者相比，接受 61 mg tafamidis 治疗的患者具有积极作用（LVEF：P = 0.035，LVMI：P = 0.036，ECV：P = 0.030），而接受 20 mg 治疗的患者没有差异在上述 LV 测量中，与初治相比（P = 0.120，P = 0.287，P = 0.158）。然而，与自然疗程相比，两个治疗组均显示出临床有益效果 [61 mg，6 分钟步行距离 (6-MWD)：P = 0.005，脑利钠肽 N 端激素原 (NT-proBNP)：P = 0.002；20 毫克，6-MWD：P = 0.023，NT-proBNP：P = 0.003]。结论 Tafamidis 可延缓 ATTR-CM 患者的心肌淀粉样蛋白进展，与自然病程相比，可带来结构、功能和临床益处。包括 ECV 测量在内的系列 CMR 可能适用于疾病特异性治疗监测。和与自然过程相比的临床益处。包括 ECV 测量在内的系列 CMR 可能适用于疾病特异性治疗监测。和与自然过程相比的临床益处。包括 ECV 测量在内的系列 CMR 可能适用于疾病特异性治疗监测。