People infected with HIV are more than twice as likely to die from sudden cardiac death (SCD) as the general population, and are more likely to have hearts compromised by fibrosis, a factor that can play a role. role in increasing their susceptibility to SCD, according to new findings from a UC San Francisco study.
In addition, the study found that one-third of sudden deaths initially attributed to heart causes among the HIV-positive population were instead the result of drug overdoses for which there was no apparent evidence of drug use at the scene.
The results, published on June 17, 2021, in the New England Journal of Medicine (NEJM) are the latest from the Postmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) study, in which sudden unexpected deaths in San Francisco were examined from 2011 to 2016.
POST SCD is the result of Zian H. Tseng, MD, MAS, cardiac electrophysiologist and professor in the department of medicine at UCSF. Tseng’s primary research interest is to uncover genetic, molecular, or other risk factors for sudden cardiac death – a leading cause of death from heart disease – that can be used to predict who might be most likely to benefit. preventive interventions, such as implantation of a cardiac defibrillator.
For the current study, Tseng and his team integrated a comprehensive review of medical records and EMS with a full autopsy, including histology and toxicology, with the goal of uncovering the true underlying causes of sudden death in the context of HIV.
âWe have found that the sudden death rate is more than twice as high among people living with HIV,â said Tseng, lead author of the new study. “If you focus on sudden death caused by cardiac arrhythmias, the rate in this study was 87% higher.”
Question the presumed causes of death
Sudden cardiac death occurs when the electrical signaling in the heart suddenly goes wrong and the heart stops pumping blood. Risk factors include coronary artery disease, heart attack, and previously diagnosed arrhythmias, but SCD often kills people without previously identified risks.
Tseng first considered POST SCD when he identified the need to more precisely identify cases of sudden cardiac death, after the results of his retrospective study of a potential risk factor gene in survivors of documented cardiac arrest did not agree with a well-known earlier study. in which sudden cardiac death has not been well studied.
Cardiac arrest is usually an assessment performed by emergency medical personnel at the scene. Sickle cell disease is traditionally defined by World Health Organization (WHO) criteria, in which the cardiac cause can be presumed if death occurred within an hour of symptoms, or if the deceased was seen alive without symptoms within the previous 24 hours.
âAlmost all of these deaths outside the hospital are never investigated, so it often comes down to guessing whether a sudden death was in fact due to cardiac causes,â Tseng said. “In my opinion, as researchers, we have not made any progress in finding risk factors for sudden cardiac death, because we have previously mixed many non-cardiac conditions in studies in which SCD has been presumed. “
Uniquely, POST SCD has relied on autopsies and blood tests as a kind of gold standard for assessing deaths. Every sudden death outside the hospital must be reported to the medical examiner, but in most jurisdictions autopsies have become increasingly rare, except in the case of a criminal investigation. Tseng initiated the study in conjunction with Ellen Moffatt, MD, medical examiner and deputy medical examiner for the San Francisco City and County Chief Medical Examiner’s Office, and Clinical Associate Professor in the Department of Pathology and Medicine. laboratory of the UCSF. . Moffatt autopsied each individual whose death was originally classified as sudden cardiac death.
Half of sudden deaths from other causes
While heart disease is the leading cause of death in the United States, much of which is due to sickle cell disease, results from Tseng’s studies three years ago showed that about half of sudden deaths attributed to heart disease was actually due to other causes.
âIt was a paradigm shifting discovery that continues to grow in the field of cardiology. We cannot progress in the study and prevention of sickle cell disease unless we know which cases are really cardiac. Tseng said. In addition to drug overdoses, the actual causes of death initially attributed to heart disease included pulmonary embolism, stroke, infection, diabetic ketoacidosis, gastrointestinal bleeding, renal failure, seizures and ruptured aneurysm.
In the early days of POST SCD, Tseng noticed that a disproportionate number of deaths classified as sudden cardiac deaths occurred in the HIV population. He contacted a colleague from UCSF Priscilla Hsue, MD, head of the cardiology division at Zuckerberg San Francisco General Hospital and Trauma Center, and a leading specialist in heart disease in people with HIV infection, and together they decided to further investigate sickle cell disease in people living with HIV. In their initial analysis, published in 2012, they reported that SCD rates were more than four times higher in people living with HIV, but in this study, SCDs were assumed by convention and did not require confirmation. ‘autopsy.
In the follow-up analysis now published in the NEJM, scientists at UCSF reported that suspected MSC in both HIV-positive and HIV-negative populations occurred at a rate of 53.3 versus 23.7 events per 100,000 people. -years, respectively.
There have been 610 unexpected deaths among the HIV-positive population, including 109 deaths resulting from cardiac arrest outside the hospital. A review of medical and paramedical records, forensic examination and autopsy of all but one of the 109 cases revealed multiple underlying causes of death. Of these, 48 met the criteria for a suspected SCD, but only 22 of these sudden deaths were caused by arrhythmia, with associated coronary artery disease, damaged or enlarged heart chambers, or pre-existing arrhythmic disease.
Drug overdoses detected by postmortem toxicology accounted for 16 deaths among HIV-positive people – 34 percent of the suspected SCD group. In comparison, among those who were HIV negative, overdoses accounted for 13 percent of the 505 deaths initially classified as SCD. Other causes of non-arrhythmic death in HIV-positive people with suspected CSD included kidney failure, infection, hemorrhage, and diabetic ketoacidosis.
Fibrosis in the heart
Hsue, who is the lead author of the study, said it is now clear that chronic inflammation in people infected with HIV persists even in an HIV disease that is effectively treated and suppressed. In turn, this continued inflammation is strongly predictive of clinical events, including overall mortality and cardiovascular events, kidney disease, and neurological disease. It is now known that people infected with HIV have significantly higher rates of acute myocardial infarction, heart failure, peripheral arterial disease and ischemic stroke compared to the general population.
The researchers also measured higher levels of interstitial fibrosis – in which collagen is deposited around clumps of heart cells – in the heart tissue of people with HIV. Similar fibrosis in the lymph nodes, liver and kidneys has been observed in previous studies with HIV.
âI guess this fibrosis probably represents a systemic impact of chronic HIV infection,â Hsue said. âOur evidence from this study also suggests that there were even higher levels of interstitial fibrosis among the subset of HIV-infected individuals with sudden cardiac death, and also among those whose autopsy confirmed a sudden death due to arrhythmias. In the future, it will be essential to extend this discovery by identifying those at risk with the aim of preventing sudden death in people living with HIV. In addition, therapeutic strategies aimed at reducing fibrosis will be an important area of ââinvestigation in the future. For me, this represents a truly unique study that highlights the multidisciplinary collaborations at UCSF. “
Additional UCSF co-authors are Anthony Kim, Eric Vittinghoff, Phil Ursell, Andrew Connolly, Jeffrey E. Olgin, and Joseph K. Wong. The study was funded by National Heart Lung and Blood Institute grants R01HL114822 and R01HL134182.
The University of California at San Francisco (UCSF) focuses exclusively on the health sciences and is dedicated to promoting health around the world through advanced biomedical research, higher education in the sciences of life and health professions and excellence in patient care. UCSF Health, which is the main academic medical center of UCSF, includes top-ranked specialist hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno.