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Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular
Cecil A Rambarat1, Islam Y Elgendy1, Eileen M Handberg1
1Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, USA.
Insights
Ranolazine improved angina and myocardial perfusion in symptomatic patients with coronary microvascular dysfunction (CMD) and low coronary flow reserve (CFR). This suggests the late sodium channel is key in managing CMD.
Area of Science:
- Cardiology
- Pharmacology
- Medical Imaging
Background:
- A prior trial showed ranolazine did not improve angina or myocardial perfusion reserve index (MPRI) in symptomatic subjects without obstructive coronary artery disease (CAD).
- This prespecified substudy focused on patients with invasively assessed coronary flow reserve (CFR).
- Previous observations suggested lower CFR was associated with adverse outcomes and beneficial treatment responses.
Purpose of the Study:
- To investigate the clinical characteristics and myocardial perfusion responses to ranolazine in a subgroup of patients with invasively assessed CFR.
- To determine if ranolazine benefits patients with coronary microvascular dysfunction (CMD) defined by low CFR.
Main Methods:
- A randomized, double-blind, crossover trial of ranolazine versus placebo was conducted.
- Patients were subgrouped based on CFR (<2.5 vs ≥2.5).
- Symptoms were assessed using the Seattle Angina Questionnaire (SAQ-7), and left-ventricular volume and MPRI were measured by magnetic resonance imaging (MRI).
Main Results:
- 81 patients (98% women, mean age 55) with invasively determined CFR were analyzed.
- 43% of patients had a CFR <2.5.
- Patients with low CFR (<2.5) showed improved angina and midventricular MPRI with ranolazine compared to placebo. Reduced left-ventricular end-diastolic volume predicted a better angina response in the low CFR group.
Conclusions:
- Symptomatic patients with no obstructive CAD and low CFR (<2.5) experienced improved angina and myocardial perfusion with ranolazine.
- These findings support the role of the late sodium channel in managing coronary microvascular dysfunction (CMD).
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.