Cardiovascular Complications of Sickle Cell Disease

Study Overview
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Brief Summary
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In this research study, we are using heart imaging exams and blood testing, in order to gain an improved understanding of the pulmonary (lung) hypertension and cardiovascular (heart) complications that often occur in sickle cell patients. Information gathered from the healthy volunteers that participate in this study will be compared to information from the sickle cell patients in this study in order to help further our understanding.

Detailed Description
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Cardiac magnetic resonance (CMR) has gained increasing clinical application in cardiopulmonary diseases. Due to its 3-dimensional nature, CMR is considered the gold-standard for quantifying left and right ventricular systolic function and size. Additionally, its high tissue contrast allows for a detailed characterization of myocardial tissue. Specifically, the use of techniques such as late gadolinium enhancement can be used to detect the presence of tiny amounts of myocardial scar. Other techniques have been shown to correlate strongly with myocardial iron content. Just as importantly, CMR perfusion imaging can accurately quantify myocardial blood flow and can provide tremendous insight into the function of the microcirculation. CMR's high spatial and temporal resolution, its 3-dimensional approach, its ability to characterize the tissue, and its ability to evaluate the micro- and macro-circulation make it a comprehensive technique for the evaluation of heart disease. Recently, one CMR study has already shown the presence of cardiac microvascular disease in a subset of adult sickle cell disease (SCD) patients in the absence of infarcted myocardium, myocardial iron overload, or coronary artery disease, increasing the evidence for the contribution of left heart disease to pulmonary hypertension (PH) development in these patients; unfortunately, strong conclusions could not be made because the study was underpowered. Thus, this proposal will leverage the advantages offered by CMR to better characterize and detect the PH and cardiopulmonary subphenotypes in the SCD patient population.

Official Title
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Cardiovascular Complications of Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Procedure: MRI, Transthoracic Echocardiography, tonometry, EKG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be 18+ Patients who were diagnosed with SCD confirmed by high-pressure liquid chromatography or hemoglobin electrophoresis will be eligible for the study Only patients in stable condition will be included Patients receiving transfusions will not be excluded Exclusion Criteria: Patients with vaso-occlusive crises or an episode of acute chest syndrome within the previous four weeks (after 4 weeks have passed, the patients may be re-evaluated for eligibility) Patients with high degree heart block; active, hemodynamically significant, ventricular arrhythmias; unstable coronary syndromes; history of myocardial infarction within 1 month of the study. Contraindications to gadolinium-enhanced magnetic resonance examination such as severe claustrophobia, Pacemaker, defibrillators, cerebral aneurysm clips, or neurostimulator. Pregnancy Patients with sinus node dysfunction

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects with Sickle Cell Disease (SCD)<br>38 clinically stable black patients with Sickle Cell Disease (SCD) (including individuals with hemoglobin SS, SC, and β-thalassemia demonstrated by high-performance liquid chromatographic separation or gel electrophoresis). | Procedure: MRI, Transthoracic Echocardiography, tonometry, EKG<br>* Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures.<br>* Other names: Doppler trans-thoracic echocardiography;|
| Healthy Volunteers<br>13 healthy control subjects were frequency matched to patients with SCD on age, sex, and race. | Procedure: MRI, Transthoracic Echocardiography, tonometry, EKG<br>* Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures.<br>* Other names: Doppler trans-thoracic echocardiography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI Parameter - LVEDVi, mL/cm2 (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - LVESVi, mL/cm2 - (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - LV Mass Index, g/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - RVEDVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - RVESVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - LAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - RAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - LVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - RVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter at baseline. | 
| MRI Parameter - Late Gadolinium Enhancement, Performed Via Visual Inspection, Normally None Should be Present | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Myocardial T2-star, ms, Performed Using Decay Curves (Normal >20ms) | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Hepatic T2-star, ms, Performed Using Decay Curves, Normal >18ms | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter at baseline. | 
| MRI Parameter - Myocardial Perfusion Reserve Index, Measured Using Upslope Technique. Control Subjects Available for Normal Ranges | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Diastolic Dysfunction, Determined According to American Society of Echocardiography Guidelines | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Lateral E/e', Measured Using Doppler Echo. Controls Available as Normal Ranges | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Augmentation Pressure, See Controls for Normal Ranges | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Augmentation Index, See Control Subjects for Normal Ranges | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Systemic Systolic Blood Pressure | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 
| MRI Parameter - Systemic Diastolic Blood Pressure, mm Hg | Comprehensively and quantitatively characterized the cardiopulmonary complications of SCD and gained an improved understanding of the pathophysiology of pulmonary hypertension and diastolic dysfunction in patients with Sickle Cell Disease. | Parameter measured at baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genome-Wide Gene Expression and Targeted Genetic Polymorphisms in SCD Patients Linked to a Quantitative Noninvasive-based PH Phenotype. | To detect genome-wide gene expression and targeted genetic polymorphisms in SCD patients linked to a quantitative noninvasive-based PH phenotype. | median follow up 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Cardiac magnetic resonance imaging, Coronary Disease, Pulmonary Hypertension