title: Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy.
abstract: BACKGROUND
  Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE).
  
  
  METHODS
  Thirty-one DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed in all participants before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test.
  
  
  RESULTS
  The DMD participants had significantly higher mean native T1 compared with controls (1045 ms vs. 988 ms, p = 0.001). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1039 ms vs. 988 ms, p = 0.002, and 1038 ms vs. 988 ms, p = 0.011). DMD participants had a significantly greater mean ECV than controls (0.31 vs. 0.24, p < 0.001), even in the settings of normal LVEF (0.28 vs. 0.24, p < 0.001) and negative LGE (0.29 vs. 0.24, p = 0.001).
  
  
  CONCLUSIONS
  DMD participants have elevated LV myocardial native T1 and ECV, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials.
authors.affiliation: Thomas P Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way Suite 5230, Doctors' Office Tower, Nashville, TN, 37232-9119, USA. Jonathan.h.soslow@vanderbilt.edu.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Soslow
authors.affiliation: Department of Electrical Engineering and Computer Sciences, Vanderbilt University, Nashville, TN, USA. Stephen.m.damon@vanderbilt.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Damon
authors.affiliation: Thomas P Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way Suite 5230, Doctors' Office Tower, Nashville, TN, 37232-9119, USA. Kimberly.crum@vanderbilt.edu.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Crum
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Mark.lawson@vanderbilt.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lawson
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA. James.c.slaughter@vanderbilt.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA. Meng.xu@vanderbilt.edu.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA. araia@nih.gov.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Arai
authors.affiliation: Department of Cardiac Services, Maine Medical Center, Portland, ME, USA. Dsawyer@mmc.org.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sawyer
authors.affiliation: Thomas P Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way Suite 5230, Doctors' Office Tower, Nashville, TN, 37232-9119, USA. David.parra@vanderbilt.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Parra
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. Bruce.damon@vanderbilt.edu.|Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA. Bruce.damon@vanderbilt.edu.|Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA. Bruce.damon@vanderbilt.edu.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Damon
authors.affiliation: Thomas P Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way Suite 5230, Doctors' Office Tower, Nashville, TN, 37232-9119, USA. Larry.markham@vanderbilt.edu.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Markham
mesh_terms: D000293:Adolescent; D000328:Adult; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D003287:Contrast Media; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000175:diagnosis; D009206:Myocardium / Q000473:pathology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013318:Stroke Volume; D016277:Ventricular Function, Left; D055815:Young Adult
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA