The Pattern of Cardiac Remodeling in Pediatric and Adolescent Patients with Sickle Cell Disease and the Association with the Genotype and the Clinical Severity of the Disease: A Systematic Review

Background: Sickle cell disease (SCD) is the most common inherited blood disorder globally, affecting approximately 300,000 newborns annually. Cardiac remodeling, resulting from chronic anemia, vascular obstruction, and endothelial dysfunction, substantially contributes to morbidity and mortality in SCD. Apprehending these patterns is important for guiding clinical management and enhancing outcomes in pediatric patients. However, a comprehensive summary of cardiac remodeling patterns in pediatric and adolescent SCD, and their associations with genotype and clinical severity, is lacking. Methods: We conducted a systematic review following PRISMA 2020 guidelines, searching five databases for studies published from January 1978 to December 2024. Of 1,131 records, 37 studies met the inclusion criteria: 31 focused exclusively on children (Group A), and 6 included both children and adults (Group B). We analyzed cardiac remodeling patterns, genotype-specific findings, associations with disease severity, and imaging modalities. The 37 studies included approximately 4,847 patients from 18 countries, covering varied populations and imaging techniques. Left ventricular (LV) dilation was the most frequent finding (89.2%), followed by diastolic dysfunction (48.6%), pulmonary hypertension or elevated tricuspid regurgitant jet velocity (TRV; 37.8%), myocardial fibrosis (8.1%), and arrhythmia (2.7%). The HbSS genotype was associated with the most severe cardiac changes. Markers of disease severity, such as elevated lactate dehydrogenase (LDH), frequent acute chest syndrome (ACS), and increased hospitalizations, were strongly correlated with more pronounced cardiac remodeling. Variability in study design and imaging modalities underscores the requirement for standardized assessment protocols to enhance comparability and clinical translation. Cardiac remodeling in SCD starts early, even in infancy, and progresses with age. Recognizing this early can prompt healthcare professionals to prioritize rapid interventions and point out the importance of early monitoring and management.