Infective Endocarditis Deaths Rise as Opioid Crisis Deepens

Mortality due to infective endocarditis (IE) in the United States is spiking among adults in their mid-20s through early 40s, even as adults older than 45 are seeing such death rates plateau or even decrease, according to more than two decades of observational data. The likely reason, researchers say, is the opioid crisis’ disproportionate effect on the young: injection drug use is a major driver of IE risk.

Led by Muchi Ditah Chobufo, MD, MPH (West Virginia University, Morgantown), the study was published online Wednesday in the Journal of the American Heart Association. “The marked acceleration in mortality in the 25- to 44-year age group is a cause for alarm,” the authors say.

Senior investigator Sudarshan Balla, MD (West Virginia University), told TCTMD that the investigators’ interest in the topic was sparked, in part, by personal experience. Balla said that as a fellow in Missouri, he said didn’t see IE that often, but when he began working in West Virginia in 2018, he discovered “it was rampant.” That state, along with Kentucky and Tennessee, saw the most-rapid worsening in IE over the years they analyzed.

“These patients I was seeing were all young,” which is especially troubling, Balla said. The most-obvious explanation for the IE is drug use, “because there is no reason for a young person to otherwise die or get endocarditis. They don’t really have medical conditions, they’re not sick—they’re otherwise pretty healthy.”

Balla said the only way to counteract the rise in IE-related deaths is to deter people from using injection drugs, itself a complicated problem that relates to not only addiction but also access to drugs and social determinants of health.

The CDC WONDER Database

To track the trends, researchers used the US Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to track trends in mortality due to IE from 1999 to 2020. Diagnoses of IE and substance use were based on ICD codes.

Age-adjusted IE-related mortality declined over the 22-year study period, from 26.19 per million people in 1999 to 22.41 per million people in 2020 (an average annual percent change of -0.8; P< 0.001). Declines were seen for men and women, and for all races/ethnicities.

However, the patterns in mortality differed among age groups. For those ages 25-34 years and those ages 35-44 years, mortality rose: average annual percent changes for those groups were 5.4 and 2.3, respectively (P < 0.001 for both). Rates held steady in those ages 45-54 years. And in those 55 and older, mortality declined, with an annual percent change of -0.4 (P = 0.003).

The number of IE deaths in which substance abuse was a contributing cause rose, per 1 million people, over time for those 25-34 years old (from 0.17 in 1999-2006 to 1.29 in 2014-2020) and those 35-44 years old (0.48 in 1999-2006 to 1.26 in 2014-2020). The same was not seen for individuals at older ages. In addition, IE became an increasingly frequent underlying cause of death for the two younger age groups over time.

There is no reason for a young person to otherwise die or get endocarditis. Sudarshan Balla

Mortality rates varied by state, with accelerations seen in Kentucky, Tennessee, and West Virginia (average annual percent changes of 1.2, 0.8, and 2.0, respectively), but not elsewhere.

“We speculate that this acceleration was likely due mainly to the opioid crisis that has engulfed several states and involved principally younger adults,” the investigators write. Injection drug use, they point out, accounts for at least 10% of all IE-related hospital admissions.

There are numerous reasons why Kentucky, Tennessee, and West Virginia were the areas worst hit by the opioid crisis, they explain. “Social determinants such as low wages, unemployment, and high poverty rates have been reported as factors for the high burden of opioid use in these states. These states also were victims of rampant overprescribing of prescription opioid drugs. This led to an increase in the availability of prescription drugs on street markets as well as an increase in the number of individuals using prescription opioids for nonmedical use.”

Harm Reduction Required

Balla acknowledged that their study tracked mortality related to IE, not actual IE prevalence. The most logical explanation, he suggested, is deaths are on the rise because more people are getting IE—not that IE patients are for some reason increasingly more likely to die after being diagnosed with the condition.

“I think most people do survive. There are some patients [with IE] that have really bad heart failure, or they have liver or kidney failure. But most commonly we see strokes, because with infective endocarditis, the vegetations [can] embolize,” he explained. However, risk is higher when patients return to drug use after their initial IE is treated, only to experience another bout.

At a public health level, the only way to decrease IE-related mortality will be harm-reduction programs to address the opioid crisis, he added, though only additional research can show whether these interventions actually work in this setting.

For patients with IE, it’s important both to treat their endocarditis and to ask questions about substance abuse. “If there is a history of injection drug use, we have to involve behavioral medicine and make sure that these patients don’t relapse,” he said.

Future studies should attempt to track the actual prevalence of IE, not just the mortality that stems from it, Balla suggested. Beyond this, “in-depth research is definitely needed to find the reasons for why this is happening. . . . There are a lot of social determinants that are probably at play that need to be addressed.”