Issues in Cardiac Procedures for Drug Use-Associated Infective Endocarditis 

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As the opioid epidemic worsens, rates of drug use-related infective endocarditis and associated procedures have grown substantially.
Rates of drug use-related infective endocarditis and procedures to treat infective endocarditis continue to increase in the United States.

Rates of infective endocarditis (IE) and associated procedures have grown substantially in the United States (US) in recent years due to increasing intravenous drug use (IVDU) in the setting of the worsening opioid epidemic. Studies have shown a 681% increase in hospital admissions for drug use-associated IE (DUA-IE) in West Virginia between 2014 and 2018, for example, and a 12-fold increase in such admissions in North Carolina hospitals between 2007 and 2017.1,2

Other findings suggest that 1 in 10 patients receiving cardiac care in the intensive care unit (ICU) uses illicit drugs.3 This trend presents various challenges to cardiac surgeons, including risk assessment and resource allocation issues for patients who are known to have worse outcomes and high rates of reinfection after a procedure compared to patients whose disease is not associated with drug use.4 

Outcomes in DUA-IE vs Non-DUA-IE

In a 2018 retrospective cohort study, researchers used propensity matching to compare cardiac procedure outcomes between US patients with opioid use disorder (OUD; n=11,359) and without OUD (n=5,707,193) from the Nationwide Inpatient Sample database.5 Procedures included coronary artery bypass graft, valve surgery, and aortic surgery, with higher rates of valve and aortic surgeries noted among patients with OUD (49.8% vs 16.4%; P <.001).

While similar mortality rates were observed in patients with and without OUD (3.1% vs 4.0%; P =.12), the overall incidence of major complications was significantly higher among those with OUD (67.6% vs 59.2%; P <.001), including blood transfusion (30.4% vs 25.9%; P =.002), pulmonary embolism (7.3% vs 3.8%; P <.001), mechanical ventilation (18.4% vs 15.7%; P =.02), and prolonged pain (2.0% vs 1.2%; P =.048).5

The main challenges relate to the patient population itself. IVDU patients are typically not very compliant and have high rates of recurrent infection because of continued drug use after surgery.

A study published in 2020 analyzed 228 valve procedures performed at a single US tertiary hospital between 2002 and 2016, of which 35% were DUA-IE cases.6 The results demonstrated higher overall mortality (48% vs 32%; P =.025) and a higher risk of overall mortality (adjusted hazard ratio, 2.41; 95% CI, 1.38-4.20; P =.002) in patients with DUA-IE compared with those with non-DUA-IE. The findings further showed that DUA-IE was linked to higher mortality rates during the midterm postoperative period (53% vs 31%; P =.003).

In addition, patients with DUA-IE were found to have longer (median, 27 vs 17 days) and more expensive (median, $250,994 vs $198,764) hospital stays compared to patients with non-DUA-IE.2

Following cardiac procedures, studies have reported readmission rates of 22% to 49% in DUA-IE patients and continued injection drug use in at least one-third of cases.7 In research published in 2020, the number of reoperative valve surgeries for DUA-IE at 8 US centers increased from 19% in 2012 to 28% in 2017 (P <.001), and these patients demonstrated higher 30-day mortality rates (8.1% vs 4.8%; P =.049).compared to those receiving first-time valve surgery.8

An Ethical Dilemma

In an ongoing ethical debate, some experts have even wondered if people who inject drugs should receive a second valve replacement surgery in the context of continued drug use.9 According to results of several surveys, up to one-half of cardiothoracic surgeons indicated reluctance to provide surgery for native valve DUA-IE, while approximately 25% to 36% of surgeons indicated willingness to reoperate on DUA-IE in patients with prosthetic valve DUA-IE and continuing drug use following the previous surgery.10

Additionally, two-thirds of surgeons reported that they had previously refused surgery for DUA-IE for reasons related to the “personal choice to use drugs, ‘recidivism,’ and inappropriate spending of medical dollars as contraindications to surgical therapy,” wrote the authors of a 2022 review published in the Journal of Cardiac Surgery.10

However, other experts note that despite the poor outcomes associated with persistent postoperative drug use in individuals with DUA-IE, these patients may have lacked access to adequate substance use treatment at the time of the initial surgery. Thus, it is inappropriate to deny surgery to those with recurrent disease based on anticipated relapse risk.10

To gauge clinician perspectives on the topic, we interviewed Ismail El-Hamamsy, MD, PhD, FRCSC, the Randall B. Griepp Endowed Professor of Cardiovascular Surgery at the Icahn School of Medicine at Mount Sinai and director of aortic surgery for Mount Sinai Health System in New York; Harold L. Lazar, MD, cardiothoracic surgeon at Boston Medical Center and professor of cardiothoracic surgery at Boston University School of Medicine; and Hamza Aziz, MD, assistant professor of surgery in the division of cardiac surgery at Johns Hopkins University School of Medicine in Baltimore.

What are some of the top challenges in cardiac surgery for DUA-IE compared to non-DUA-IE?

Dr El-Hamamsy: The main challenges relate to the patient population itself. IVDU patients are typically not very compliant and have high rates of recurrent infection because of continued drug use after surgery. Additionally, infections can more often occur in IVDU patients than in non-IVDU patients and be caused by drug-resistant organisms or fungi, which are more invasive and harder to eradicate. 

