Cecil A Rambarat1, Islam Y Elgendy1, Eileen M Handberg1, C Noel Bairey Merz2, Janet Wei2, Margo B Minissian2, Michael D Nelson2, Louise E J Thomson3, Daniel S Berman3, Leslee J Shaw4, Galen Cook-Wiens5, Carl J Pepine6. 1. Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, USA. 2. Barbara Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, USA. 3. Departments of Medicine and Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 4. Program in Cardiovascular Outcomes Research and Epidemiology, Emory University, Atlanta, GA, USA. 5. Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 6. Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, USA. Electronic address: carl.pepine@medicine.ufl.edu.
Abstract
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.
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.
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