Diastolic Dysfunction in Individuals with Human Immunodeficiency Virus Infection: Literature Review, Rationale and Design of the Characterizing Heart function on Anti-Retroviral Therapy (CHART) Study

Antiretroviral therapy (ART) has been associated with a shift in the epidemiology of HIV-associated cardiomyopathy from a phenotype of primarily left ventricular (LV) systolic dysfunction to LV diastolic dysfunction (DD). Patients with HIV receiving ART have higher rates of DD when compared to age-matched controls and develop DD at a younger age. However, little is known about the natural history and pathogenesis of DD in virally suppressed HIV-infected patients. Current evidence suggests that immune processes modulate the risk for cardiac involvement in HIV-infected persons. Ongoing inflammation appears to have myocardial effects and accelerated myocardial fibrosis appears to be a key mediator of HIV-induced DD. The Characterizing Heart Function on Antiretroviral Therapy (CHART) study aims to systematically investigate determinants, mechanisms, and consequences of DD in HIV-infected patients. We will compare ART-treated, virally suppressed HIV-infected individuals with and without DD and HIV- individuals with DD in regards to (1) systemic inflammation, myocardial stress, and subclinical myocardial necrosis through circulating biomarkers; (2) immune system activation through cell surface receptors; (3) myocardial fibrosis by cardiac magnetic resonance; (4) markers of fibrosis and remodeling, oxidative stress, and hypercoagulability; (5) left atrial function through echocardiography; (6) proteomic and metabolomic profiles; and (7) phenotype signatures derived from clinical, biomarker, and imaging data.