DISCUSSION
In this analysis of HIV-related hospitalizations from 2005 through 2014, we report an increase in the frequency of arrhythmias over time. The presence of arrhythmia is associated with adverse outcomes, including a higher rate of in-hospital mortality. In the current study, we report a 108% overall increase in the frequency of arrhythmia among HIV patients during the study period. To the best of our knowledge, this is the first study describing the temporal trends of arrhythmias in hospitalized HIV patients over time. Variables independently associated with the presence of arrhythmia in HIV-related hospitalizations include male sex, older age, higher income, later year of admission and the presence of comorbidities such as congestive heart failure, obesity, coronary artery disease (CAD), renal failure, hypertension, chronic pulmonary disease, history of previous myocardial infarction and peripheral vascular disease. It is notable that the frequency of these comorbidities has also increased over time, which could be contributing to the rise in overall frequency of arrhythmias during the study period. Although the association between all-cause in-hospital mortality and arrhythmia was significant, the mortality rate among patients with any arrhythmia declined over the time. The contributory factors to this decrease are unclear, but could relate to improved diagnosis and management of cardiovascular disease. This trend was consistent with the decrement in all-cause mortality found in HIV patients in general, as reported by multiple studies worldwide22-24.
In our analysis, AF has emerged as the most frequent arrhythmia among hospitalized HIV patients. Our reported frequency of AF was 2.11%. This is concordant with a previous analysis of the Veterans Affairs HIV Clinical Case Registry, which reported a frequency of 2.6% of atrial fibrillation in a large cohort of over 30,000 HIV patients from 1996 to 201110.
While our study does not address the mechanisms underlying the significant frequency of arrhythmias in the setting of HIV, other studies may provide insight. HIV infection is known to be an important risk factor for atherosclerosis and stroke25, 26, and similar mechanisms can explain the incidence of arrhythmias in that population. Both advanced age and inflammation have been associated with an increased risk for developing arrhythmias such as AF27, 28, making older patients with chronic HIV particularly susceptible to developing it. Indeed, persistent immunodeficiency, accelerated immunosenescence and inflammation in HIV patients were found to accelerate the onset of age-associated diseases, including cardiovascular diseases and arrhythmias such as AF29. Elution of inflammatory cytokines and reactive oxygen species by infected cardiac endothelium; expression of HIV-associated proteins that lead to destruction of mitochondria and myocardial damage, are mechanisms previously implicated in the pathogenesis of AF in HIV infected patients30. The severity of the HIV infection also correlates with the risk of developing AF. A previous analysis identified low CD4+ cell count and high HIV RNA viral load as independent variables for the development of AF in HIV patients10. However, the exact mechanism underlying this correlation is difficult to establish given that many patients in the HIV population share similar risk factors for AF, such as hypertension, CAD and heart failure, as evidenced by our study. Additionally, components of highly active antiretroviral therapy (HAART) such as protease inhibitors are associated with development of metabolic syndrome, which is a risk factor for AF31.
In our study, the frequency of malignant arrhythmias such as VF and VT has increased over the years. While the reason behind this rise is unclear, previous studies showed that patients with HIV can have a prolonged QTc, predisposing them to malignant arrhythmias including torsades de pointes, sustained VT and VF. This prolongation can be a direct result of the HIV infection itself, and can be observed in the absence of overt cardiovascular disease 7, 32. The severity of the HIV infection, evidenced by a low CD4+ cell count and high viral load, has been shown to be a risk factor for the development sudden cardiac death (SCD) 11. Furthermore, medications frequently administered to HIV patients, including pentamidine, TMP-SMX (Trimethoprime-Sulfamethoxazole), non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva), and protease inhibitors such as atazanavir (Reyataz)33, have also been associated with QTc prolongation7, 34, 35. It is possible that the increasingly widespread use of such medications contributed to the rise of malignant arrhythmias in the HIV population over the study years. Furthermore, the increased frequency of cardiovascular conditions such as CAD and CHF in the HIV population, as shown by our study, have likely contributed to the rise of such arrhythmias. These findings call for increased scrutiny to the QTc interval in HIV patients, and warrant considering HIV disease status in the risk assessment of malignant arrhythmias .