Wu M, Zhang S Y, Lu Y, Tian Z, Zhang S Y
Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2025 Jul 24;53(7):776-783. doi: 10.3760/cma.j.cn112148-20250310-00176.
To explore the relationship between retinol-binding protein (RBP) levels and disease severity in patients with transthyretin cardiac amyloidosis (ATTR-CA), as well as its impact on therapeutic response to tafamidis. This retrospective study utilized data from the China National Rare Disease Registry System and included ATTR-CA patients treated with tafamidis between January 2018 and September 2022. Patients were stratified into two groups based on baseline RBP levels: the normal RBP group (≥36 mg/L) and the reduced RBP group (<36 mg/L). Baseline characteristics and clinical data after one year of treatment were collected and compared between the groups. Within the reduced RBP group, patients were further subclassified by changes in RBP levels after treatment (ΔRBP=post-treatment RBP-baseline RBP) into ΔRBP>0 and ΔRBP<0 subgroups. Worsening of global longitudinal strain (GLS) after treatment was defined as the primary outcome, logistic regression analysis was used to identify risk factors influencing therapeutic response to tafamidis in ATTR-CA patients. A total of 52 ATTR-CA patients were included (aged (58.5±12.0) years, 46 males (88%)). Among 39 patients who completed one-year tafamidis treatment, no statistically significant difference was observed in RBP levels post-treatment versus baseline ((27.0±14.3) mg/L vs. (25.9±15.4) mg/L, =0.261). Compared to the normal RBP group, the reduced RBP group had significantly higher estimated glomerular filtration rate-adjusted N-terminal pro-B-type natriuretic peptide levels (2 316.0 (1 161.5, 6 027.8) ng/L vs. 806.2 (349.5, 1 735.8) ng/L), higher left ventricular mass index ((164.4±46.5) g/m² vs. (123.9±31.8) g/m²), and lower left ventricular ejection fraction ((50.8±11.3)% vs. (58.8±6.2)%) (all <0.05). Among 31 patients in the reduced RBP group who completed one-year tafamidis treatment, 23 were classified as ΔRBP>0 and 8 as ΔRBP<0. The ΔRBP<0 group exhibited greater GLS worsening than the ΔRBP>0 group (0.7 (-0.1, 1.4)% vs. -0.4 (-1.4, 0.2)%, =0.027). Multivariate logistic regression analysis revealed that ΔRBP<0 was an independent risk factor for GLS worsening (=8.584, 1.186-62.150, =0.033) in ATTR-CA patients. ATTR-CA patients with reduced RBP levels exhibit more severe left ventricular structural and functional impairment compared to those with normal RBP levels. Decline in RBP during treatment (ΔRBP<0) is associated with poorer response to tafamidis treatment. Monitoring RBP dynamics may assist clinicians in assessing disease severity and therapeutic response in ATTR-CA patients.
探讨转甲状腺素蛋白心脏淀粉样变（ATTR-CA）患者视黄醇结合蛋白（RBP）水平与疾病严重程度之间的关系，以及其对tafamidis治疗反应的影响。这项回顾性研究利用了中国国家罕见病注册系统的数据，纳入了2018年1月至2022年9月期间接受tafamidis治疗的ATTR-CA患者。根据基线RBP水平将患者分为两组：正常RBP组（≥36 mg/L）和降低RBP组（<36 mg/L）。收集两组患者的基线特征和治疗一年后的临床数据并进行比较。在降低RBP组中，根据治疗后RBP水平的变化（ΔRBP = 治疗后RBP - 基线RBP）将患者进一步分为ΔRBP>0和ΔRBP<0亚组。将治疗后整体纵向应变（GLS）恶化定义为主要结局，采用逻辑回归分析确定影响ATTR-CA患者对tafamidis治疗反应的危险因素。共纳入52例ATTR-CA患者（年龄（58.5±12.0）岁，男性46例（88%））。在39例完成一年tafamidis治疗的患者中，治疗后RBP水平与基线相比无统计学显著差异（（27.0±14.3）mg/L对（25.9±15.4）mg/L，P = 0.261）。与正常RBP组相比，降低RBP组的估算肾小球滤过率校正N末端B型利钠肽原水平显著更高（2316.0（1161.5，6027.8）ng/L对806.2（349.5，1735.8）ng/L），左心室质量指数更高（（164.4±46.5）g/m²对（123.9±31.8）g/m²），左心室射血分数更低（（50.8±11.3）%对（58.8±6.2）%）（均P<0.05）。在降低RBP组中完成一年tafamidis治疗的31例患者中，23例分类为ΔRBP>0，8例分类为ΔRBP<0。ΔRBP<0组的GLS恶化程度高于ΔRBP>0组（0.7（-0.1，1.4）%对-0.4（-1.4，0.2）%，P = 0.027）。多因素逻辑回归分析显示，ΔRBP<0是ATTR-CA患者GLS恶化的独立危险因素（P = 8.584，95%CI 1.186 - 62.150，P = 0.033）。与RBP水平正常的ATTR-CA患者相比，RBP水平降低的患者表现出更严重的左心室结构和功能损害。治疗期间RBP下降（ΔRBP<0）与tafamidis治疗反应较差相关。监测RBP动态变化可能有助于临床医生评估ATTR-CA患者的疾病严重程度和治疗反应。
