Department of Cardiology, Heart Center, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
Am J Physiol Heart Circ Physiol. 2024 Oct 1;327(4):H1086-H1097. doi: 10.1152/ajpheart.00335.2024. Epub 2024 Aug 30.
Coronary vasomotor dysfunction, an important underlying cause of angina and nonobstructive coronary arteries (ANOCA), encompassing coronary vasospasm, coronary endothelial dysfunction, and/or coronary microvascular dysfunction, is clinically assessed by invasive coronary function testing (ICFT). As ICFT imposes a high burden on patients and carries risks, developing noninvasive alternatives is important. We evaluated whether coronary vasomotor dysfunction is a component of systemic microvascular endothelial and smooth muscle dysfunction and can be detected using laser speckle contrast analysis (LASCA). Forty-three consecutive patients with ANOCA underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA in the forearm, combined with vasodilators acetylcholine, sodium nitroprusside, and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Of the 43 included patients with ANOCA (79% women, 59 ± 9 yr old), 38 patients had coronary vasomotor dysfunction, including 28 with coronary vasospasm, 26 with coronary endothelial dysfunction, and 18 with coronary microvascular dysfunction, with overlapping endotypes. Patients with and without coronary vasomotor dysfunction had similar peripheral flow responses to acetylcholine, insulin, and RHI. In contrast, coronary vasomotor dysfunction was associated with lower peripheral flow responses to sodium nitroprusside ( < 0.001). An absolute flow response to sodium nitroprusside of 83.95 APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve, 0.883; = 0.006). In conclusion, this study provides evidence of systemic vascular smooth muscle dysfunction in patients with ANOCA with coronary vasomotor dysfunction and the diagnostic value of peripheral microvascular function testing as a noninvasive tool for detecting coronary vasomotor dysfunction. This study provides proof of concept that assessment of the peripheral vasculature, particularly vascular smooth muscle cells measured using the LASCA technology holds potential as a noninvasive tool for detecting coronary vasomotor dysfunction. This finding highlights the potential of the LASCA technology in, for example, medication studies for coronary vasomotor dysfunction, especially when investigating whether medication improves vascular function, as repeated peripheral measurements are less invasive than invasive coronary function testing, the current gold standard.
冠状动脉血管运动功能障碍是心绞痛和非阻塞性冠状动脉(ANOCA)的一个重要潜在原因,包括冠状动脉痉挛、冠状动脉内皮功能障碍和/或冠状动脉微血管功能障碍,通过有创冠状动脉功能测试(ICFT)进行临床评估。由于 ICFT 给患者带来了很高的负担并存在风险,因此开发非侵入性替代方法很重要。我们评估了冠状动脉血管运动功能障碍是否是全身微血管内皮和平滑肌功能障碍的一个组成部分,以及是否可以使用激光散斑对比分析(LASCA)检测到。43 例连续 ANOCA 患者接受了 ICFT,包括冠状动脉内乙酰胆碱、腺苷和流量测量,以评估冠状动脉血管运动功能障碍。前臂采用 LASCA 评估皮肤微血管功能,同时使用乙酰胆碱、硝普钠和胰岛素作为血管扩张剂,并使用 EndoPAT 通过测量反应性充血指数(RHI)进行测量。43 例纳入的 ANOCA 患者(79%为女性,59±9 岁)中,38 例存在冠状动脉血管运动功能障碍,包括 28 例冠状动脉痉挛、26 例冠状动脉内皮功能障碍和 18 例冠状动脉微血管功能障碍,存在重叠的表型。有和没有冠状动脉血管运动功能障碍的患者对乙酰胆碱、胰岛素和 RHI 的外周血流反应相似。相比之下,冠状动脉血管运动功能障碍与硝普钠的外周血流反应较低有关(<0.001)。硝普钠的绝对血流反应为 83.95 APU 时,对冠状动脉血管运动功能障碍的敏感性为 86.1%,特异性为 80.0%(ROC 曲线下面积,0.883;=0.006)。总之,这项研究提供了证据表明,ANOCA 患者的冠状动脉血管运动功能障碍与全身血管平滑肌功能障碍有关,外周微血管功能测试作为一种非侵入性工具检测冠状动脉血管运动功能障碍具有诊断价值。这项研究提供了概念验证,即评估外周血管,特别是使用 LASCA 技术测量的血管平滑肌细胞,作为一种非侵入性工具检测冠状动脉血管运动功能障碍具有潜力。这一发现强调了 LASCA 技术的潜力,例如在冠状动脉血管运动功能障碍的药物研究中,特别是在研究药物是否改善血管功能时,因为重复的外周测量比有创冠状动脉功能测试侵入性更小,是当前的金标准。