The many facets of cardiopulmonary complications in sickle cell disease

Abstract

Sickle cell disease (SCD) is a systemic vasculopathy, which progressively remodels the heart and pulmonary circulation through chronic anemia, hemolysis, and endothelial dysfunction. This review integrates current evidence on the mechanisms, clinical spectrum, and management of SCD-related cardiopulmonary complications. Chronic anemia drives a high-output state characterized by cardiac chamber dilation leading to eccentric remodeling that, over time, may evolve toward diastolic dysfunction, heart failure with preserved ejection fraction (HFpEF), and postcapillary pulmonary hypertension (PH). Concomitant hemolysis, oxidative stress, and microvascular injury promote diffuse myocardial fibrosis that acts as an arrhythmogenic substrate underlying both atrial and ventricular arrhythmias (VAs). Beyond left-sided cardiac disease, SCD also contributes to pulmonary vascular injury and “relative systemic hypertension”, both reflecting a vasculopathy process that amplifies target organs damage. Transthoracic echocardiography (TTE) remains the cornerstone of diagnosis and prognosis of SCD-related cardiomyopathy, enabling longitudinal assessment of ventricular performance, chamber remodeling and hemodynamics including pulmonary pressures, while cardiac magnetic resonance (CMR) adds information on tissue characterization and quantification of diffuse fibrosis. Emerging data suggests that curative therapies. Such as hematopoietic stem cell transplantation and gene therapy can reverse cardiac remodeling and fibrosis yet necessitate structured long-term follow-up. Recognizing SCD-related cardiomyopathy as a dynamic and potentially reversible cardiopulmonary continuum is essential for establishing disease-specific diagnostic criteria and guiding physiological grounded therapeutic strategies.