title: Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy.
abstract: BACKGROUND
  Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms.
  
  
  RESULTS
  Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m(2)), right ventricle (127±28 vs 83±14 mL/m(2)), left atrium (65±16 vs 41±9 mL/m(2)), and right atrium (78±17 vs 56±17 mL/m(2); P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e', 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all).
  
  
  CONCLUSIONS
  Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01044901.
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Ankit A
authors.initials: AA
authors.lastname: Desai
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, IL.
authors.forename: Amit R
authors.initials: AR
authors.lastname: Patel
authors.affiliation: Department of Medicine, Ochsner Clinic, New Orleans, LA.
authors.forename: Homaa
authors.initials: H
authors.lastname: Ahmad
authors.affiliation: Department of Pathology, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: John V
authors.initials: JV
authors.lastname: Groth
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, IL.
authors.forename: Thejasvi
authors.initials: T
authors.lastname: Thiruvoipati
authors.affiliation: Department of Medicine, Loyola Medical Center, Maywood, IL.
authors.forename: Kristen
authors.initials: K
authors.lastname: Turner
authors.affiliation: Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chattanong
authors.initials: C
authors.lastname: Yodwut
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, IL.
authors.forename: Peter
authors.initials: P
authors.lastname: Czobor
authors.affiliation: Unity Point Health, Des Moines, IA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Artz
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
authors.affiliation: Department of Medicine, University of Arizona, Phoenix, AZ.
authors.forename: Joe G N
authors.initials: JGN
authors.lastname: Garcia
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, IL.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lang
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000473:pathology*; D009202:Cardiomyopathies / Q000150:complications / Q000473:pathology*; D015331:Cohort Studies; D003287:Contrast Media; D004452:Echocardiography / Q000379:methods; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male
chemical_list: D003287:Contrast Media; C064925:gadodiamide; D019786:Gadolinium DTPA
keywords: anemia, sickle cell; cardiomyopathies; fibrosis; myocardial perfusion imaging