Cardiovascular Complications of Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

Cardiovascular Complications of Sickle Cell Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044901
• Other study ID #: 16653A
• Status: Completed
• Start date: March 2009
• Est. completion date: February 2021

Study information

• Verified date: February 2022
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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.

Locations

Country	Name	City	State
United States	University of Chicago Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	Parameter measured at baseline.
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.	median follow up 3 years