Katznelson Ethan, Jerosch-Herold Michael, Cuddy Sarah A M, Clerc Olivier F, Benz Dominik C, Taylor Alexandra, Rao Shivani, Kijewski Marie Foley, Liao Ronglih, Landau Heather, Yee Andrew J, Ruberg Frederick L, Di Carli Marcelo F, Falk Rodney H, Kwong Raymond Y, Dorbala Sharmila
Department of Cardiology, Weill Cornell Medical Center, New York, NY, United States.
CV Imaging Program, Cardiovascular Division and Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States.
Front Cardiovasc Med. 2024 May 30;11:1371810. doi: 10.3389/fcvm.2024.1371810. eCollection 2024.
Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood.
This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis.
Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass.
Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE ( = 0.42; < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy ( = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile ( < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden.
In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.
心脏收缩功能障碍是轻链（AL）心肌病（一种原发性间质疾病）的不良预后标志物；然而，其发病机制尚不清楚。
本研究旨在分析细胞外容积（ECV）扩大（淀粉样蛋白负荷的替代标志物）对AL淀粉样变性患者心肌血流（MBF）、心肌工作效率（MWE）和左心室（LV）收缩功能障碍的影响。
前瞻性纳入经活检证实的AL淀粉样变性患者（2016年4月至2021年6月；Clinicaltrials.gov标识符NCT02641145），并接受心脏磁共振成像（MRI）检查，通过灌注成像量化静息MBF，通过电影MRI量化左心室射血分数（LVEF），通过对比剂前后T1映射量化ECV。MWE通过每搏量和平均动脉压计算得出的心脏外部功，并将其归一化为左心室心肌质量来估计。
92例AL淀粉样变性患者（62±8岁，52例男性）的静息MBF平均为0.87±0.21ml/min/g，且与MWE相关（r=0.42；P<0.001）。成功治疗AL淀粉样变性后血液学持续缓解的患者（n=21）的静息MBF同样较低，与近期诊断的AL淀粉样变性患者相同。MBF和MWE均随ECV三分位数降低（线性趋势P<0.01）。ECV与MWE的关联包括通过ECV评估的不良间质重塑对MWE的直接影响（占总效应的84%；P<0.001）和由MBF介导的间接影响（占总效应的16%；P<0.001）。淀粉样蛋白负荷较高的患者静息MBF存在显著的心底到心尖梯度。
在AL淀粉样变性中，随着心脏淀粉样蛋白负荷和ECV扩大增加，MBF和MWE均降低。ECV扩大和心肌淀粉样蛋白负荷引起的结构和血管变化似乎都导致MWE降低。