Dr Lazar: There are several challenges for patients with DUA-IE, including a higher chance of developing recurrent IE after surgery and significantly higher mortality if they require a reoperation. One-third of these patients die from drug overdose or recurrent IE following their initial surgery. Recidivism is the strongest predictor of mortality in DUA-IE patients and is the biggest challenge faced in treating these patients.11

Dr Aziz: The biggest challenge for me in DUA-IE is knowing I am not treating the disease but a symptom of the disease, whereas in non-DUA IE, I am eliminating the disease by removing the infection and making patients better. 

The second aspect is that DUA-IE patients are in the hospital for 6 weeks while they get their IV antibiotics. As I get to know their life stories and circumstances, I gain insight into how challenging these people’s lives have been and the fact that the odds of success in life were not in their favor from the time they were kids. Oftentimes, their parents were the ones who introduced them to drugs. 

Lastly, I have had patients who had tremendous recovery in the hospital and show so much promise only to relapse once they go “home,” wherever that may be, and re-infect the valve.

What are recommendations for clinicians in addressing these challenges?

Dr El-Hamamsy: The approach in patients with DUA-IE must be more holistic. Treating the infection alone is unlikely to cure the patient because of the high risk of recurrence due to continued drug use. Instead, a multidisciplinary approach which includes addiction medicine, social workers, and close monitoring after discharge are key to limit the risks of recurrence and to avoid surgical futility.

Dr Lazar: An in-house endocarditis heart team is currently recommended for DUA-IE patients.11 Along with participation from cardiac surgeons, infectious disease, addiction medicine, psychiatry, and nursing, social workers can help with initiating inpatient addiction programs and facilitating discharge to inpatient facilities that can manage IV antibiotics and provide drug addiction treatment. This model could decrease recidivism as well as morbidity and mortality in these high-risk patients.

In a 2020 paper, Ahmed and Safdar discuss an ethical dilemma about whether patients with DUA-IE who receive valve replacement surgery and continue to use drugs should receive a second surgery.9 What are your thoughts about this issue?

Dr El-Hamamsy: This continues to be a great ethical and practical dilemma. On paper, it is easy to argue against major resource mobilization if the patient continues their drug abuse, as these treatments are often futile and consume huge resources. In practice, however, it is very difficult as a surgeon to deny these—often young—patients their only chance of surviving their current infection. 

This highlights the importance of a multidisciplinary team, which includes an ethicist to help make some of these difficult decisions. Ultimately, these are always case-by-case decisions. There are no blanket rules.

Dr Aziz: I do believe in giving patients who relapse a second chance. Most surgeons who have been doing it long enough have had success stories with patients who went clean after their second or even third valve intervention. In the end, it’s an individualized case-by-case decision.

What are the most pressing remaining needs in this area?

Dr El-Hamamsy: The most pressing needs are the realization that DUA-IE is far more than a pure cardiac surgical problem. It requires the creation and implementation of a multidisciplinary team aimed at accompanying the patient after discharge through a journey to rehab and drug cessation. This requires dedicated resources and specific expertise.

Dr Lazar: Many DUA-IE patients lack stable housing and face barriers in access to outpatient drug and rehab programs due to lack of medical insurance and transportation. They may live in areas with a scarcity of options for drug addiction treatment, and some hospitals lack inpatient or outpatient programs for the treatment of drug addiction to prevent recidivism in these patients. 

Addressing these issues involves proper inpatient and outpatient therapy to treat IVDU and prevent recidivism following surgery. Increasing access to these options will require the support of hospital and government resources and third-party payers.

Dr Aziz: In terms of advancements in treatment strategies, I think percutaneous technologies that can “debulk” vegetations safely, not only on the tricuspid valve but also on the mitral and aortic valve, will be quite helpful.

References:

  1. Bhandari R, Alexander T, Annie FH, et al. Steep rise in drug use-associated infective endocarditis in West Virginia: characteristics and healthcare utilization. PLoS One. Published online July 15, 2022. doi:10.1371/journal.pone.0271510
  2. Schranz AJ, Fleischauer A, Chu VH, Wu LT, Rosen DL. Trends in drug use-associated infective endocarditis and heart valve surgery, 2007 to 2017: a study of statewide discharge data. Ann Intern Med. 2019;170(1):31-40. doi:10.7326/M18-2124
  3. European Society of Cardiology. Illicit drugs are used by one in ten intensive cardiac care unit patients. ScienceDaily. August 26, 2022. Accessed October 9, 2022.
  4. Yucel E, Bearnot B, Paras ML, et al. Diagnosis and management of infective endocarditis in people who inject drugs: JACC state-of-the-art review. J Am Coll Cardiol. Published online May 16, 2022. doi:10.1016/j.jacc.2022.03.349
  5. Dewan KC, Dewan KS, Idrees JJ, et al. Trends and outcomes of cardiovascular surgery in patients with opioid use disorders. JAMA Surg. Published online December 5, 2018. doi:10.1001/jamasurg.2018.4608
  6. Wurcel AG, Boll G, Burke D, et al. Impact of substance use disorder on midterm mortality after valve surgery for endocarditis. Ann Thorac Surg. Published online October 16, 2020. doi:10.1016/j.athoracsur.2019.09.004