[Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases].

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.目的： 探讨心脏淀粉样变性不同类型的组织学特点及临床表现，以提高对该病的诊断水平。 方法： 收集四川大学华西医院2018年1月至2021年12月通过心内膜心肌活检，经刚果红染色及电镜观察证实的心脏淀粉样变性病例48例，采用免疫荧光、免疫组织化学染色检测免疫球蛋白轻链κ、λ及转甲状腺素蛋白的表达，总结其病理形态学特点及临床表现并复习相关文献。 结果： 48例患者年龄42~79岁（中位年龄56岁），≥50岁患者占81.3%（39/48）。男女比例1.1∶1.0。心肌活检确诊47例，活检阳性率97.9%，其检出率明显高于腹壁脂肪检出比例（7/17）。刚果红阳性率97.9%（47/48），电镜阳性率93.5%（43/46）。病理分型示轻链型32例（68.1%），其中轻链λ型31例，轻链κ型1例；转甲状腺素蛋白型（ATTR-CA）9例（19.1%）；未分型6例（12.8%）。不同病理分型的淀粉样物质沉积模式差异无统计学意义（P>0.05）。临床数据显示，ATTR-CA患者更少出现2个及以上器官或组织的累及，氨基末端B型利钠肽前体（NT-proBNP）明显低于其他两型患者（P<0.05），左心室每博输出量和右心室射血分数好于其他两型患者（P<0.05）。45例获得随访资料，总体平均生存时间为（15.6±2.0）个月。单因素生存分析发现，ATTR-CA患者预后较好，而心功能分级越高、NT-proBNP>6 000 ng/L、肌钙蛋白T>70 ng/L的心脏淀粉样变性患者预后差。多因素生存分析发现，NT-proBNP和心功能分级是心脏淀粉样变性患者的独立预后因素。 结论： 轻链λ型是本组心脏淀粉样变性最常见的病理类型；结合刚果红染色和电镜检查可显著提高心脏淀粉样变性确诊率；各病理类型的临床表现及预后不同。免疫染色是病理分型简单且有效的方法，但仍有少数病例不能分型，必要时可行质谱分析。.