Department of Medicine, Cardiology Goethe University Hospital Frankfurt Germany.
German Centre for Cardiovascular ResearchPartner Site Frankfurt Rhine-Main Berlin Germany.
J Am Heart Assoc. 2022 Mar 15;11(6):e022792. doi: 10.1161/JAHA.121.022792. Epub 2022 Mar 1.
Background Musclin is an activity-stimulated and cardioprotective myokine that attenuates pathological cardiac remodeling. Musclin deficiency, in turn, results in reduced physical endurance. The aim of this study was to assess the prognostic value of circulating musclin as a novel, putative biomarker to identify patients undergoing transcatheter aortic valve implantation (TAVI) who are at a higher risk of death. Methods and Results In this study, we measured systemic musclin levels in 368 patients undergoing TAVI who were at low to intermediate clinical risk (median EuroSCORE [European System for Cardiac Operative Risk Evaluation] II: 3.5; quartile 1-quartile, 2.2%-5.3%), whereby 209 (56.8%) patients were at low and 159 (43.2%) were at intermediate risk. Median preprocedural musclin levels were 2.7 ng/mL (quartile 1-quartile 3, 1.5-4.6 ng/mL). Musclin levels were dichotomized in low (<2.862 ng/mL, n=199 [54.1%]) or high (≥ 2.862 ng/mL, n=169 [45.9%]) groups using cutoff values determined by classification and regression tree analysis. The primary end point was 1-year overall survival. Patients with low circulating musclin levels exhibited a significantly higher prevalence of frailty, low albumin values, hypertension, and history of stroke as well as higher N-terminal pro-B-type natriuretic peptide. Low musclin levels significantly predicted risk of death in univariable (hazard ratio, 1.81; 95% CI, 1.00-3.53 [=0.049]) and multivariable (adjusted hazard ratio, 2.45; 95% CI, 1.06-5.69 [=0.037]) Cox regression analyses. Additionally, low musclin levels in combination with conventional EuroSCORE II suggested improved risk stratification in patients undergoing TAVI who were at low to intermediate clinical risk into subgroups with reduced 1-year survival rates by log-rank test ( for trend=0.003). Conclusions Circulating musclin is an independent predictor of 1-year overall survival in patients undergoing TAVI. Combined with EuroSCORE II, circulating musclin might help to improve prediction of mortality in patients undergoing TAVI who are at low to intermediate clinical risk.
背景肌联蛋白是一种活性刺激和心脏保护的肌因子，可减轻病理性心脏重构。反过来，肌联蛋白缺乏会导致身体耐力降低。本研究旨在评估循环肌联蛋白作为一种新型潜在生物标志物的预后价值，以识别接受经导管主动脉瓣植入术（TAVI）的患者，这些患者死亡风险更高。
方法和结果在这项研究中，我们测量了 368 例低至中临床风险（中位欧洲心脏手术风险评估系统 II[EuroSCORE II]：3.5；四分位 1-四分位 3，2.2%-5.3%）接受 TAVI 的患者的系统肌联蛋白水平，其中 209 例（56.8%）为低风险，159 例（43.2%）为中风险。术前中位肌联蛋白水平为 2.7ng/mL（四分位 1-四分位 3，1.5-4.6ng/mL）。使用分类回归树分析确定的截断值将肌联蛋白水平分为低（<2.862ng/mL，n=199[54.1%]）或高（≥2.862ng/mL，n=169[45.9%]）组。主要终点是 1 年总生存率。循环肌联蛋白水平低的患者表现出更高的虚弱、低白蛋白值、高血压和中风病史以及更高的 N 末端 pro-B 型利钠肽。单变量（危险比，1.81；95%CI，1.00-3.53[=0.049]）和多变量（调整后的危险比，2.45；95%CI，1.06-5.69[=0.037]）Cox 回归分析显示，低肌联蛋白水平显著预测死亡风险。此外，低肌联蛋白水平与传统的 EuroSCORE II 联合使用，通过对数秩检验（ for trend=0.003）提示在低至中临床风险的接受 TAVI 的患者中进行风险分层，将 1 年生存率降低的亚组（趋势=0.003）。
结论循环肌联蛋白是接受 TAVI 的患者 1 年总生存率的独立预测因子。与 EuroSCORE II 联合使用，循环肌联蛋白可能有助于改善低至中临床风险接受 TAVI 的患者的死亡率预测。
