Infective Endocarditis Due to Opioid Addiction: Two Diseases, Highly Divergent Outcomes

Surgery for infective endocarditis (IE) in people who use injected opioids is as successful as in nonusers of opioids, yet most patients soon relapse to opioid use and die within three to five years of surgery, a Cleveland Clinic study has found.

The study, published in the Journal of the American College of Cardiology (2024;83:811-823), concludes that opioid addiction is considerably more lethal than IE surgery itself and requires enhanced and comprehensive rehabilitative efforts.

“It is disheartening and draining when we hear that one of our patients has been readmitted for relapse or has overdosed and died,” says corresponding author Haytham Elgharably, MD, Surgical Director of Cleveland Clinic’s multidisciplinary Endocarditis Center. “We view these cases as involving two diseases — endocarditis and addiction — and treatment for endocarditis cannot ultimately be effective unless the addiction is overcome. We remain committed to refining efforts to combat the addiction and will continue to track outcomes in these patients.”

Backdrop to the study

A large share of IE cases requiring heart surgery result from use of injected opioids. “The epidemic of opioid use disorder has continued to impact U.S. communities with devasting legacies,” says infectious disease physician Steven Gordon, MD, a member of the Endocarditis Center team and a study co-author. “The latest surveys indicate that 2 in 5 Americans know someone who fatally overdosed and 1 in 8 say fatal overdose has ‘disrupted’ their lives.”

Cleveland Clinic has one of the most active IE surgery programs in the country. “People who inject drugs who present with IE commonly require complex heart valve repair or aortic root reconstruction,” notes study co-author and cardiothoracic surgeon Shinya Unai, MD. “Some may have had prior surgery for endocarditis, which makes the operation even more complex.”

Study essentials

To prevent relapse and avoid IE recurrence, Cleveland Clinic’s Endocarditis Center supports patients who inject drugs with a multidisciplinary program of pre-, peri- and postoperative care, with a focus on preventing return to addiction.

Despite these efforts, addiction relapse and death rates have not been slowed in recent years, according to the results reported in JACC. The retrospective study included 227 persons who injected drugs (mean age, 36) who underwent IE surgery at Cleveland Clinic from January 2010 to June 2020. Of the 227 operations, 67 (30%) were reoperations, seven were second reoperations and one was a third reoperation.

Psychosocial comorbidities were common, with 66% of patients reporting arrest, incarceration or other involvement with the justice system; 25% being unhoused; and 52% and 46% having a diagnosis of depression or anxiety, respectively.

The most commonly used injected drug was heroin, reported by 81% of patients, although the study authors note that drug enforcement agencies believe that “heroin” is now more likely to be a fentanyl derivative with fillers. Fentanyl is often combined with xylazine, a drug that is more dangerous because it is not reversible with naloxone.

Early surgical outcomes in the cohort were excellent and equivalent to those of IE patients without opioid addiction. However, a sizeable share of patients was lost to follow-up, and rates of relapse to opioid use were high, particularly in the first year, peaking at nine months after surgery.

Because of the high loss to follow-up, the researchers calculated patient outcomes as conditional probabilities. They estimated that, at one year after surgery, 16% of patients had been lost to follow-up, 32% had relapsed and 21% had died. By five years, the estimates were 59% lost to follow-up, 79% having relapsed and 68% having died, with a median time to death of 3.2 years.

Relapse was the only factor significantly associated with death. Predictors of relapse were younger age, heroin use and lower educational attainment.

Addiction far more lethal than endocarditis

“At Cleveland Clinic, we have a large experience in all areas of surgery for endocarditis and have consistently published our results,” says Dr. Unai, noting recent study publications in the Journal of Thoracic and Cardiovascular Surgery (2024;167[1]:127-140, 2023 Epub 15 Feb, and 2023;165[4]:1303-1315). “However, even if the surgical outcomes are good, patients will not have a good long-term result if the addiction is not treated appropriately. We have more work to do.”

There is controversy among surgeons about how to manage these patients — and even whether surgery for IE is appropriate. Cleveland Clinic surgeons believe surgery is not futile.

“Because short-term outcomes are excellent, clinically and ethically we cannot refuse to offer surgery to these patients,” Dr. Elgharably says. “Surgery is not the problem; postoperative care is the challenge.”

