Sudden cardiac death (SCD) is one of the leading causes of mortality in the general population, accounting for 5-15% of total deaths in the United States and other industrialized countries.1,2 With the advent of antiretroviral therapy, HIV-infected individuals now are faced with health issues related to aging, including cardiovascular disease. Individuals with HIV have higher rates of coronary events compared to controls and a growing body of literature from our group and others demonstrates that they are at increased risk for developing accelerated atherosclerosis.3,4 Emerging studies suggest that HIV-related inflammation is independently associated with premature coronary artery disease.5,6 In addition, other cardiovascular abnormalities have been described in the setting of HIV infection including cardiomyopathy,7 pulmonary hypertension8 and a prolonged QT interval,9,10 all of which make SCD an important health concern in this patient population. Our group has recently shown that SCD accounts for the largest proportion of non-AIDS deaths among HIV-infected individuals, at a rate that is over four-fold higher than the background population. While the exact mechanisms behind SCD in this population are unknown, malignant arrhythmias likely play a strong role. Prior myocardial infarction and structural heart disease are major risk factors for malignant arrhythmias in the general population, but the rates and risk factors for ventricular arrhythmias and SCD in the setting of HIV infection are unknown. HIV-specific factors such as chronic inflammation,19 antiretroviral use,4, 9 or direct viral effect on cardiomyocyte repolarization 22, 3 may interact with the arrhythmogenic substrate of cardiovascular disease (CVD) to substantially increase the risk of arrhythmia. We hypothesize that HIV-infected patients with CVD will have higher rates of ventricular arrhythmias compared to matched HIV-negative controls with similar heart disease. To address this hypothesis, we will evaluate pathologic electrocardiographic (ECG) parameters and ventricular arrhythmias in cardiac patients with and without HIV using 48-hour ambulatory Holter monitoring and 12-lead ECGs. Additionally, we will evaluate the association of inflammatory markers and HIV-related factors with SCD in a large outpatient cohort of HIV-infected individuals. This study will form the basis for future investigations that wll assess whether certain interventions, either HIV-related or cardiovascular, are successful in reduction of SCD in the setting of HIV infection.

Public Health Relevance

With current antiretroviral medical therapies, HIV-infected individuals are now living longer and are increasingly likely to suffer from non-AIDS related illnesses, including high rates of coronary artery disease and heart failure. We have recently shown that HIV-infected individuals have a high incidence of sudden cardiac death (SCD), a condition typically caused by malignant ventricular arrhythmias. The burden of ventricular arrhythmias and risk factors for SCD in HIV-infected patients is currently unknown, and we plan to evaluate these in this proposal to help determine which individuals are at high risk for this lethal disease.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL114425-02
Application #
8655797
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wang, Wayne C
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Moyers, Brian S; Secemsky, Eric A; Vittinghoff, Eric et al. (2014) Effect of left ventricular dysfunction and viral load on risk of sudden cardiac death in patients with human immunodeficiency virus. Am J Cardiol 113:1260-5