Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with ranolazine

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Abstract

Background: Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine—a late sodium current inhibitor—improves diastolic function in animal models and subjects with obstructive coronary artery disease (CAD). Hypothesis: We hypothesized that ranolazine would beneficially alter diastolic function in CMD. Methods: To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD and from 43 healthy reference controls. Results: Diastolic strain rate was impaired in CMD vs controls (circumferential diastolic strain rate: 99.9% ± 2.5%/s vs 120.1% ± 4.0%/s, P = 0.0003; radial diastolic strain rate: −199.5% ± 5.5%/s vs −243.1% ± 9.6%/s, P = 0.0008, case vs control). Moreover, peak systolic circumferential strain (CS) and radial strain (RS) were also impaired in cases vs controls (CS: −18.8% ± 0.3% vs −20.7% ± 0.3%; RS: 35.8% ± 0.7% vs 41.4% ± 0.9%; respectively; both P < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis, however, we observed no significant changes in left ventricular diastolic function in CMD cases after 2 weeks of ranolazine vs placebo. Conclusions: The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have subclinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD.

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Nelson, M. D., Sharif, B., Shaw, J. L., Cook-Wiens, G., Wei, J., Shufelt, C., … Bairey Merz, C. N. (2017). Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with ranolazine. Clinical Cardiology, 40(5), 300–306. https://doi.org/10.1002/clc.22660

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