HIV Infection Is Associated With Variability in Ventricular Repolarization

Abstract

Background: People living with human immunodeficiency virus (HIV+) have greater risk for sudden arrhythmic death than HIV-uninfected (HIV–) individuals. HIV-associated abnormal cardiac repolarization may contribute to this risk. We investigated whether HIV serostatus is associated with ventricular repolarization lability by using the QT variability index (QTVI), defined as a log measure of QT-interval variance indexed to heart rate variance. Methods: We studied 1123 men (589 HIV+ and 534 HIV–) from MACS (Multicenter AIDS Cohort Study), using the ZioXT ambulatory electrocardiography patch. Beat-to-beat analysis of up to 4 full days of electrocardiographic data per participant was performed using an automated algorithm (median analyzed duration [quartile 1–quartile 3]: 78.3 [66.3–83.0] hours/person). QTVI was modeled using linear mixed-effects models adjusted for demographics, cardiac risk factors, and HIV-related and inflammatory biomarkers. Results: Mean (SD) age was 60.1 (11.9) years among HIV– and 54.2 (11.2) years among HIV+ participants ( P <0.001), 83% of whom had undetectable (<20 copies/mL) HIV-1 viral load (VL). In comparison with HIV– men, HIV+ men had higher QTVI (adjusted difference of +0.077 [95% CI, +0.032 to +0.123]). The magnitude of this association depended on the degree of viremia, such that in HIV+ men with undetectable VL, adjusted QTVI was +0.064 (95% CI, +0.017 to +0.111) higher than in HIV– men, whereas, in HIV+ men with detectable VL, adjusted QTVI was higher by +0.150 (95% CI, 0.072–0.228) than in HIV– referents. Analysis of QTVI subcomponents showed that HIV+ men had: (1) lower heart rate variability irrespective of VL status, and (2) higher QT variability if they had detectable, but not with undetectable, VL, in comparison with HIV– men. Higher levels of C-reactive protein, interleukin-6, intercellular adhesion molecule-1, soluble tumor necrosis factor receptor 2, and soluble cluster of differentiation-163 (borderline), were associated with higher QTVI and partially attenuated the association with HIV serostatus. Conclusions: HIV+ men have greater beat-to-beat variability in QT interval (QTVI) than HIV– men, especially in the setting of HIV viremia and heightened inflammation. Among HIV+ men, higher QTVI suggests ventricular repolarization lability, which can increase susceptibility to arrhythmias, whereas lower heart rate variability signals a component of autonomic dysfunction.

Heart Rate Influence on the QT Variability Risk Factors

“…These observations have clear implications for further utility and research of QTVi. Many studies have repeatedly shown the risk-prediction capability of QTVi [ 32 , 33 , 34 , 35 , 36 ]. Nevertheless, both increased heart rate [ 37 , 38 ] and decreased heart rate variability [ 39 , 40 ] are well recognised strong risk factors.…”

Sudden cardiac death in HIV‐infected patients: A contemporary review

“…For example, in an HIV transgenic mice model, a significant reduction in outward K+ currents was noted along with significantly prolonged QT interval compared to the wildtype uninfected control mice in the absence of any drug therapy 17 . Heravi et al demonstrated in a cohort of 589 HIV‐infected individuals and 534 uninfected controls that HIV‐infected individuals had a higher QT interval variability, which is a marker of repolarization lability and has been found in other cohort studies to be predictive of SCD and ventricular arrhythmias 18‐20 …”

HIV-1 Tat: Role in Bystander Toxicity

“…Since HIV-infection is now a chronic disease, several comorbidities like atherosclerosis and cardiovascular disease all related to aging have become common within the population of people with HIV (Gebo et al, 2010;Clifford and Ances, 2013;Fields et al, 2013;Buggey et al, 2019;Ciccarelli et al, 2019). It is known that HIV-infected individuals have 1.5-2 times higher risk of cardiovascular disease (CVD) due to several factors like chronic inflammation, dyslipidemia, lipid abnormalities like low high-density lipoproteins (HDL), increased triglycerides, and prolonged use of ART (Wang et al, 2015;Zungsontiporn et al, 2016;Prevedel et al, 2017;Ciccarelli et al, 2019;Estrada et al, 2019;Heravi et al, 2019;Palma Reis, 2019). HIV-associated CVD is characterized by extensive loss of cardiomyocytes, increase in fibrous tissues and significant infiltration of immune cells to the heart (Prevedel et al, 2017).…”

“…A study of a multicenter AIDS cohort study (MACS) showed that there was a significant reduction in LDL and HDL from HIV-infected individuals. Commencement of ART in these individuals led to a significant increase in total cholesterol and LDL to preinfection levels while HDL remained low (Heravi et al, 2019). Interestingly, the strategies for management of antiretroviral therapy (SMART) study that examined the effect of continuous HIV-replication on CVD events showed that continuous HIV replication in individuals that discontinued therapy increased the risk of CVD compared to individuals that adhered to their therapy, clearly showing the effect of HIV replication on CVD (Siwamogsatham et al, 2019).…”