Relationship Between Abnormal Myocardial Perfusion and Diastolic Dysfunction in Sickle Cell Disease Using PET

Study Overview
=================
Brief Summary
-----------------
There is limited information on what causes injury to the heart in individuals with Sickle Cell Disease (SCD). Researchers in this study want to see if decreased blood flow to the heart during stress could be causing the heart damage seen in SCD patients. They also want to test people who don't have SCD to see if their hearts react the same way under stress. Primary Objective To estimate the coronary flow reserve (CFR) (also referred to as myocardial perfusion reserve), as measured by PET stress-rest myocardial perfusion imaging, in SCD patients with and without diastolic dysfunction, and healthy controls. Secondary Objectives To investigate the relationship between decreased CFR (quantified with PET stress- rest myocardial perfusion imaging) and presence of abnormal diastolic parameters

Detailed Description
-----------------
This study requires two visits. The first visit includes blood tests, an electrocardiogram (EKG), and an echocardiogram. The second visit includes a positron emission tomography (PET) stress test and a blood test. Subjects will be considered off-study one week after all post PET imaging study tests have been completed along with the next day and one-week follow-up phone calls are completed.

Official Title
-----------------
An Evaluation of the Relationship Between Abnormal Myocardial Perfusion and Diastolic Dysfunction in Sickle Cell Disease Using PET (Stress-Rest) Myocardial Perfusion Imaging (MYPERS)

Conditions
-----------------
Sickle Cell Disease

Intervention / Treatment
-----------------
* Drug: [13N]NH3
* Drug: Lexiscan
* Diagnostic Test: Positron emission tomography


