Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
JACC Cardiovasc Imaging. 2009 Nov;2(11):1301-9. doi: 10.1016/j.jcmg.2009.09.006.
This study examined the hypothesis that the improvement in myocardial blood flow (MBF) with ranolazine therapy could be detected by serial automated quantitative myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) and myocardial ischemia.
Myocardial ischemia enhances late sodium current, which then causes cellular calcium overload leading to mechanical left ventricular dysfunction and arrhythmias. Ranolazine inhibits late sodium current and improves diastolic tension and MBF in the animal model.
In this open-label, nonrandomized pilot study, we recruited 20 patients with known or a high probability of CAD and who had reversible perfusion defects on exercise treadmill gated single-photon emission computed tomography MPI while receiving conventional antianginal therapy. Ranolazine (up to 1,000 mg twice daily) was added to baseline therapy and a repeat treadmill MPI was obtained after 4 weeks. The extent and severity of total and reversible left ventricular perfusion abnormality (based on polar maps and a 17-segment model) were determined quantitatively using automated methods.
We screened 100 patients for 27 potential candidates; 5 declined and 2 did not complete the follow-up study. The mean age of the remaining 20 patients was 64 +/- 9 years; 30% were women and 50% had diabetes mellitus. The exercise time increased (425 +/- 105 s vs. 393 +/- 116 s, p = 0.017), and angina improved in 15 (75%) patients after ranolazine treatment. In the entire cohort, summed stress scores (10 +/- 7 vs. 13 +/- 8, p = 0.04) and summed difference scores (4.7 +/- 4 vs. 7.4 +/- 5, p = 0.0037) decreased at follow-up. An improvement in perfusion pattern and severity was noted in 14 (70%) patients. In these patients, the polar maps showed a decrease in total abnormality from 26 +/- 17% to 19 +/- 15% and a decrease in the reversible abnormality from 16 +/- 10% to 8 +/- 6% (all p values <0.05).
In this preliminary hypothesis-driven study, short-term ranolazine therapy was shown to improve myocardial perfusion and decrease the ischemic burden in patients with CAD.
本研究旨在检验以下假设，即在冠状动脉疾病（CAD）和心肌缺血患者中，通过连续的自动定量心肌灌注成像（MPI），可以检测到雷诺嗪治疗引起的心肌血流（MBF）改善。
心肌缺血增强晚期钠电流，进而导致细胞内钙超载，导致左心室机械功能障碍和心律失常。雷诺嗪抑制晚期钠电流，改善动物模型的舒张张力和 MBF。
在这项开放标签、非随机的初步研究中，我们招募了 20 名已知或高度疑似 CAD 患者，这些患者在接受常规抗心绞痛治疗时，运动平板门控单光子发射计算机断层扫描 MPI 显示有可逆灌注缺陷。在基线治疗的基础上添加雷诺嗪（最高 1000mg，每日两次），并在 4 周后进行重复平板运动 MPI。使用自动方法定量确定基于极坐标图和 17 节段模型的总左心室灌注异常和可逆性左心室灌注异常的程度和严重程度。
我们对 100 名患者进行了筛查，确定了 27 名潜在候选者；5 人拒绝，2 人未完成随访研究。其余 20 名患者的平均年龄为 64 ± 9 岁；30%为女性，50%患有糖尿病。雷诺嗪治疗后，15 名（75%）患者的运动时间增加（425 ± 105s 比 393 ± 116s，p = 0.017），心绞痛得到改善。在整个队列中，总和应激评分（10 ± 7 比 13 ± 8，p = 0.04）和总和差异评分（4.7 ± 4 比 7.4 ± 5，p = 0.0037）在随访时降低。14 名（70%）患者的灌注模式和严重程度得到改善。在这些患者中，极坐标图显示总异常从 26 ± 17%降至 19 ± 15%，可逆异常从 16 ± 10%降至 8 ± 6%（所有 p 值均<0.05）。
在这项初步的假设驱动研究中，短期雷诺嗪治疗可改善 CAD 患者的心肌灌注并减少缺血负荷。
