A new phase 2, nonrandomized clinical trial will investigate decreased blood flow to the heart during stress as a potential cause of heart damage in patients with sickle cell disease (SCD).

The study will include 3 arms: SCD with diastolic dysfunction (stratum A), SCD without diastolic dysfunction (stratum B), and healthy controls (stratum C). Participants (estimated enrollment, 40) will be given intravenous (IV) ammonia N 13, a radiopharmaceutical for diagnostic positron emission tomography (PET), and IV lexiscan, a pharmacologic stress agent.

The trial requires 2 visits. In the first visit, participants will do blood tests, an electrocardiogram, and an echocardiogram, whereas in the second visit, participants will complete a onetime PET (stress-rest) myocardial perfusion scan.

Primary outcome measures of the trial include mean and standard deviation of coronary flow reserve (CFR) and CFR differences among study arms. In addition, investigators will assess the relationship between decreased CFR and the presence of abnormal diastolic parameters.

Read more about SCD guidelines and recommendations

Participants must be black adults aged between 18 and 21 years. Additional inclusion criteria include a diagnosis of SCD (homozygous HbSS and sickle β-thalassemia genotypes) for stratum A and stratum B, 3 or more abnormal diastolic parameters (American Society of Echocardiography guidelines) for stratum A, and 2 or less abnormal diastolic parameters for stratum B and stratum C.

Patients who were recently hospitalized due to vaso-occlusive pain crisis or acute chest syndrome, received blood transfusion in the last 3 months, had a previous cardiac surgery, or show signs, symptoms, or electrocardiogram findings of acute myocardial ischemia, infarction, or unstable angina are excluded from the trial.

Also excluded are participants with congenital heart disease (exceptions applied for patent ductus arteriosus or atrial septal defect), stenotic valvular disease or left main coronary artery stenosis, left ventricle systolic dysfunction, cardiovascular instability/uncontrolled hypertension, and current seizure disorder on antiepileptic drugs, as well as those with history of ventricular or superventricular tachycardia or ventricular fibrillation, myo/pericarditis, sinus node dysfunction or high grade atrioventricular nodal block, and aborted sudden cardiac death or cardiac arrest.

The study will not include pregnant or breastfeeding women.


Relationship between abnormal myocardial perfusion and diastolic dysfunction in sickle cell disease using PET. ClinicalTrials.gov. October 18, 2022. Updated November 10, 2022. Accessed November 17, 2022.