Cardiovascular Complications of Sickle Cell Disease

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT01044901
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Duration (Months): 143.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Procedure: MRI, Transthoracic Echocardiography, tonometry, EKG

Detailed Description

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 51 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Cardiovascular Complications of Sickle Cell Disease
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Feb 1, 2021
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
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).	Procedure: 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.; Other Names: electrocardiography Cardiac magnetic resonance Doppler trans-thoracic echocardiography
Healthy Volunteers 13 healthy control subjects were frequency matched to patients with SCD on age, sex, and race.	Procedure: 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.; Other Names: electrocardiography Cardiac magnetic resonance Doppler trans-thoracic echocardiography

Outcome Measures

Primary Outcome Measures

1. MRI Parameter - LVEDVi, mL/cm2 (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

2. MRI Parameter - LVESVi, mL/cm2 - (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

3. MRI Parameter - LV Mass Index, g/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

4. MRI Parameter - RVEDVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

5. MRI Parameter - RVESVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

6. MRI Parameter - LAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

7. MRI Parameter - RAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

8. MRI Parameter - LVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter measured at baseline.]

   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.

9. MRI Parameter - RVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges) [Parameter at baseline.]

   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.

10. MRI Parameter - Late Gadolinium Enhancement, Performed Via Visual Inspection, Normally None Should be Present [Parameter measured at baseline.]

    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.

11. MRI Parameter - Myocardial T2-star, ms, Performed Using Decay Curves (Normal >20ms) [Parameter measured at baseline.]

    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.

12. MRI Parameter - Hepatic T2-star, ms, Performed Using Decay Curves, Normal >18ms [Parameter at baseline.]

    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.

13. MRI Parameter - Myocardial Perfusion Reserve Index, Measured Using Upslope Technique. Control Subjects Available for Normal Ranges [Parameter measured at baseline.]

    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.

14. MRI Parameter - Diastolic Dysfunction, Determined According to American Society of Echocardiography Guidelines [Parameter measured at baseline.]

    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.

15. MRI Parameter - Lateral E/e', Measured Using Doppler Echo. Controls Available as Normal Ranges [Parameter measured at baseline.]

    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.

16. MRI Parameter - Augmentation Pressure, See Controls for Normal Ranges [Parameter measured at baseline.]

    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.

17. MRI Parameter - Augmentation Index, See Control Subjects for Normal Ranges [Parameter measured at baseline.]

    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.

18. MRI Parameter - Systemic Systolic Blood Pressure [Parameter measured at baseline.]

    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.

19. MRI Parameter - Systemic Diastolic Blood Pressure, mm Hg [Parameter measured at baseline.]

    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.

Secondary Outcome Measures

1. Genome-Wide Gene Expression and Targeted Genetic Polymorphisms in SCD Patients Linked to a Quantitative Noninvasive-based PH Phenotype. [median follow up 3 years]

   To detect genome-wide gene expression and targeted genetic polymorphisms in SCD patients linked to a quantitative noninvasive-based PH phenotype.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Medical Center	Chicago	Illinois	United States	60430

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Amit R Patel, M.D., University of Chicago

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Mar 19, 2009

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT01044901
• Other Study ID Numbers: 16653A
• First Posted: Jan 8, 2010
• Last Update Posted: Feb 23, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Chicago: Sickle Cell Disease; Cardiac magnetic resonance imaging; Coronary Disease; Pulmonary Hypertension
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

Participant Flow

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	38	13
COMPLETED	38	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	38	13	51
Age, Customized (years) [Median (Inter-Quartile Range) ]
Age	32	25	29
Sex: Female, Male (Count of Participants)
Female	21 55.3%	8 61.5%	29 56.9%
Male	17 44.7%	5 38.5%	22 43.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	38 100%	13 100%	51 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Body Surface Area (m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [m^2]	2.0	1.8	2.0

Outcome Measures

1. Primary Outcome

Title	MRI Parameter - LVEDVi, mL/cm2 (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [mL/cm2]	124.0 (26.8)	78.7 (11.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	MRI Parameter - LVESVi, mL/cm2 - (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Median (Inter-Quartile Range) [mL/cm2]	47	31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as median (interquartile range) based upon the Shapiro-Wilks test of normality, and then analyzed with a Wilcoxon (Mann-Whitney test).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	MRI Parameter - LV Mass Index, g/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [g/cm2]	77.2 (19.2)	51.6 (13.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments
	Method	t-test, 2 sided
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.

