Beltrami Matteo, Galluzzo Alessandro, Brocci Riccardo Tappa, Paoletti Perini Alessandro, Pieragnoli Paolo, Garofalo Manuel, Halasz Geza, Milli Massimo, Barilli Maria, Palazzuoli Alberto
Cardiology Unit, San Giovanni di Dio Hospital, Azienda USL Toscana Centro, Florence, Italy.
Cardiology Unit, Santa Croce Hospital, Moncalieri, Italy.
Front Cardiovasc Med. 2023 Jun 12;10:1180960. doi: 10.3389/fcvm.2023.1180960. eCollection 2023.
Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome. Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT.
Consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years.
Among the 86 patients enrolled, 44% experienced the primary outcome. In this group, the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, < 0.001, HR 8.33 (1.88-33.33), = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, < 0.001, HR 333 (250-1,000), = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood. Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08-1.22), < 0.001; HR: 0.84 (0.74-0.91), = 0.04; HR: 1.26 (1.10-1.43), ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome.
In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long-term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.
心脏再同步治疗（CRT）是射血分数降低的心力衰竭（HFrEF）特定患者的既定治疗方法。有人提出，心肌纤维化和炎症可能影响CRT“反应”和预后。我们的研究调查了有CRT指征的HFrEF患者心脏生物标志物的长期预后意义。
对连续转诊接受CRT植入的患者进行回顾性评估。在基线和随访1年后测量可溶性肿瘤抑制因子2（sST2）、半乳糖凝集素-3（Gal-3）、B型利钠肽N末端（NT-proBNP）和估计肾小球滤过率（eGFR）。进行多变量分析以评估它们与平均随访9±2年时心血管死亡和心力衰竭住院的主要复合结局的相关性。
在纳入的86例患者中，44%发生了主要结局。在这组患者中，NT-proBNP、Gal-3和sST2的平均基线值显著高于无心血管事件的患者。在多变量分析中，基线Gal-3[临界值：16.6 ng/ml，AUC：0.91，P<0.001，HR 8.33（1.88-33.33），P=0.005]和sST2[临界值：35.6 ng/ml，AUC：0.91，P<0.001，HR 333（250-1,000），P=0.003]在预测模型中与复合结局显著相关且可能性高。在1年随访时评估的参数中，sST2、eGFR以及Gal-3水平从基线到1年的变化与主要结局密切相关[HR分别为1.15（1.08-1.22），P<0.001；HR：0.84（0.74-0.91），P=0.04；HR：1.26（1.10-1.43），P≤0.001]。相反，CRT反应的超声心动图定义与任何结局均无相关性。
在接受CRT的HFrEF患者中，sST2、Gal-3和肾功能与长期随访时心血管死亡和心力衰竭住院的联合终点相关，而超声心动图CRT反应似乎不影响患者的结局。
