Associations between QT interval subcomponents, HIV serostatus, and inflammation

Abstract

Background The total QT interval comprises both ventricular depolarization and repolarization currents. Understanding how HIV serostatus and other risk factors influence specific QT interval subcomponents could improve our mechanistic understanding of arrhythmias. Methods Twelve‐lead electrocardiograms (ECGs) were acquired in 774 HIV‐infected (HIV+) and 652 HIV‐uninfected (HIV−) men from the Multicenter AIDS Cohort Study. Individual QT subcomponent intervals were analyzed: R‐onset to R‐peak, R‐peak to R‐end, JT segment, T‐onset to T‐peak, and T‐peak to T‐end. Using multivariable linear regressions, we investigated associations between HIV serostatus and covariates, including serum concentrations of inflammatory biomarkers such as interleukin‐6 (IL‐6), and each QT subcomponent. Results After adjustment for demographics and risk factors, HIV+ versus HIV− men differed only in repolarization phase durations with longer T‐onset to T‐peak by 2.3 ms (95% CI 0–4.5, p < .05) and T‐peak to T‐end by 1.6 ms (95% CI 0.3–2.9, p < .05). Adjusting for inflammation attenuated the strength and significance of the relationship between HIV serostatus and repolarization. The highest tertile of IL‐6 was associated with a 7.3 ms (95% CI 3.2–11.5, p < .01) longer T‐onset to T‐peak. Age, race, body mass index, alcohol use, and left ventricular hypertrophy were each associated with up to 2.2–12.5 ms longer T‐wave subcomponents. Conclusions HIV seropositivity, in combination with additional risk factors including increased systemic inflammation, is associated with longer T‐wave subcomponents. These findings could suggest mechanisms by which the ventricular repolarization phase is lengthened and thereby contribute to increased arrhythmic risk in men living with HIV.

Testosterone use and shorter electrocardiographic QT interval duration in men living with and without HIV

“…Notably, in the present analysis, the absolute change in QTc associated with T‐use was larger than that associated with HIV seropositivity. Given the association of longer QTc with HIV infection and the increased prevalence of hypogonadism and low T‐levels in MLWH [4–5,14], the shorter QTc associated with T‐use observed in this study might support a protective effect on ventricular repolarization that could counteract the potentially deleterious prolongation seen with HIV infection. In light of our findings, QTc duration data may be helpful when evaluating initiation and discontinuation of T‐use, particularly in MLWH without cardiovascular disease and those taking QTc‐prolonging medications.…”

“…Our findings demonstrate that T‐use is associated with shorter electrocardiographic QTc duration independent of HIV serostatus. This finding may be particularly relevant for MLWH, as MLWH are less likely to discontinue testosterone and more likely to have QT prolongation associated with HIV infection [5,16]. Longer QTc duration has been associated with HIV infection.…”

“…We included data from participants who, as part of the MACS study, underwent standard resting 12‐lead electrocardiograms in 2016–2017 and reported the presence or absence of T‐use in the 6 months preceding visits since 2012. For each participant, a standardized QT interval duration was measured digitally and corrected for heart rate using the linear Framingham formula to generate the QTc, as previously described [5]. All participants provided written informed consent, and study procedures were approved by institutional review boards at each site.…”

“…A risk factor for SCD in the general population is prolongation of the corrected QT interval (QTc), an electrocardiographic measure of ventricular repolarization [3]. We previously reported an independent association between HIV infection and longer QTc [4–5] but did not assess the influence of testosterone usage (T‐use). In the general population, low testosterone levels (T‐levels) are associated with 4–11 ms QTc prolongation [6–9], whereas high T‐levels are associated with lower SCD risk in men [10–11].…”

Management of Arrhythmias Associated with COVID-19

“…Previous studies have suggested that increase in cytokines, such as IL-6, may prolong QT in patients with viral infection. HIV-associated inflammation, causing elevated IL-6, has been shown to be independently associated with QT prolongation [ 80 ] and prolonged repolarization represented as T wave onset-to-peak duration [ 81 ]. HIV-positive patients had longer QTc intervals and QTc prolongation often > 500 ms, even after taking into account other QT prolonging drugs like methadone when compared to HIV negative patients [ 82 ].…”