Wang Xuezhu, Shen Kaini, Zhang Yuke, Gao Yajuan, Liu Bowei, Guo Yubo, Ren Chao, Huang Zhenghai, Li Xiao, Chang Long, Ding Haiyan, Zhang Hui, Tian Zhuang, Hacker Marcus, Zhang Shuyang, Wang Yining, Li Jian, Li Xiang, Huo Li
Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
JACC Cardiovasc Imaging. 2025 Mar;18(3):323-336. doi: 10.1016/j.jcmg.2024.10.001. Epub 2025 Jan 8.
Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.
This prospective study aimed to delineate the molecular phenotypes of AL-cardiac amyloidosis (CA) by characterizing fibro-amyloid deposition using F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor (Ga-FAPI)-04 positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.
Patients with confirmed AL-CA underwent echocardiography and F-florbetapir and Ga-FAPI-04 PET/CT imaging. Cardiac amyloid burden was quantified as F-florbetapir cardiac amyloid volume and total cardiac amyloid. Meanwhile, cardiac fibroblast activation protein (FAP) was quantified as Ga-FAPI-04 cardiac fibroblast activation protein volume (CFV) and total cardiac fibroblast activation protein (TCF). PET/CT metrics were calculated in correlation to clinical and echocardiographic markers and their association with overall survival (OS) evaluated.
Among the 38 patients enrolled (median age: 58 years; 76.3% male), all patients exhibited amyloid deposition, and 86.8% (33 of 38) patients exhibited cardiac fibroblast activation. Cardiac amyloid burden was correlated with Mayo stage and several echocardiography metrics (P < 0.05). In addition, there was a correlation between CFV and N-terminal pro-B-type natriuretic peptide level (P < 0.05). Thirteen deaths occurred over a median follow-up of 24.8 months. Higher CFV and TCF were associated with shortened OS, particularly in Mayo stage III. In multivariable analysis, higher TCF was a primary determinant for shortened OS.
The study underscores that higher TCF on Ga-FAPI-04 PET/CT imaging might be a correlated factor of worse clinical outcome in newly diagnosed AL-CA, and this metric seems to be a molecular imaging tool complementary to F-florbetapir imaging. The combination might offer a holistic understanding of molecular attributes, assisting in clinical decision-making.
心脏受累于轻链（AL）淀粉样变性显著影响预后，需要及时诊断和细致的风险分层。
这项前瞻性研究旨在通过使用F-氟代硼吡和镓-68标记的成纤维细胞活化蛋白抑制剂（Ga-FAPI）-04正电子发射断层扫描（PET）/计算机断层扫描（CT）成像来表征纤维淀粉样沉积，从而描绘AL-心脏淀粉样变性（CA）的分子表型。作者还提出了一种用于预后的新型分子分层方法。
确诊为AL-CA的患者接受了超声心动图检查以及F-氟代硼吡和Ga-FAPI-04 PET/CT成像。心脏淀粉样蛋白负荷被量化为F-氟代硼吡心脏淀粉样蛋白体积和总心脏淀粉样蛋白。同时，心脏成纤维细胞活化蛋白（FAP）被量化为Ga-FAPI-04心脏成纤维细胞活化蛋白体积（CFV）和总心脏成纤维细胞活化蛋白（TCF）。计算PET/CT指标与临床和超声心动图标志物的相关性，并评估它们与总生存期（OS）的关联。
在纳入研究的38例患者中（中位年龄：58岁；76.3%为男性），所有患者均表现出淀粉样蛋白沉积，86.8%（38例中的33例）患者表现出心脏成纤维细胞活化。心脏淀粉样蛋白负荷与梅奥分期及多个超声心动图指标相关（P<0.05）。此外，CFV与N末端B型利钠肽原水平之间存在相关性（P<0.05）。在中位随访24.8个月期间发生了13例死亡。较高的CFV和TCF与较短的OS相关，尤其是在梅奥III期。在多变量分析中，较高的TCF是OS缩短的主要决定因素。
该研究强调，Ga-FAPI-04 PET/CT成像上较高的TCF可能是新诊断的AL-CA临床结局较差的相关因素，并且该指标似乎是一种与F-氟代硼吡成像互补的分子成像工具。两者结合可能有助于全面了解分子特征，辅助临床决策。
