心肌水肿与淀粉样变的预后。

Myocardial Edema and Prognosis in Amyloidosis.

机构信息

National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom; Royal Free Hospital, London, United Kingdom.

National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom.

出版信息

J Am Coll Cardiol. 2018 Jun 26;71(25):2919-2931. doi: 10.1016/j.jacc.2018.03.536.

DOI:10.1016/j.jacc.2018.03.536

PMID:29929616

Abstract

BACKGROUND

Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTR amyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis.

OBJECTIVES

The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis.

METHODS

The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTR amyloidosis, 12 with suspected cardiac ATTR amyloidosis (grade 1 on Tc-3,3-diphosphono-1,2-propanodicarboxylic acid), 11 asymptomatic individuals with amyloidogenic TTR gene mutations, and 30 healthy volunteers. All subjects underwent cardiovascular magnetic resonance with T1 and T2 mapping and 16 underwent endomyocardial biopsy.

RESULTS

Myocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated AL patients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTR amyloidosis 54.2 ± 4.1 ms; each p < 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTR amyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p < 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67).

CONCLUSIONS

Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.

摘要

背景

轻链（AL）和转甲状腺素（ATTR）淀粉样变性的预后受心脏受累的影响。尽管 ATTR 淀粉样变性的淀粉样物质浸润更多，但预后优于 AL 淀粉样变性，这表明 AL 淀粉样变性中存在其他损伤机制。

目的

本研究旨在评估淀粉样变性患者心肌水肿的存在及其预后意义。

方法

本研究纳入了 286 名患者：100 名系统性 AL 淀粉样变性患者，163 名心脏 ATTR 淀粉样变性患者，12 名疑似心脏 ATTR 淀粉样变性患者（Tc-3,3-二膦酸-1,2-丙二醇酸 1 级），11 名无症状的淀粉样蛋白 TTR 基因突变个体，和 30 名健康志愿者。所有受试者均接受心血管磁共振 T1 和 T2 映射检查，其中 16 名受试者接受了心内膜心肌活检。

结果

淀粉样变性患者的心肌 T2 升高，未经治疗的 AL 患者升高程度最高（未经治疗的 AL 淀粉样变性患者 56.6±5.1ms；经治疗的 AL 淀粉样变性患者 53.6±3.9ms；ATTR 淀粉样变性患者 54.2±4.1ms；与对照组相比，各有 p<0.01：48.9±2.0ms）。与 AL 淀粉样变性相比，ATTR 淀粉样变性的左心室（LV）质量和细胞外容积分数更高，而 LV 射血分数更低（p<0.001）。活检样本中存在水肿的组织学证据，心肌受累范围为 5%至 40%（5%至 40%）。使用 Cox 回归模型，心肌 T2 可预测 AL 淀粉样变性患者的死亡（风险比：1.48；95%置信区间：1.20 至 1.82），并且在调整细胞外容积分数和 N 末端 B 型利钠肽前体后仍然具有统计学意义（风险比：1.32；95%置信区间：1.05 至 1.67）。