title: Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease.
abstract: OBJECTIVE
  The aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD).
  
  
  BACKGROUND
  Cardiopulmonary complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings.
  
  
  METHODS
  In a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD.
  
  
  RESULTS
  In the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present (z-score 3.1, p = 0.002), shortening fraction was normal (37.6 ± 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e') were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e' correlated with enlarged left atrial volume in SCD (p = 0.003 and p = 0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology.
  
  
  CONCLUSIONS
  Patients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality rates and sudden death seen in patients with SCD with mildly elevated TRV.
authors.affiliation: Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: omar.niss@cchmc.org.
authors.forename: Omar
authors.initials: O
authors.lastname: Niss
authors.affiliation: Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Quinn
authors.affiliation: Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Adam
authors.initials: A
authors.lastname: Lane
authors.affiliation: Division of Cardiology, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Joshua
authors.initials: J
authors.lastname: Daily
authors.affiliation: Division of Cardiology, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Khoury
authors.affiliation: Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Nihal
authors.initials: N
authors.lastname: Bakeer
authors.affiliation: Division of Cardiology, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kimball
authors.affiliation: Division of Cardiology, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.affiliation: Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Punam
authors.initials: P
authors.lastname: Malik
authors.affiliation: Division of Cardiology, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D062186:Arterial Pressure; D016279:Atrial Function, Left; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology*; D002648:Child; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D011667:Pulmonary Veins / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D014261:Tricuspid Valve / Q000503:physiopathology; D014690:Venous Pressure; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology; D016278:Ventricular Function, Right
keywords: cardiomyopathy; pulmonary hypertension; restrictive physiology; sickle cell disease