晚期钠通道阻滞改善严重冠状动脉微血管功能障碍患者的心绞痛和心肌灌注：女性缺血综合征评估-冠状动脉血管功能障碍辅助研究。
Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study.
机构信息
Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, USA.
Barbara Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, USA.
出版信息
Int J Cardiol. 2019 Feb 1;276:8-13. doi: 10.1016/j.ijcard.2018.09.081. Epub 2018 Sep 26.
BACKGROUND
In a prior trial of late sodium channel inhibition (ranolazine) among symptomatic subjects without obstructive coronary artery disease (CAD) and limited myocardial perfusion reserve index (MPRI), we observed no improvement in angina or MPRI, overall. Here we describe the clinical characteristics and myocardial perfusion responses of a pre-defined subgroup who had coronary flow reserve (CFR) assessed invasively.
METHODS
Symptomatic patients without obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial of ranolazine vs. placebo were subjects of this prespecified substudy. Because we had previously observed that adverse outcomes and beneficial treatment responses occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs ≥2.5. Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and left-ventricular volume and MPRI were assessed by magnetic resonance imaging (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked to treatment and patient characteristics.
RESULTS
During qualifying coronary angiography, 81 patients (mean age 55 years, 98% women) had invasively determined CFR 2.69 ± 0.65 (mean ± SD; range 1.4-5.5); 43% (n = 35) had CFR <2.5. Demographic and symptomatic findings did not differ comparing CFR subgroups. Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p = 0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left-ventricular end-diastolic volume predicted a beneficial angina response.
CONCLUSIONS
Symptomatic patients with CFR <2.5 and no obstructive CAD had improved angina and myocardial perfusion with ranolazine, supporting the hypothesis that the late sodium channel is important in management of coronary microvascular dysfunction.
TRIAL REGISTRATION
clinicaltrials.gov Identifier NCT01342029.
背景
在一项针对无阻塞性冠状动脉疾病（CAD）和有限心肌灌注储备指数（MPRI）的症状性患者的晚期钠通道抑制（雷诺嗪）的先前试验中，我们观察到整体上心绞痛或 MPRI 没有改善。在这里，我们描述了一组预先定义的亚组的临床特征和心肌灌注反应，这些患者通过侵入性评估了冠状动脉血流储备（CFR）。
方法
在一项针对雷诺嗪与安慰剂的随机、双盲、交叉试验中，无症状性无阻塞性 CAD 和有限 MPRI 的患者是本预设亚研究的对象。由于我们之前观察到不良结局和有益的治疗反应发生在那些较低的 CFR 患者中，因此根据 CFR<2.5 与≥2.5 将患者分为亚组。使用西雅图心绞痛问卷和 SAQ-7 评估症状，通过磁共振成像（MRI）评估左心室容积和 MPRI。冠状动脉造影、CFR 和 MRI 数据由对治疗和患者特征进行盲法分析的核心实验室进行分析。
结果
在有资格进行冠状动脉造影期间，81 名患者（平均年龄 55 岁，98%为女性）的 CFR 为 2.69±0.65（平均值±标准差；范围 1.4-5.5）；43%（n=35）的 CFR<2.5。比较 CFR 亚组时，人口统计学和症状学发现没有差异。那些 CFR 较低的患者用雷诺嗪治疗时心绞痛（p=0.04）和中间段 MPRI（p=0.03）得到改善。在 CFR 较低的患者中，左心室舒张末期容积减少预测了有益的心绞痛反应。
结论
CFR<2.5 且无阻塞性 CAD 的症状性患者用雷诺嗪治疗时心绞痛和心肌灌注得到改善，支持晚期钠通道在管理冠状动脉微血管功能障碍中的重要性假设。
试验注册
clinicaltrials.gov 标识符 NCT01342029。
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