title: Left Ventricular Tonic Contraction as a Novel Biomarker of Cardiomyopathy in Duchenne Muscular Dystrophy.
abstract: Dilated cardiomyopathy (DCM) inevitably afflicts patients with Duchenne muscular dystrophy (DMD) as a consequence of cell death induced by unguarded calcium influx into cardiomyocytes. This mechanism may also inhibit muscle relaxation in early stages of cardiomyopathy. ACE inhibition (ACEi) is known to delay the onset and slow the progression of DCM in DMD. The objective of this study is to use echocardiography to assess for preclinical cardiac changes consistent with intracellular calcium dysregulation before the onset of overt ventricular dysfunction, and to evaluate how prophylactic ACEi may alter these pre-cardiomyopathic changes in the pediatric DMD population. We examined 263 echocardiograms from 70 pediatric patients with DMD. We defined abnormal tonic contraction (TC) as left ventricular internal dimension in diastole (LVIDd) Z-score < -1.5. In our cohort, we found that TC is detectable as early as 8 years of age, and most commonly affects patients between 11 and 15 years. This effect was independent of LV mass and systolic function. Prophylactic ACEi decreased the incidence of TC (p = 0.007) and preserved cardiac function (p < 0.0001). Left ventricular TC often precedes DCM in DMD, most commonly affecting the 11- to 15-year-old age range. TC is not related to ventricular hypertrophy, but rather may be a clinical correlate of the "calcium hypothesis" of DMD pathophysiology. LV TC is thus a promising biomarker for early detection of cardiomyopathy in DMD. ACEi prophylaxis suppresses LV TC and delays the development of DCM in DMD.
authors.affiliation: Division of Cardiology at Children's Hospital of Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. jsu@chla.usc.edu.|Children's Hospital of Los Angeles, 4650 W. Sunset Blvd, Mailstop #34, Los Angeles, CA, 90027, USA. jsu@chla.usc.edu.
authors.forename: Jennifer A
authors.identifier: http://orcid.org/0000-0002-7749-0912
authors.initials: JA
authors.lastname: Su
authors.affiliation: Children's Hospital of Los Angeles, 4650 W. Sunset Blvd, Mailstop #34, Los Angeles, CA, 90027, USA.|Division of Neurology at Children's Hospital of Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Ramos-Platt
authors.affiliation: Division of Cardiology at Children's Hospital of Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Children's Hospital of Los Angeles, 4650 W. Sunset Blvd, Mailstop #34, Los Angeles, CA, 90027, USA.
authors.forename: JonDavid
authors.initials: J
authors.lastname: Menteer
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications*; D012189:Retrospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers
keywords: ACE inhibition; Biomarker; Dilated cardiomyopathy; Duchenne muscular dystrophy; Pediatrics; Prophylaxis