A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.
A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.
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DOI：
10.1093/eurheartj/ehv647
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发表时间：
2016-05-14
影响因子：
39.3
通讯作者：
Pepine CJ
中科院分区：
文献类型：
--
作者：
Bairey Merz CN;Handberg EM;Shufelt CL;Mehta PK;Minissian MB;Wei J;Thomson LE;Berman DS;Shaw LJ;Petersen JW;Brown GH;Anderson RD;Shuster JJ;Cook-Wiens G;Rogatko A;Pepine CJ
在无阻塞性冠状动脉疾病（CAD）和冠状动脉微血管功能障碍（CMD）证据的患者中，心肌缺血症状和体征的机制基础尚不清楚。本研究的目的是机械测试短期晚钠电流抑制（雷诺嗪）在心绞痛，心肌灌注储备指数，舒张充盈这些科目。在有CMD证据[有创冠状动脉反应性试验或无创心脏磁共振成像心肌灌注储备指数（MPRI）]的受试者中进行的随机、双盲、安慰剂对照、交叉、机制试验。短期口服雷诺嗪500-1000 mg，每日两次，持续2周vs.安慰剂。通过西雅图心绞痛问卷（SAQ）和SAQ-7（共同主要）、日记心绞痛（次要）、负荷MPRI、舒张期充盈、生活质量（QoL）测量心绞痛。在128例（96%为女性）受试者中，未观察到结局的治疗差异。雷诺嗪给药期间，药物应激期间的峰值心率较低（-3.55 b. p.m.，P < 0.001）。SAQ-7的变化与MPRI的变化直接相关（相关系数0.25，P = 0.005）。MPRI的变化预测了SAQ QoL的变化，调整了体重指数（BMI），既往心肌梗死和部位（P = 0.0032）。低冠状动脉血流储备（CFR <2.5）组MPRI（P < 0.0137）、SAQ心绞痛频率（P = 0.027）和SAQ-7（P = 0.041）明显改善。在有症状的受试者中进行的这项机制试验中，无阻塞性CAD，短期晚期钠电流抑制对SAQ心绞痛通常无效。心绞痛和心肌灌注储备的变化是相关的，支持的概念，改善缺血的策略，应在这些科目进行测试。clinicaltrials.gov标识符：NCT 01342029。
The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling. Randomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500–1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (−3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041). In this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects. clinicaltrials.gov Identifier: NCT01342029.