Deaths caused by sudden cardiac arrest are significantly more common in people living with HIV than the general population and were more likely to be associated with overdose or kidney failure in people with HIV, as well as low CD4 count or detectable viral load, two studies presented on Tuesday at the Conference on Retroviruses and Opportunistic Infections (CROI 2019) show.
Sudden cardiac death is caused by electrical malfunction in the heart after disturbance in the heartbeat rhythm (arrhythmia). It can be treated by prompt use of a defibrillator, a machine which shocks the heart back to a normal heartbeat, and by cardiopulmonary resuscitation (CPR), which provides the heart and brain with oxygen until the heart resumes its normal activity.
The underlying cause of the arrhythmia may be coronary artery disease, a structural defect in the heart, congestive heart failure, trauma, overdose or a rare genetic disorder.
Sudden cardiac arrest causes around 325,000 deaths each year in the United States and is the most common natural cause of death in younger adults.
Several research groups have reported high rates of sudden cardiac death in people living with HIV but there has been a lack of information about the incidence or risk factors for sudden cardiac death in large cohorts.
Two American research groups presented results of studies at CROI 2019 with different methodologies that sought to define the incidence of sudden cardiac death.
Sudden cardiac deaths and sudden arrhythmia deaths
Researchers from the University of California San Francisco looked at all sudden cardiac deaths and sudden arrhythmic deaths that occurred outside a hospital setting in San Francisco County between 2011 and 2016. Autopsies were carried out in all cases of out-of-hospital cardiac arrest. Sudden arrhythmic deaths were autopsy-defined deaths where no extracardiac cause of death could be identified.
They identified 47 out-of-hospital sudden cardiac deaths in people with HIV and 505 in the HIV-negative population in the same period. Sudden cardiac deaths occurred at a significantly younger age in people with HIV (54 years vs 63 in the general population, p < 0.001) and people with HIV who suffered sudden cardiac death were more likely to have a previous history of heart attack, to have a psychiatric diagnosis, current substance, alcohol and tobacco use.
Approximately half of the deaths (47%) were sudden arrhythmic deaths. Sudden arrhythmic deaths are cases which can be rescued by use of a defibrillator.
Sudden cardiac death was more commonly due to occult overdose (an overdose where drug overdose had not been immediately apparent) in people with HIV. Just over one-third of all sudden cardiac deaths were judged to be due to occult overdose in people living with HIV, compared to 13% in HIV-negative people (p < 0.0001). Occult overdose was defined as a case where no drug use was detected at the scene of death, only upon autopsy.
Sudden cardiac death due to kidney failure was more common in people living with HIV (6% vs 1%, p = 0.003).
The incidence ratio of sudden cardiac death was approximately 86% higher in people living with HIV than HIV-negative people (1.86 for SCD, 95% CI 1.39-2.4, p < 0.0005) while the incidence of sudden arrhythmic death was 58% higher (1.58 for SAD, 95% CI 1.02-2.43, p = 0.006).
Although the incidence of sudden cardiac death and sudden arrhythmic death were each higher in black people than in other demographic groups, the incidence ratio did not differ significantly between HIV-positive and HIV-negative black people. In white people on the other hand, the incidence of sudden cardiac death was approximately twice as high (p = 0.006).
The investigators noted a significantly higher prevalence of cardiac fibrosis – abnormal thickening of the heart valves due to deposition of collagen in the myocardium – in people living with HIV who suffered a sudden cardiac death.
After controlling for age, gender, heart disease and coronary artery disease, people with HIV who suffered sudden cardiac death had 60% greater extent of interstitial fibrosis at autopsy than HIV-negative people. Fibrosis occurs with ageing and is associated with the development of heart failure.
“This might be the mechanism by which HIV increases the risk for fatal arrhythmias,” said Dr Zian Tseng of University of California San Francisco. But how fibrosis occurs is still unclear. “Is there chronic inflammation, activated immune cells circulating? I think it’s controversial if there is direct HIV infection of the myocardial cells,” he told a press conference.
Sudden cardiac death in the Veterans Aging Cohort Study
In the second study, researchers from the Veterans Aging Cohort Study looked at sudden cardiac death outside the hospital setting in 144,362 US military veterans between 2003 and 2014, of whom 43,413 had HIV. The study excluded cases of cancer, dialysis, AIDS-defining illness or CD4 count below 50 or a significant new health condition in the month preceding death, in order to focus on the risk in otherwise healthy people.
The mean age of cohort participants was 50 years and participants were followed for a median of ten years. Participants were predominantly male (97%) and African American (47%).
A total of 777 cases of sudden cardiac death were detected in people with HIV. The risk of sudden cardiac death was 15% higher in people living with HIV (HR 1.15, 95% CI 1.05-1.26).
After adjustment for age, sex, race/ethnicity, risk factors for cardiovascular disease, substance use and prevalent cardiovascular disease, the risk was elevated in people living with HIV only among those with CD4 cell counts below 200 cells/mm3 and among people with a detectable viral load (> 500 copies/ml). After adjustment for time-updated CD4 cell count and viral load, the risk was elevated in people who persistently had CD4 counts below 200 or viral loads above 500 copies/ml.
Age per 10 years, male sex, cardiovascular disease, controlled hypertension, current smoking and hepatitis C virus infection each increased the risk of sudden cardiac death. So too did higher body mass index, anaemia, alcohol use disorder and chronic pulmonary disease.
“The only way to prevent sudden cardiac death is to implant a defibrillator and there are strict criteria to qualify for a defibrillator,” said Dr Tseng. He said there is a need to study potential correlates on an MRI scan to qualify more patients who may not have a left-ventricular ejection fraction below the qualifying threshold.
Tseng ZS et al. HIV post SCD study: 80% higher rate of autopsy-defined sudden arrhythmic death in HIV. Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 33, 2019.
Freiberg M et al. Sudden cardiac death among HIV-infected and uninfected veterans. Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 32, 2019.