One in six people diagnosed with sudden cardiac death actually died from an unsuspected drug overdose, a new study found, offering grave implications for the epidemiology of overdose mortality.
“In most cases, a determination of sudden cardiac death is actually a presumed diagnosis,” said Zian Tseng, MD, a professor of cardiology and a cardiac electrophysiologist at the University of California San Francisco. “It means death within an hour of symptom onset. The cause is a pure guess. You won't know the actual cause unless you do an autopsy.”
That is precisely what Dr. Tseng and his colleagues did. Building on the parent San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) study (Circulation. 2018;137:2689; https://bit.ly/2GsqbyB), the researchers conducted a case-series analysis of all patients aged 18 to 90 who had an out-of-hospital cardiac arrest attended by EMS between Feb. 1, 2011, and March 1, 2014.
All received full autopsies, full blood toxicology, and adjudication of the cause of death by a medical examiner, cardiac pathologist, neurologist, and two cardiologists or cardiac electrophysiologists using the criteria of the Cardiac Arrest Registry to Enhance Survival (CARES) and the World Health Organization. (Ann Intern Med. 2020 Aug 11. doi: 10.7326/M20-0977.)
The study identified 541 people with sudden cardiac death, 525 of whom had a full autopsy and were included in the original POST SCD study. The cohort was extended from March 1, 2014, to Dec. 31, 2017, with 242 people with out-of-hospital cardiac death undergoing autopsy by the medical examiner.
Canary in the Coal Mine
The researchers compared those with sudden death who were found on autopsy to have occult fatal overdoses with those whose deaths were attributed to other causes. They determined that 15 percent of 525 cases deemed to be out-of-hospital cardiac arrests were actually drug overdoses, and that 22.3 percent of the 242 out-of-hospital cardiac arrests in the extension study were occult overdoses.
A medical toxicologist reviewed toxicology reports to determine the classes of drugs and metabolites involved, and Dr. Tseng's group evaluated drug lists and prescriptions from the prior year, along with non-prescription drugs identified in the toxicology report. Most of those with overdose deaths tested positive for multiple drugs of various types, and 50 percent in the original cohort and 42.3 percent in the extension group did not have prescriptions for those drugs from the past year.
The parent study found that nearly half of sudden deaths were not cardiac, and Dr. Tseng said occult overdose was the chief non-cardiac cause of the sudden deaths.
The authors added that sudden death was the first manifestation of cardiac disease for more than half of all autopsy-defined sudden arrhythmic deaths. Leading causes of presumed sudden cardiac deaths were coronary disease (32%), occult overdose (13.5%), cardiomyopathy (10%), cardiac hypertrophy (8%), and neurological conditions (5.5%).
“This could be the canary in coal mine,” Dr. Tseng said. “It is likely that these deaths are missed on a large scale throughout the country.”
The federal Centers for Disease Control and Prevention in Atlanta found that 7936 of 16,236 drug overdose deaths in 24 states and the District of Columbia involved opioids without stimulants, 2056 involved stimulants without opioids, 5301 involved opioids and stimulants, and 943 involved neither. (MMWRMorb Mortal Wkly Rep. 2020:69:1189; https://bit.ly/38cxuG0.) About 80 percent of overdose deaths involved opioids, and three of four involved illicitly manufactured fentanyl. Understanding the characteristics of this epidemic could inform prevention efforts, the CDC noted.
Drug overdose interventions should address the combination and lethality of the drugs being used (e.g., illicitly manufactured fentanyl in combination with stimulants) and also prevent prescription drug misuse (e.g., inappropriate prescribing) and illicit drug use. The report's finding that nearly 85 percent of overdose deaths involved illicitly manufactured fentanyl, heroin, cocaine, or methamphetamine reflects rapid and continuing increases in the supply of fentanyl and methamphetamine coupled with illicit concurrent use of opioids and stimulants.
Autopsy is the gold standard for recognizing occult overdose deaths, but most medical examiners are not equipped to handle that volume or kind of work. “It is indisputable that sudden cardiac death (SCD) has been and remains a major population burden,” wrote Robert Myerburg, MD, a professor of medicine and physiology at the University of Miami Miller School of Medicine, in an editorial accompanying the parent study. (Circulation. 2018;137:2701; https://bit.ly/34XozGL.)
“The conclusion that 40% of events appearing to be [sudden cardiac deaths] were not sudden or unexpected is sobering and requires our attention as we classify [sudden arrhythmic deaths] in the design and execution of future studies.... The converse perception, that the cumulative numbers still contain a large representation of events that are indeed cardiac-based [sudden cardiac deaths] and that there may be some undercounting, should not be lost as a result of the principles elucidated in this study,” he wrote.
Dr. Tseng concluded, “If we take our results at face value, then we have to qualify what we call a cardiac arrest as a presumed sudden cardiac death until it's proven to be cardiac with a post-mortem investigation. And when you look at it systematically, it's not a surprise. Why should they all be cardiac?”
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Ms. SoRellehas been a medical and science writer for more than 40 years, previously at the University of Texas MD Anderson Cancer Center, The Houston Chronicle, and Baylor College of Medicine. She has received more than 60 awards, including the Texas Human Rights Foundation Award. She has been a contributor to EMN for more than 20 years.