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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects with Sickle Cell Disease (SCD) | 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). |
| |
| Healthy Volunteers | 13 healthy control subjects were frequency matched to patients with SCD on age, sex, and race. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MRI, Transthoracic Echocardiography, tonometry, EKG | Procedure | Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. |
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Subjects will be recruited from clinics at the University of Chicago as well as from the community via flyers posted at the University of Chicago and a web site posted on the University of Chicago Medical Center web site.
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| Name | Affiliation | Role |
|---|---|---|
| Amit R Patel, M.D. | University of Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Medical Center | Chicago | Illinois | 60430 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24676783 | Result | Desai AA, Patel AR, Ahmad H, Groth JV, Thiruvoipati T, Turner K, Yodwut C, Czobor P, Artz N, Machado RF, Garcia JGN, Lang RM. Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy. Circ Cardiovasc Imaging. 2014 May;7(3):430-437. doi: 10.1161/CIRCIMAGING.113.001420. Epub 2014 Mar 27. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Subjects With Sickle Cell Disease (SCD) | 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). MRI, Transthoracic Echocardiography, tonometry, EKG: Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. |
| FG001 | Healthy Volunteers | 13 healthy control subjects were frequency matched to patients with SCD on age, sex, and race. MRI, Transthoracic Echocardiography, tonometry, EKG: Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Subjects With Sickle Cell Disease (SCD) | 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). MRI, Transthoracic Echocardiography, tonometry, EKG: Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | mL/cm2 | Parameter measured at baseline. |
|
Adverse event data was collected over 3 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Subjects With Sickle Cell Disease (SCD) | 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). MRI, Transthoracic Echocardiography, tonometry, EKG: Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. |
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Due to small sample size, caution should be considered in applying these results to all patients with SCD, in particular to those with genotypes outside of hemoglobin and those with a recent or ongoing crisis. Not all patients had evaluable data sets for all of the cardiovascular tests, due to inadequate venous access, frequently encountered in patients with SCD. Finally, our follow-up period is currently too short to make meaningful comments on outcomes such as mortality and functional status.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Amit Patel, MD | The University of Chicago | 773-702-9461 | apatel2@medicine.bsd.uchicago.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Mar 19, 2009 | Feb 6, 2022 | Prot_SAP_ICF_001.pdf |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D003327 | Coronary Disease |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D009682 | Magnetic Resonance Spectroscopy |
| D008365 | Manometry |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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We will study blood samples for chemicals related to sickle cell and heart and lung disease, and will be evaluating DNA for purposes of the study.
|
| 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. |
| BG001 | Healthy Volunteers | 13 healthy control subjects were frequency matched to patients with SCD on age, sex, and race. MRI, Transthoracic Echocardiography, tonometry, EKG: Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Body Surface Area | Median | Inter-Quartile Range | m^2 |
|
| OG001 | Healthy Volunteers | 13 healthy control subjects were frequency matched to patients with SCD on age, sex, and race. MRI, Transthoracic Echocardiography, tonometry, EKG: Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. |
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| Primary | 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. | Posted | Median | Inter-Quartile Range | mL/cm2 | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | g/cm2 | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | mL/cm2 | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | mL/cm2 | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | mL/cm2 | Parameter measured at baseline. |
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| Primary | 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. | Posted | Median | Inter-Quartile Range | mL/cm2 | Parameter measured at baseline. |
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| Primary | 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. | Posted | Median | Inter-Quartile Range | percentage of ejection fraction | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | percentage of ejection fraction | Parameter at baseline. |
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| Primary | 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. | Some parameters were unable to be collected from patients with Sickle Cell Disease. | Posted | Count of Participants | Participants | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | ms | Parameter measured at baseline. |
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| Primary | 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. | Posted | Median | Inter-Quartile Range | ms | Parameter at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | index | Parameter measured at baseline. |
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| Primary | 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. | The measure was unable to be measured for some patients with Sickle Cell Disease. | Posted | Count of Participants | Participants | Parameter measured at baseline. |
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| Primary | 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. | Posted | Median | Inter-Quartile Range | ratio | Parameter measured at baseline. |
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| Primary | 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. | Posted | Median | Inter-Quartile Range | percentage of the pulse pressure | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | index | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | mmHg | Parameter measured at baseline. |
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| Primary | 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. | Posted | Mean | Standard Deviation | mmHg | Parameter measured at baseline. |
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| Secondary | 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. | All efforts were taken to gather all possible data but none were obtained for this Outcome Measure. | Posted | median follow up 3 years |
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| 3 |
| 38 |
| 0 |
| 38 |
| 0 |
| 38 |
| EG001 | Healthy Volunteers | 13 healthy control subjects were frequency matched to patients with SCD on age, sex, and race. MRI, Transthoracic Echocardiography, tonometry, EKG: Unless contraindicated, subjects will receive Regadenoson and Gadolinium contrast agent during the Cardiac magnetic resonance. The tonometer, EKG, and echo are non-invasive procedures. | 0 | 13 | 0 | 13 | 0 | 13 |
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| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |