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 .