The study was conducted in hopes of identifying whether the ongoing addition of supportive efforts was preventing relapses or death. Unfortunately, outcomes were disappointing.

“Of the two potentially lethal diseases these patients have, opioid addiction is far more lethal than advanced IE treated with surgery,” Dr. Elgharably notes. “Although we can prevent immediate death, heart failure, shock and sepsis with surgery, we cannot break the cycle of addiction with what is currently being done. It’s just not enough.”

One encouraging finding was that patients were less likely to be lost to follow-up if they reported having depression or anxiety. “The theory is that we did a better job of treating those psychiatric conditions, and the patients benefited,” says psychiatrist and study co-author David Streem, MD, Medical Director of Cleveland Clinic’s Alcohol and Drug Recovery Center and part of the Endocarditis Center team.

Newer strategies emerging

At the center of Cleveland Clinic’s current efforts to treat IE patients who inject drugs is a program called MOSAIC (Management of Substance Abuse Disorder and Heart Infections in Cardiovascular Patients), which uses standardized protocols for pre-, peri- and postoperative care.

Patients are evaluated preoperatively by a psychiatric addiction specialist, a cardiologist, a cardiac surgeon and an infectious disease physician, who collectively work with patients to put in place a clear plan for postoperative rehabilitation.

In 2017, Cleveland Clinic partnered with a long-term acute care hospital where patients receive treatment for addiction and underlying psychiatric issues while physically recovering from surgery. “This arrangement allows our psychiatrists to improve postoperative discharge follow-up and management, and positions patients to have a better outcome and lower likelihood of returning to drugs,” Dr. Streem explains.

The arrangement was a big win for the Endocarditis Center team, since insurers often refuse to pay for physical rehabilitation services at a facility that provides addiction treatment, due to higher costs.

In 2019, the state of Ohio launched Project SOAR (Supporting Opioid Addiction Recovery), a program promoting community response for people with addiction. By the end of the Cleveland Clinic study in 2020, 100% of IE patients who injected drugs were enrolled in MOSAIC and SOAR, and 100% were discharged on medications for opioid use disorder, versus none in 2010.

After discharge, nurses call patients on a regular schedule to see how they are doing and ask if they need support.

These measures had not slowed the rate of relapse and death during the study period, but the researchers note that there may not have been enough time for an effect to be seen, given that the 10-year study ended in mid-2020.

The Endocarditis Center team continues to try new approaches. Recently, they launched an innovative effort they hope will be more effective in preparing patients for successful recovery. In the “Bridge to Surgery” program, patients presenting with right-sided endocarditis — for which immediate surgery is generally unnecessary — begin addiction recovery along with antibiotic therapy for IE prior to surgery.

A need to lengthen and strengthen postop care

Another focus is extending the duration of recovery programs, in view of the study’s finding that the risk of addiction relapse peaks at nine months after IE surgery.

“Staying in the hospital for two to six weeks and in rehab for four to six weeks is not long enough to get — and remain — sober,” Dr. Elgharably says. He advocates for a state-funded facility where patients can receive addiction treatment for at least six months and a robust staff of social workers and case managers is available to set up patients for success.

“These patients need jobs and a safe environment to return to,” he points out. “Many do not have home environments that are supportive of recovery. Some are homeless. Some have family members who are injecting drugs. When they go back to the same environment, they start injecting again.”

Dr. Streem calls social workers and nurse case managers unsung heroes. “If you have an engaged team of social workers and case managers working alongside addiction specialists, patients are more effectively transitioned through different levels of care,” he says. “I’ve been impressed with the resourcefulness of case managers in transitioning patients out of the long-term acute care hospital with a well-developed treatment plan.”

Study co-author Brian Griffin, MD, a cardiologist with the Endocarditis Center, concurs. “A structured team-centered approach with community involvement and support is essential for optimal long-term outcomes among patients with this daunting treatment challenge,” he says.

Although the opioid epidemic shows little sign of easing, the Endocarditis Center team believes it’s only a matter of time before they find a protocol that reduces the relapse rate and saves lives. While they continue to try new strategies, they invite other centers dealing with the same problem to join the effort.

“Those dying are mostly young people in the prime of life,” Dr. Elgharably says. “This is a problem affecting communities nationwide.”