Diastolic Dysfunction in Patients with Human Immunodeficiency Virus Receiving Antiretroviral Therapy: Results from the CHART Study.

Abstract

BACKGROUND\nDiastolic dysfunction (DD) is common and occurs at an earlier age among human immunodeficiency virus -infected (HIV+) individuals, but the mechanisms and consequences of DD among HIV+ individuals are unclear.\n\n\nMETHODS AND RESULTS\nThe Characterization of Heart Function on Antiretroviral Therapy (CHART) study was a multi-center cross-sectional case-control study of treated and virally suppressed HIV+ individuals with (DD+) and without DD (DD-). All patients had normal ejection fraction (>50%), no significant valvular disease, and no history of coronary revascularization or persistent atrial fibrillation. Overall, 94 DD+ and 101 DD- patients were included. DD+ patients were older with higher body mass index and more likely to have hypertension, renal dysfunction, and dyslipidemia. Groups were similar with respect to sex, race, CD4 count, and HIV RNA copies. NT-pro-B-type natriuretic peptide levels (median 36 [23, 85] vs. 26 [12, 49] pg/mL, p<0.01) and high-sensitivity troponin I (3.6 [2.6, 5.1] vs. 2.5 [1.8, 3.5] pg/mL, p<0.01) were higher among DD+ patients. The latter had similar left atrial size, but increased stiffness (conduit strain, 23.5 [17.5, 36.9] vs. 30.0 [22.9, 37.0], p<0.01) and impaired relaxation (reservoir strain, 39.7 [32.0, 58.0] vs. 45.9 [37.0, 60.6], p=0.04). On CMR, the prevalence of focal fibrosis was higher among DD+ patients (19.0% vs. 5.3%, p<0.01). DD+ patients demonstrated higher levels of carboxyl-terminal telopeptide of collagen type I (p=0.04), and trends towards higher IL-6 and oxidized low-density lipoprotein levels (p≤0.08). KCCQ physical limitation (87.1±21.4 vs. 93.1±18.1, p=0.01) and symptom frequency scores were lower among DD+ patients (86.0±21.5 vs. 92.5±16.8, p=0.01).\n\n\nCONCLUSIONS\nIn this contemporary HIV+ population receiving antiretroviral therapy, DD was associated with multiple alterations in cardiac structure and function, including myocardial fibrosis and left atrial abnormalities, and worse quality of life. Further studies are needed to assess longitudinal changes in these parameters and their potential as therapeutic targets to prevent progressive cardiac remodeling and dysfunction in HIV.\n\n\nCLINICAL TRIAL REGISTRATION\nURL: http://www.clinicaltrials.gov. Unique identifier: NCT02860156.