4. Primary Outcome

Title	MRI Parameter - RVEDVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [mL/cm2]	126.4 (27.7)	83.0 (13.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

5. Primary Outcome

Title	MRI Parameter - RVESVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [mL/cm2]	56.3 (17.1)	37.8 (7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

6. Primary Outcome

Title	MRI Parameter - LAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [mL/cm2]	64.8 (16.2)	41.1 (9.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

7. Primary Outcome

Title	MRI Parameter - RAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Median (Inter-Quartile Range) [mL/cm2]	76	52

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as median (interquartile range) based upon the Shapiro-Wilks test of normality, and then analyzed with a Wilcoxon (Mann-Whitney) test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Primary Outcome

Title	MRI Parameter - LVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Median (Inter-Quartile Range) [percentage of ejection fraction]	58	64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as median (interquartile range) based upon the Shapiro-Wilks test of normality, and then analyzed with a Wilcoxon (Mann-Whitney) test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Primary Outcome

Title	MRI Parameter - RVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
Description	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.
Time Frame	Parameter at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [percentage of ejection fraction]	56.1 (6.4)	55.4 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

10. Primary Outcome

Title	MRI Parameter - Late Gadolinium Enhancement, Performed Via Visual Inspection, Normally None Should be Present
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

Some parameters were unable to be collected from patients with Sickle Cell Disease.

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	32	13
Count of Participants [Participants]	8 21.1%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented as frequencies and percentages, and then analyzed with a Fisher exact test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Fisher Exact
	Comments

11. Primary Outcome

Title	MRI Parameter - Myocardial T2-star, ms, Performed Using Decay Curves (Normal >20ms)
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [ms]	41.6 (13.4)	38.4 (14.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

12. Primary Outcome

Title	MRI Parameter - Hepatic T2-star, ms, Performed Using Decay Curves, Normal >18ms
Description	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.
Time Frame	Parameter at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Median (Inter-Quartile Range) [ms]	10	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as median (interquartile range) based upon the Shapiro-Wilks test of normality, and then analyzed with a Wilcoxon (Mann-Whitney) test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Primary Outcome

Title	MRI Parameter - Myocardial Perfusion Reserve Index, Measured Using Upslope Technique. Control Subjects Available for Normal Ranges
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [index]	1.4 (0.3)	1.87 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

14. Primary Outcome

Title	MRI Parameter - Diastolic Dysfunction, Determined According to American Society of Echocardiography Guidelines
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

The measure was unable to be measured for some patients with Sickle Cell Disease.

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	35	13
Count of Participants [Participants]	10 26.3%	1 7.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented was as frequencies and percentages, and then analyzed with a Fisher exact test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Fisher Exact
	Comments

15. Primary Outcome

Title	MRI Parameter - Lateral E/e', Measured Using Doppler Echo. Controls Available as Normal Ranges
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Median (Inter-Quartile Range) [ratio]	7.2	6.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as median (interquartile range) based upon the Shapiro-Wilks test of normality, and then analyzed with a Wilcoxon (Mann-Whitney) test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0288
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

16. Primary Outcome

Title	MRI Parameter - Augmentation Pressure, See Controls for Normal Ranges
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Median (Inter-Quartile Range) [percentage of the pulse pressure]	9.0	2.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as median (interquartile range) based upon the Shapiro-Wilks test of normality, and then analyzed with a Wilcoxon (Mann-Whitney) test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	Wilcoxon (Mann-Whitney)
	Comments

17. Primary Outcome

Title	MRI Parameter - Augmentation Index, See Control Subjects for Normal Ranges
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [index]	23.6 (16.2)	12.5 (20.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

18. Primary Outcome

Title	MRI Parameter - Systemic Systolic Blood Pressure
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [mmHg]	122.3 (21.7)	132 (17.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

19. Primary Outcome

Title	MRI Parameter - Systemic Diastolic Blood Pressure, mm Hg
Description	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.
Time Frame	Parameter measured at baseline.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	38	13
Mean (Standard Deviation) [mmHg]	68.3 (18.1)	74.9 (16.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects With Sickle Cell Disease (SCD), Healthy Volunteers
	Comments	Primary outcome was presented at baseline as mean +/- standard deviation based upon the Shapiro-Wilks test of normality, and then analyzed with a Student t-test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments	P-values are not adjusted for multiple comparisons. Tests were two-tailed, considered statistically significant with a p-value <0.05.
	Method	t-test, 2 sided
	Comments

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All efforts were taken to gather all possible data but none were obtained for this Outcome Measure.

Arm/Group Title	Subjects With Sickle Cell Disease (SCD)	Healthy Volunteers
Arm/Group Description	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.	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.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse event data was collected over 3 years.
Arm/Group Title	Subjects With Sickle Cell Disease (SCD)		Healthy Volunteers
Arm/Group Description	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.		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.
All Cause Mortality
	Subjects With Sickle Cell Disease (SCD)		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/38 (7.9%)		0/13 (0%)
Serious Adverse Events
	Subjects With Sickle Cell Disease (SCD)		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Subjects With Sickle Cell Disease (SCD)		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/13 (0%)

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.