Musigk Nicolas, Suwalski Phillip, Müller Maximilian, Violano Michele, Klingel Karin, Weiner January, Beule Dieter, Landmesser Ulf, Heidecker Bettina
Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Hindenburgdamm 30, 12203 Berlin, Germany.
Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tübingen, 72076 Tübingen, Germany.
Biomedicines. 2025 Sep 12;13(9):2254. doi: 10.3390/biomedicines13092254.
Myocardial inflammation in cardiac amyloidosis is associated with poor clinical outcomes. This study aimed to (a) investigate the relationship between peripheral blood cytokine levels and the presence of inflammatory cells within the myocardium, and to (b) evaluate the potential of cytokines as predictors of major adverse cardiovascular events (MACE) in transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis. Peripheral blood samples were collected from 50 patients with cardiac ATTR or AL amyloidosis between 2018 and 2023 at baseline and every three months during follow-up visits. Cytokine analysis was performed using Olink's Proximity Extension Assay. For MACE prediction analysis, only patients with MACE occurring within ±14 days of a study visit were included ( = 16). Associations were evaluated using linear models. No significant associations were identified between the EMB-confirmed myocardial presence of inflammatory cells and cytokine levels. There was a trend of weak-to-moderate associations between serial blood cytokine levels and MACE, albeit this was non-significant after adjustment for multiple testing (FDR): r = 0.28 for PON3 ( = 0.00075, FDR = 0.28), SIGLEC1 ( = 0.00077, FDR = 0.28), and IL-6 ( = 0.00086, FDR = 0.31). Peripheral blood cytokine levels were not reliable biomarkers for the myocardial presence of inflammatory cells. PON3, SIGLEC1, and IL-6 demonstrated a statistically non-significant trend of a weak-to-moderate association with MACE in cardiac amyloidosis. Since we recently demonstrated that amyloidosis with an inflammatory component is associated with poor outcomes, these additional findings underscore the need for alternative approaches to identify and manage inflammation in this patient population.
心脏淀粉样变性中的心肌炎症与不良临床结局相关。本研究旨在：(a) 探究外周血细胞因子水平与心肌内炎症细胞存在之间的关系，以及 (b) 评估细胞因子作为转甲状腺素蛋白 (ATTR) 和免疫球蛋白轻链 (AL) 心脏淀粉样变性中主要不良心血管事件 (MACE) 预测指标的潜力。在2018年至2023年期间，从50例心脏ATTR或AL淀粉样变性患者中采集外周血样本，在基线时以及随访期间每三个月采集一次。使用欧林克的邻近延伸分析进行细胞因子分析。对于MACE预测分析，仅纳入在研究访视±14天内发生MACE的患者（n = 16）。使用线性模型评估相关性。心内膜活检确认的心肌炎症细胞存在与细胞因子水平之间未发现显著相关性。系列血细胞因子水平与MACE之间存在弱至中度相关性趋势，尽管在多重检验校正（FDR）后不显著：对氧磷酶3（PON3）的r = 0.28（P = 0.00075，FDR = .28）、唾液酸结合免疫球蛋白样凝集素1（SIGLEC1）的r = 0.00077（P = 0.00077，FDR = 0.28）和白细胞介素-6（IL-6）的r = 0.00086（P = 0.00086，FDR = 0.31）。外周血细胞因子水平不是心肌炎症细胞存在的可靠生物标志物。PON（3）、SIGLEC1和IL-6在心脏淀粉样变性中与MACE呈弱至中度相关性，在统计学上无显著趋势。由于我们最近证明具有炎症成分的淀粉样变性与不良结局相关，这些额外的发现强调了需要采用替代方法来识别和管理该患者群体中的炎症。
