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

• Type of Material: Article
• Authors: Michael D. Nelson, University of Texas Arlington; Behzad Sharif, Cedars-Sinai Medical Center; Jaime L. Shaw, Cedars-Sinai Medical Center; Galen Cook-Wiens, Cedars-Sinai Medical Center; Janet Wei, Cedars-Sinai Medical Center; Chrisandra Shufelt, Cedars-Sinai Medical Center; Puja Kiran Mehta, Emory University; Louise E.J. Thomson, Cedars-Sinai Medical Center; Daniel S. Berman, Emory University; Richard B. Thompson, University of Alberta; Eileen M. Handberg, University of Florida; Carl J. Pepine, University of Florida; Debiao Li, Cedars-Sinai Medical Center; C. Noel Bairey Merz, Cedars-Sinai Medical Center
• Language: English
• Date: 2017-05-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/clc.22660
• Title of Journal or Parent Work: Clinical Cardiology
• ISSN: 0160-9289
• Volume: 40
• Issue: 5
• Start Page: 300
• End Page: 306
• Grant/Funding Information: This work was supported by an unrestricted research grant from Gilead and by the American Heart Association (16SDG27260115), the Harry S. Moss Heart Trust, the National Heart, Lung and Blood Institute (N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164), a GCRC grant MO1-RR00425 from the National Center for Research Resources, the National Center for Research Resources, grant UL1RR033176, the NIH/National Center for Advancing Translational Sciences (NCATS), UCLA CTSI grant UL1TR000124 and UF CTSI grant UL1TR001427, grant R01 HL089765, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey, the Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California, the Edythe L. Broad Women's Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California, the Constance Austin Women's Heart Research Fellowship, the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, and the Erika Glazer Women's Heart Health Project, Cedars-Sinai Medical Center, Los Angeles.
• Keywords: CARDIOVASCULAR MAGNETIC-RESONANCE; Coronary microvascular dysfunction; EJECTION FRACTION; microvascular ischemia; DIASTOLIC DYSFUNCTION; Science & Technology; CONTROLLED-TRIAL; HEART-FAILURE; ranolazine; FEATURE TRACKING; PROGNOSTIC VALUE; Cardiac & Cardiovascular Systems; CHRONIC ANGINA-PECTORIS; ARTERY-DISEASE; Life Sciences & Biomedicine; ISCHEMIA-SYNDROME-EVALUATION; Cardiovascular System & Cardiology; tissue tracking
• Research Categories: Biology, Physiology; Health Sciences, General

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.