Increased Sudden Cardiac Death, Myocardial Fibrosis Seen in Persons Living With HIV

Compared with individuals without known HIV infection, persons living with HIV had higher rates of sudden cardiac death and increased interstitial myocardial fibrosis in a new New England Journal of Medicine study.

Persons living with HIV were shown to have higher rates of presumed sudden cardiac death and increased levels of interstitial myocardial fibrosis compared with persons without known HIV infection, according to a new New England Journal of Medicine study.

Additionally, occult drug overdose was most often the root cause of presumed sudden cardiac deaths in individuals living with HIV compared with those not living with HIV, at 34% vs 13%, respectively.

“We found that the rate of sudden death is more than twice as high among persons living with HIV," Zian H. Tseng, MD, MAS, cardiac electrophysiologist; professor in the Department of Medicine at the University of California, San Francisco; and lead author of the HIV POST SCD study, said in a statement. “If you narrow the focus to sudden death caused by heart arrhythmias, the rate in this study was 87% higher.”

These findings from the HIV POST SCD study, by investigators at Zuckerberg San Francisco General Hospital and the Office of the Chief Medical Examiner, City and County of San Francisco, build on previous data from the researchers’ POST SCD study. In that study, they used medical examiner data to describe the rate and “cause of all deaths due to out-of-hospital cardiac arrest and deaths presumed to be sudden cardiac deaths (as defined by the World Health Organization) in San Francisco County.”

To be included in the study analysis, the team looked at all deaths among persons aged 18 to 90 years living with HIV due to out-of-hospital cardiac arrest in San Francisco County between February 1, 2011, and September 21, 2016. Their data came from all reported related to an out-of-hospital cardiac arrest (eg, premortem medical records, postmortem findings, EMS records), while a complete external and internal postmortem examination was performed for all deaths due to out-of-hospital cardiac arrest, excluding those for which the family did not provide consent.”

This amounted to 48 presumed sudden cardiac deaths among the target patient population, which equated to 54.5 per 100,000 person-years across the county or 3.5% of all deaths among person living with HIV in San Francisco County. There was an overall 1379 deaths, with 610 unexpected deaths reported to the medical examiner, 109 of which were attributed to out-of-hospital cardiac arrest. Ninety-nine percent of the families (n = 47) consented to autopsy.

Among the 47 presumed sudden cardiac deaths with autopsy data, the mean (SD) age was 54.57 (10.27) years, 94% were male, 77% were White, 19% were Black, and 4% were Hispanic. The reference group (n = 505) was slightly older, at 63.04 (14.48) years; 68% were male; and most were White (53%), Asian (22%), or Black (15%).

Occult drug overdose from methamphetamines, alcohol, and opiates was the most common cause of presumed sudden cardiac death among the HIV cohort, happening in one-third of all cases. This finding was in contrast to the initial EMS personnel impression of cardiac arrest.

Drilling down to specific types of sudden cardiac death, arrhythmia occurred at similar levels in the cohort with HIV vs those without known HIV infection, at 47% and 56%, respectively, followed by chronic coronary artery disease (19% and 22%) and cardiomyopathy (11% and 10%).

Additional information on incidence rates include the following:

  • More than 2-fold higher observed incidence rate per 100,000 person-years of presumed sudden cardiac death in the HIV-positive cohort vs the reference group: 53.3 vs 23.7 (incidence rate ratio [IRR], 2.25; 95% CI, 1.37-3.70)
  • Close to a 2-fold higher incidence rate per 100,000 person-years of sudden death from arrhythmia in the HIV cohort: 25.0 vs 13.3 (IRR, 1.87; 95% CI, 0.93-3.78)
  • Elevated incidence rate of presumed sudden cardiac death in women living with HIV vs women in the reference group (IRR, 3.93; 95% CI, 1.07-14.44)
  • Elevated incidence rate of presumed sudden cardiac death among White individuals living with HIV vs White persons in the reference group (IRR, 2.29; 95% CI, 1.12-4.69)

Psychiatric diagnoses were also significantly more likely in the HIV cohort, at 57% compared with 27% in the reference group.

When degree of fibrosis was investigated for its possible contribution to sudden cardiac death, total fibrosis, interstitial and perivascular fibrosis, and replacement fibrosis—expressed as mean (SD) percent fibrosis—were all elevated in the HIV-positive group compared with the reference group:

  • Total fibrosis: 12.5 (6.4) vs 8.7 (7.5)
  • Interstitial and perivascular fibrosis: 10.9 (5.4) vs 7.7 (6.5)
  • Replacement fibrosis: 1.6 (2.8) vs 1.0 (1.9)

The authors explained that following postmortem investigation, results from previous studies on sudden cardiac death without autopsy have been overturned, in that among deaths deemed cardiac related—regardless of HIV status—50% were actually noncardiac related.

“Our study shows the importance of rigorous phenotyping of sudden cardiac death to establish the underlying mechanism,” the authors wrote, adding that their results on drug overdose “highlights the role of noncardiac causes of sudden death in this context.”


Tseng ZH, Moffatt E, Kim A, et al. Sudden cardiac death and myocardial fibrosis, determined by autopsy, in persons with HIV. N Engl J Med. Published online June 16, 2021. doi:10.1056/NEJMoa1914279

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