From the Charité-Universitätsmedizin Berlin, corporate member of Freie Universitaät Berlin, Humboldt-Universitaät zu Berlin, and Berlin Institute of Health, Institute of Pharmacology, Center for Cardiovascular Research, Berlin, Germany (N.B., A.F.-L., S.B., J.G., Arne Thiele, U.K.).
DZHK (German Centre for Cardiovascular Research), Partner site Berlin, Germany (N.B., A.F.-L., S.B., J.G., Arne Thiele, L.E., Arata Tabuchi, W.M.K., B.P., U.K.).
Hypertension. 2019 Aug;74(2):295-304. doi: 10.1161/HYPERTENSIONAHA.119.12956. Epub 2019 Jul 10.
Subendocardial damage is among the first cardiac manifestations of hypertension and is already present in asymptomatic disease states. Accordingly, markers of subendocardial impairment may facilitate early detection of cardiac damages and risk stratification under these conditions. This study aimed to investigate the impact of subendocardial damage on myocardial microstructure and function to elucidate early pathophysiologic processes and to identify corresponding diagnostic measures. Mice (n=38) were injected with isoproterenol to induce isolated subendocardial scarring or saline as corresponding control. Cardiac function and myocardial deformation were determined by high-frequency echocardiography. The cardiac stress response was assessed in a graded exercise test and during dobutamine stress echocardiography. Myocardial microstructure was studied ex vivo by 7 T diffusion tensor magnetic resonance imaging at a spatial resolution of 100×100×100 µm . Results were correlated with histology and biomarker expression. Subendocardial fibrosis was accompanied by diastolic dysfunction, impaired longitudinal deformation (global peak longitudinal strain [LS]: -12.5±0.5% versus -15.6±0.5%; P<0.001) and elevated biomarker expression (ANP [atrial natriuretic peptide], Galectin-3, and ST2). Systolic function and cardiac stress response remained preserved. Diffusion tensor magnetic resonance imaging revealed a left-shift in helix angle towards lower values in isoproterenol-treated animals, which was mainly determined by subepicardial myofibers (mean helix angle: 2.2±0.8° versus 5.9±1.0°; P<0.01). Longitudinal strain and subepicardial helix angle were highly predictive for subendocardial fibrosis (sensitivity, 82%-92% and specificity, 89%-90%). The results indicate that circumscribed subendocardial damage alone can cause several hallmarks observed in cardiovascular high-risk patients. Microstructural remodeling under these conditions involves also remote regions, and corresponding changes in longitudinal strain and helix angle might serve as diagnostic markers.
心内膜下损伤是高血压的最早心脏表现之一，即使在无症状疾病状态下也已存在。因此，心内膜下损伤的标志物可能有助于在这些情况下更早地发现心脏损伤和进行风险分层。本研究旨在探讨心内膜下损伤对心肌微观结构和功能的影响，以阐明早期病理生理过程，并确定相应的诊断措施。研究人员给小鼠注射异丙肾上腺素诱导孤立的心内膜下瘢痕形成，或注射生理盐水作为相应对照。通过高频超声心动图测定心功能和心肌变形。通过分级运动试验和多巴酚丁胺超声心动图评估心脏应激反应。通过 7T 扩散张量磁共振成像（分辨率为 100×100×100μm）在体研究心肌微观结构。将结果与组织学和生物标志物表达相关联。心内膜下纤维化伴有舒张功能障碍、纵向应变受损（整体纵向应变峰值 [LS]：-12.5±0.5%对-15.6±0.5%；P<0.001）和生物标志物表达升高（心房利钠肽[ANP]、半乳糖凝集素-3 和 ST2）。收缩功能和心脏应激反应保持不变。扩散张量磁共振成像显示异丙肾上腺素处理的动物的螺旋角向左移向较低值，这主要由心外膜心肌纤维决定（平均螺旋角：2.2±0.8°对 5.9±1.0°；P<0.01）。纵向应变和心外膜螺旋角对心内膜下纤维化具有高度预测性（敏感性为 82%-92%，特异性为 89%-90%）。结果表明，单独的局限性心内膜下损伤可引起心血管高危患者中观察到的多种特征。在这些情况下，微观结构重塑还涉及到远程区域，纵向应变和螺旋角的相应变化可能作为诊断标志物。
