Novel Cardiac Magnetic Resonance Imaging to Define a Unique Restrictive Cardiomyopathy in Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Cardiomyopathies; Cardiomyopathy, Restrictive; Anemia, Sickle Cell
Study type: Observational

Summary: 
      The purpose of this study is to use cardiac magnetic resonance imaging (CMR) and
      echocardiographic tissue Doppler imaging to demonstrate a unique restrictive cardiomyopathy
      of sickle cell disease. The investigators will characterize its frequency and how it might
      change (e.g., presence/absence and severity) over a 2-year period.
    

Detailed description: 
      Sickle cell disease (SCD) causes progressive cardiopulmonary morbidity, beginning in
      childhood, which can ultimately be fatal. As a group, cardiopulmonary complications, such as
      acute chest syndrome and sudden death, are now the most common causes of death in SCD,
      especially in adolescents and adults.

      Patients with SCD have features of both an anemia-related, high cardiac output state and a
      restrictive cardiomyopathy (RCM). The investigators propose that this unique RCM is an
      overlooked and understudied complication of SCD. RCM could explain the modest increases in
      pulmonary artery pressure in patients with SCD, as measured by cardiac catheterization or
      estimated by tricuspid regurgitant jet velocity (TRJV), which has often been attributed to a
      primary pulmonary arterial hypertension (PAH). RCM could also be the cause of unexplained
      sudden cardiac death in SCD, which is a feature of other forms of RCM.

      The investigators overarching hypothesis is that increased reactive oxygen species
      (ROS)-mediated angiotensin-1 receptor (AT1R)-TGFβ1 signaling is pro-fibrotic and, in
      combination with vaso-occlusive ischemia-reperfusion injury, results in an age-dependent,
      progressive RCM that can be detected by non-invasive cardiac imaging.

      This pilot, longitudinal, observational study uses a novel, comprehensive, multimodal cardiac
      imaging strategy, combining cutting-edge cardiac magnetic resonance imaging (CMR) and
      echocardiographic tissue Doppler imaging (TDI), to demonstrate the unique RCM of SCD,
      characterizing its frequency and the temporal evolution over a 2-year period. The
      investigators will also correlate the RCM phenotype with biomarkers of ROS and renin
      angiotensin system (RAS)-TGFβ1 signaling.

      This research could change the investigators understanding of how SCD affects the heart and
      lungs. The investigators propose studies that will change the current concept of primary
      pulmonary vasculopathy to a cardiomyopathy-centered model with secondary pulmonary vascular
      changes leading to sudden death. This translational pilot study will deliver a novel, clear,
      quantifiable CMR phenotype with established diagnostic performance that will be used in phase
      II/III clinical trials to test anti-fibrotic therapy to prevent or reverse SCD-related RCM.
    

Intervention name(s): Cardiac magnetic resonance imaging (CMR)
Intervention type(s): Other
Intervention description(s): CMR is obtained on all participants in all arms/groups
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Enrolling a maximum of 40 participants in the entire study across four age strata: A, 6 -
        13.9 years; B, 14 - 20.9 years; C, 21 years and older; and D, 6 years and older.
      
Biospecimen description: 
      Blood, DNA, and urine specimens.
    
Keywords: Sickle Cell Disease (SCD); Cardiac Magnetic Resonance Imaging (CMR); Cardiomyopathy; Pulmonary Hypertension