Outcomes of implantable cardioverter-defibrillator implantation in HIV-infected patients: A single-center retrospective cohort study.

BACKGROUND: HIV-infected individuals have a known increased risk of sudden cardiac death (SCD) compared to uninfected individuals. Implantable cardioverter-defibrillators (ICDs) are standard therapy for preventing SCD; however, there is limited data on the outcomes of ICDs in HIV-infected individuals. HYPOTHESIS: HIV-infected subjects receive a higher number of appropriate ICD therapies than uninfected controls. METHODS: This is a retrospective cohort study of 35 consecutive HIV-Infected patients and 36 uninfected controls matched by age, race, and gender who were treated at the University of North Carolina Medical Center in the outpatient or inpatient setting from 2014 to the present and had undergone ICD implantation. For HIV-infected subjects, a multivariate Poisson regression analysis was performed to evaluate the association between covariates and ICD therapies. RESULTS: Among HIV-infected subjects, the mean CD4 count was 582.5 cells/mm3 and 69% had an undetectable viral load. The median follow-up was 6.4 years. HIV-infected subjects had both a higher number of appropriate ICD shocks or antitachycardia pacing (ATP) therapy per person-year as well as a higher number of inappropriate ICD shocks per person-year than uninfected controls (1.512 vs. 0.590 and 0.122 vs. 0.0166, respectively, p < .001 for both comparisons). After multivariate adjustment, the presence of detectable/unsuppressed viral load at the time of ICD implantation was an independent predictor of both of the following in HIV-infected subjects: (1) appropriate ICD discharge (p = .004), and (2) appropriate ICD discharge or appropriate ATP therapy (p < .001). CONCLUSION: HIV-infected subjects had a higher number of appropriate ICD discharge or ATP therapy per person-year than matched uninfected controls.

Sudden cardiac death in HIV-infected patients: A contemporary review.

HIV-infected individuals have an increased risk of sudden cardiac death compared to the general population; yet the mechanisms underlying this increased risk remain unclear. The mechanisms underlying the heightened sudden cardiac death risk in HIV-infected individuals is likely multifactorial. We reviewed the literature to elucidate and summarize the potential mechanisms contributing to sudden cardiac death in the HIV patient population. There is biologic plausibility that the following mechanisms may be contributing to the significantly heightened risk of sudden cardiac death in HIV to varying degrees: ventricular arrhythmias, myocardial fibrosis and scar, prolonged QTc interval (both as a direct effect of HIV on repolarization as well as a result of concurrent medications/antiretroviral therapies), substance abuse, structural heart disease, and premature atherosclerosis. Further understanding of the mechanisms underlying the increased sudden cardiac death risk in HIV can lead to identification of modifiable risk factors, implementation of public health programs, and potential revision of ICD implantation guidelines to ultimately reduce the incidence of sudden cardiac death in HIV-infected patients. Further studies are needed to assess the relative contribution of each of these mechanisms and risk factors.

A novel minimally-invasive method to sample human endothelial cells for molecular profiling.

OBJECTIVE: The endothelium is a key mediator of vascular homeostasis and cardiovascular health. Molecular research on the human endothelium may provide insight into the mechanisms underlying cardiovascular disease. Prior methodology used to isolate human endothelial cells has suffered from poor yields and contamination with other cell types. We thus sought to develop a minimally invasive technique to obtain endothelial cells derived from human subjects with higher yields and purity. METHODS: Nine healthy volunteers underwent endothelial cell harvesting from antecubital veins using guidewires. Fluorescence-activated cell sorting (FACS) was subsequently used to purify endothelial cells from contaminating cells using endothelial surface markers (CD34/CD105/CD146) with the concomitant absence of leukocyte and platelet specific markers (CD11b/CD45). Endothelial lineage in the purified cell population was confirmed by expression of endothelial specific genes and microRNA using quantitative polymerase chain reaction (PCR). RESULTS: A median of 4,212 (IQR: 2161-6583) endothelial cells were isolated from each subject. Quantitative PCR demonstrated higher expression of von Willebrand Factor (vWF, P<0.001), nitric oxide synthase 3 (NOS3, P<0.001) and vascular cell adhesion molecule 1 (VCAM-1, P<0.003) in the endothelial population compared to similarly isolated leukocytes. Similarly, the level of endothelial specific microRNA-126 was higher in the purified endothelial cells (P<0.001). CONCLUSION: This state-of-the-art technique isolates human endothelial cells for molecular analysis in higher purity and greater numbers than previously possible. This approach will expedite research on the molecular mechanisms of human cardiovascular disease, elucidating its pathophysiology and potential therapeutic targets.