Cardiopulmonary complications such as pulmonary hypertension and congestive heart failure remain among the most challenging aspects to manage and are leading causes of sudden death in people living with sickle cell disease (SCD).1 Work by Omar Niss, MD, and colleagues has demonstrated that myocardial fibrosis is common in young individuals with SCD, preceding later complications such as diastolic dysfunction.2 This, in turn, likely contributes to the development of arrhythmias including ventricular tachycardia, a well-described proximate etiology of sudden death. The epidemiology of cardiac arrhythmias in people living with SCD is unknown.
In this French study, Thomas d’Humières, MD, and colleagues sought to define the prevalence of and potential risk factors for ventricular arrhythmias (VA) in a high-risk subset of individuals living with SCD. Individuals over 15 years old with SCD were eligible for inclusion if they had signs or symptoms of cardiac dysfunction such as angina, dyspnea, palpitations, heart failure, abnormal echocardiogram findings and abnormal levels of cardiac biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) or troponin. Enrolled participants were hospitalized for one day and underwent a comprehensive assessment, which included an electrocardiogram (EKG), echocardiogram, and a six-minute walk test. Additional tests such as 24-hour EKG monitoring and coronary angiography were obtained at the discretion of the treating physicians and study team. Only participants who underwent 24-hour EKG monitoring were included in the final analysis.
Of the 100 included participants, 22% had VA (68% with frequent premature ventricular contractions and 41% with non-sustained ventricular tachycardia). Additionally, atrial arrythmias were discovered in a subset of participants (3% with atrial fibrillation, 17% with premature atrial contractions). There was no evidence of coronary artery disease in the 47% of individuals who had been screened. The multivariable analysis revealed that male sex, abnormal left ventricular global longitudinal strain (GLS; an echocardiographic marker of myocardial function), and decreased platelet count were associated with increased VA. In addition to these variables and other echocardiogram markers, NT-proBNP, diastolic blood pressure, and minimum oxygen saturation during the walking test were associated with VA in the univariable analysis.
In Brief
In people living with SCD who have signs or symptoms of cardiac dysfunction, there is an unexpectedly high prevalence of ventricular arrhythmias — a known trigger for sudden death. Promising biomarkers for VA include abnormal echocardiogram findings such as GLS, which is not routinely performed but should be considered based on the preliminary findings of this study. Unresolved topics to be examined in future studies include the prevalence of VA in the overall SCD population, prognosis and risk of sudden death in individuals with SCD and VA, and whether disease-modifying therapies such as hydroxyurea or chronic transfusions can slow or prevent the progression of cardiac disease. At minimum, people living with SCD who have cardiac risk factors should be further screened for VA, and close collaboration with cardiology teams should be considered essential for managing and reducing the risk of sudden death in these patients.
Competing Interests
Dr. Wilson indicated no relevant conflicts of interest.