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria - Stratum A: Sickle cell patients with diastolic dysfunction 18 to 21 years of age Black Diagnosis of SCD of HbSS and HbSβ0thalassemia genotypes Three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography) Inclusion Criteria - Stratum B: Sickle cell patients without diastolic dysfunction 18 to 21 years of age Black Diagnosis of SCD of HbSS and HbSβ0thalassemia genotypes Two or less abnormal diastolic parameters Inclusion Criteria - Stratum C: Healthy controls 18 to 21 years of age Black Two or less abnormal diastolic parameters Exclusion Criteria - Stratum A: Recent hospitalization for vaso-occlusive pain crisis or acute chest syndrome in last 4 weeks Blood transfusion in the last 3 months Individuals with signs, symptoms or EKG findings of acute myocardial ischemia, infarction or unstable angina Individuals with history of VT/VF or SVT Previous cardiac surgery Known congenital heart disease (other than patent ductus arteriosus or Atrial septal defect) Stenotic valvular disease or left main coronary artery stenosis History of myo/pericarditis Left ventricle systolic dysfunction Cardiovascular instability/uncontrolled hypertension (h/o hypertensive urgency or emergency) History of sinus node dysfunction or high grade AV nodal block History of aborted sudden cardiac death or cardiac arrest Current seizure disorder on AED Pregnant/Breast-feeding Any medical or social reason, which, in the opinion of the principal investigators would make the participation of the subject ill-advised. Exclusion Criteria - Stratum B: Diagnosed with three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography) Recent hospitalization for vaso-occlusive pain crisis or acute chest syndrome in last 4 weeks Blood transfusion in the last 3 months Individuals with signs, symptoms or EKG findings of acute myocardial ischemia, infarction or unstable angina Individuals with history of VT/VF or SVT Previous cardiac surgery Known congenital heart disease (other than patent ductus arteriosus or Atrial septal defect) Stenotic valvular disease or left main coronary artery stenosis History of myo/pericarditis Left ventricle systolic dysfunction Cardiovascular instability/uncontrolled hypertension (h/o hypertensive urgency or emergency) History of sinus node dysfunction or high-grade AV nodal block History of aborted sudden cardiac death or cardiac arrest Current seizure disorder on AED Pregnant/Breast-feeding Any medical or social reason, which, in the opinion of the principal investigators would make the participation of the subject ill-advised. Exclusion Criteria - Stratum C: All genotypes of SCD Diagnosed with three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography) Individual with hemoglobin level below the normal range for that age and sex Individuals with signs, symptoms or EKG findings of acute myocardial ischemia, infarction or unstable angina Individuals with history of VT/VF or SVT Previous cardiac surgery Known congenital heart disease (other than patent ductus arteriosus or Atrial septal defect) Stenotic valvular disease or left main coronary artery stenosis History of myo/pericarditis Left ventricle systolic dysfunction Cardiovascular instability/uncontro lled hypertension (h/o hypertensive urgency or emergency) History of sinus node dysfunction or high-grade AV nodal block History of aborted sudden cardiac death or cardiac arrest Current seizure disorder on AED Pregnant/Breast- feeding Any medical or social reason, which, in the opinion of the principal investigators would make the participation of the subject ill-advised.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stratum A<br>Sickle Cell patients with diastolic dysfunction | Drug: [13N]NH3<br>* Ammonia N 13 (a radioactive tracer) will be given per intravenous (IV) injection for diagnostic purposes in conjunction with positron emission tomography (PET) imaging.<br>* Other names: CAS# 34819-78-8;Drug: Lexiscan<br>* Given IV prior to PET stress test<br>* Other names: Regadenoson;Diagnostic Test: Positron emission tomography<br>* Participants will complete a onetime PET (stress-rest) myocardial perfusion scan.<br>* Other names: PET;|
| Experimental: Stratum B<br>Sickle cell patients without diastolic dysfunction | Drug: [13N]NH3<br>* Ammonia N 13 (a radioactive tracer) will be given per intravenous (IV) injection for diagnostic purposes in conjunction with positron emission tomography (PET) imaging.<br>* Other names: CAS# 34819-78-8;Drug: Lexiscan<br>* Given IV prior to PET stress test<br>* Other names: Regadenoson;Diagnostic Test: Positron emission tomography<br>* Participants will complete a onetime PET (stress-rest) myocardial perfusion scan.<br>* Other names: PET;|
| Experimental: Stratum C<br>Healthy controls | Drug: [13N]NH3<br>* Ammonia N 13 (a radioactive tracer) will be given per intravenous (IV) injection for diagnostic purposes in conjunction with positron emission tomography (PET) imaging.<br>* Other names: CAS# 34819-78-8;Drug: Lexiscan<br>* Given IV prior to PET stress test<br>* Other names: Regadenoson;Diagnostic Test: Positron emission tomography<br>* Participants will complete a onetime PET (stress-rest) myocardial perfusion scan.<br>* Other names: PET;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean and standard deviation of coronary flow reserve (CFR) | We will estimate the mean and standard deviation of CFR, as measured by PET myocardial blood flow reserve imaging, in young adult SCD patients with and without diastolic dysfunction and healthy controls. | Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour) | 
| CFR difference among Stratum A, Stratum B, and Stratum C | We will compare whether the CFR is different among 3 predefined strata: Stratum A; SCD with diastolic dysfunction patients , Stratum B; SCD without dysfunction patient control, and Stratum C; normal healthy controls by one-way ANOVA or Kruskal-Wallis one-way analysis of variance, depending on the distribution of the data. If the difference exists, the pairwise comparison will be carried out by two sample t test or Wilcoxon rank sum test between two strata. | Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between decreased CFR (quantified with PET stress-rest myocardial perfusion imaging) and presence of abnormal diastolic parameters | The following is the grouping of diastolic parameters used in this study: Group 1: 0 or any 1 diastolic variable abnormal; Group 2: Any 2 variables abnormal; Group 3: Any 3 or more variables abnormal . We will first summarize the mean and standard deviation CFR values for each diastolic group. One-way ANOVA or Kruskal-Wallis one-way ANOVA will be used to explore whether there are any statistically significant differences between the means of these three groups. If a difference exists, the pairwise comparison will be carried out by two sample t test or Wilcoxon rank sum test between two groups. | Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sickle Cell Disease patients, Healthy controls, Abnormal diastolic heart function, Coronary Flow Reserve (CFR), Coronary microvasculature dysfunction, Myocardial perfusion reserve, Positron emission tomography (PET) imaging, PET (stress-rest) myocardial perfusion imaging