title: Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with ranolazine.
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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Applied Physiology and Advanced Imaging Laboratory, University of Texas at Arlington, Arlington, Texas.|Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.|Barbra Streisand Women's Heart Center, Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nelson
authors.affiliation: Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Behzad
authors.initials: B
authors.lastname: Sharif
authors.affiliation: Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Shaw
authors.affiliation: Biostatistics Core, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Galen
authors.initials: G
authors.lastname: Cook-Wiens
authors.affiliation: Barbra Streisand Women's Heart Center, Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Janet
authors.initials: J
authors.lastname: Wei
authors.affiliation: Barbra Streisand Women's Heart Center, Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Chrisandra
authors.initials: C
authors.lastname: Shufelt
authors.affiliation: Barbra Streisand Women's Heart Center, Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Emory Women's Heart Center, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Puja K
authors.initials: PK
authors.lastname: Mehta
authors.affiliation: Mark S. Taper Imaging Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Louise E J
authors.initials: LEJ
authors.lastname: Thomson
authors.affiliation: Emory Women's Heart Center, Emory University School of Medicine, Atlanta, Georgia.|Mark S. Taper Imaging Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Berman
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Thompson
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Handberg
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.affiliation: Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Debiao
authors.initials: D
authors.lastname: Li
authors.affiliation: Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: C Noel
authors.initials: CN
authors.lastname: Bairey Merz
mesh_terms: D000328:Adult; D000368:Aged; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D003971:Diastole; D005260:Female; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008833:Microcirculation; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D000069458:Ranolazine / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D026941:Sodium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents; D026941:Sodium Channel Blockers; D000069458:Ranolazine
keywords: Coronary microvascular dysfunction; microvascular ischemia; ranolazine; tissue tracking