Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands.
Clinical Genetics (J.A.J.V., K.W.J.D., P.W., H.G.B.), Maastricht University Medical Center, the Netherlands.
Circ Arrhythm Electrophysiol. 2020 Nov;13(11):e008727. doi: 10.1161/CIRCEP.120.008727. Epub 2020 Sep 30.
Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies.
Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as >14 infiltrating cells/mm. Echocardiographic left ventricular end-systolic volume reduction ≥15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders.
Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12-0.76]; =0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test <0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular, , and were significantly higher expressed in the hearts of nonresponders.
Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM.
心脏再同步治疗（CRT）是扩张型心肌病（DCM）伴传导障碍患者的一种既定治疗方法。然而，仍有三分之一的 DCM 患者对 CRT 无反应。本研究旨在通过心肌活检描绘 DCM 患者对 CRT 无反应的潜在心脏病理生理过程。
在 Maastricht 和 Innsbruck 注册中心的 DCM 患者中，99 例患者在 CRT 植入前接受了心肌活检，对纤维化和炎症进行组织学量化，其中炎症定义为>14 个浸润细胞/mm。6 个月后超声心动图左心室收缩末期容积减少≥15%定义为 CRT 反应。从反应者和无反应者的代表性亚组的心脏活检中分离 RNA。
67 例患者（68%）对 CRT 有反应，而 32 例（32%）无反应。植入前的心脏炎症与 CRT 反应呈负相关（25%的反应者，47%的无反应者；比值比 0.3 [0.12-0.76]；=0.01）。心肌活检纤维化与 CRT 反应无关。心脏炎症改善了预测的稳健性，超越了 CRT 反应的已知临床预测因子（似然比检验<0.001）。心肌活检的心脏转录组分析显示，与反应者相比，无反应者心脏中存在强烈的促炎和促纤维化特征。特别是 、 和 在无反应者的心脏中表达显著升高。
DCM 患者对 CRT 反应不良与心脏炎症以及高表达的促炎和促纤维化基因转录组特征有关。
