TY - JOUR
T1 - Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction
T2 - Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction ancillary study
AU - Rambarat, Cecil A.
AU - Elgendy, Islam Y.
AU - Handberg, Eileen M.
AU - Bairey Merz, C. Noel
AU - Wei, Janet
AU - Minissian, Margo B.
AU - Nelson, Michael D.
AU - Thomson, Louise E.J.
AU - Berman, Daniel S.
AU - Shaw, Leslee J.
AU - Cook-Wiens, Galen
AU - Pepine, Carl J.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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
AB - 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
KW - Angina
KW - Coronary microvascular dysfunction
KW - Late sodium channel inhibition
UR - http://www.scopus.com/inward/record.url?scp=85054537929&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2018.09.081
DO - 10.1016/j.ijcard.2018.09.081
M3 - Article
C2 - 30293664
AN - SCOPUS:85054537929
SN - 0167-5273
VL - 276
SP - 8
EP - 13
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -