1. Surgical Outcomes of Infective Endocarditis among Intravenous Drug Abusers: Results from Two Large Academic Centers Joon Bum Kim 1,3, Julius I. Ejiofor 2, Maroun Yammine 2, Sandra B. Nelson 1, Arthur Y. Kim 1, Serguei I. Melnitchouk 1, James D. Rawn 2, Marzia Leacche 2, John G. Byrne 2, Thoralf M. Sundt 1 1 Massachusetts General Hospital and 2 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 3 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

2. Disclosure Joon Bum Kim: 62 nd AATS Graham Traveling Fellow Thoralf M. Sundt: Consultant for Thrasos Therapeutics

3. IV Heroin Use in the United States 314,000 681,000

4. Heroin-Related Deaths Richard et al. N Eng J Med 2015 Major Public Heath Issue 6,000 deaths

5. Background Infective endocarditis among IVDUs: - 100 to 400 per 100,000 person-years (50-100 fold ↑) Risks of Recidivism and Reinfection Shorter life expectancy of IVDUs: Drug intoxication, violence and suicide

6. Background Questions about futility of aggressive, resource-intensive surgical procedures for active IVDUs

7. Study Aim To evaluate - Trends in IVDUs among surgical patients with IE - Outcomes of surgery in IVDUs in the interest of informing decisions on optimal management strategy for these patients

8. Methods Data were pooled from the prospective cardiac surgery databases of two Harvard Medical School affiliated Hospitals: MGH and BWH Queried to identify adult patients (age ≥ 17 years) undergoing heart valve operations due to active infective endocarditis from January 2002 through August 2014

9. Methods Follow-up information: Data from Partners Health Care system ( centralized clinical data registry of all patients encountered) Social Security Death Index search if necessary IRB approval: waived informed consent

10. Subject Patients There were 436 patients who met the enrollment criteria from the two centers (MGH, n=192; BWH, n=244). Overall, 78 patients (17.9%) were current IVDUs

11. IV Drugs of Abuse Heroinn=33 Heroin+Cocainen=19 Heroin+Cocaine+othersn=5 Cocainen=18 Amphetaminen=2 Other polysubstances n=1

12. IV Drugs of Abuse Heroin n=57 (73.1%)

13. IV Drugs of Abuse Cocaine n=42 (53.8%)

14. Proportions of IVDUs among All Surgical Patients with IE

15. Baseline Characteristics IVDU N=78 Non-IVDU N=358 P value Age, yr35.9±9.959.3±14.1<0.001 Female gender38.5%31.0%0.20 Body mass index, kg/m 2 26.7±7.927.8±7.00.24 Ethnicity0.83 White87.2%89.1% Black6.4%3.9% Hispanic1.3%2.5% Asian1.3%1.4% Others3.8%3.1% Age, yr35.9±9.959.3±14.1<0.001

16. Baseline Characteristics IVDU N=78 Non-IVDU N=358 P value Diabetes mellitus7.6%20.7%0.027 Hypertension20.5%62.8%<0.001 NYHA functional class III or IV44.9%49.4%0.46 On dialysis3.8%8.7%0.24 Creatinine clearance, mL/min/1.73m 2 103.5±53.673.1±44.1<0.001 Cigarette smoking history67.9%39.7%<0.001 Current smoking35.9%8.1%<0.001

17. Baseline Characteristics IVDU N=78 Non-IVDU N=358 P value Embolic events46.2%29.9%0.006 Causative pathogens0.14 Viridans Streptococci20.5%24.9% Other streptococci2.6%9.2% Staphylococcus, methicillin-susceptible25.6%20.7% Staphylococcus, methicillin-resistant12.8%18.2% Entercococcus15.4%13.4% Other11.5%6.7% Negative culture11.5%7.0%

18. Baseline Characteristics IVDU N=78 Non-IVDU N=358 P value Single valve affected73.1%82.1%0.068 Aortic valve41.0%55.9% Mitral valve16.7%24.0% Tricuspid valve15.4%2.2% Multiple valves affected,26.9%17.9%0.068 Aortic + Mitral16.7%15.1% Aortic + Tricuspid3.8%1.7% Mitral + Tricuspid6.4%0.6% Aortic +Mitral + Tricuspid00.6%

19. Baseline Characteristics IVDU N=78 Non-IVDU N=358 P value Right-side valve involvement25.6%5.0%<0.001 Vegetation diameter ≥10mm70.5%49.7%<0.001 Abscess formation23.1%33.8%0.066 Prosthetic endocarditis21.8%30.7%0.12 Severe valve dysfunction valves75.6%68.4%0.21 Left ventricular ejection fraction, %59.5±10.460.1±10.90.64 Emergent surgery20.5%23.2%0.61 On IABP3.8%5.0%>0.99

20. Surgical Procedures IVDU N=78 Non-IVDU N=358 P value Primary procedure0.87 Valve repair12.8%9.8% Valve replacement, mechanical23.1%22.6% Valve replacement, bioprostheses44.9%47.8% Valve replacement, allograft19.2%19.8% Associated procedures Aorta replacement6.4%18.4%0.007 CABG12.8%15.6%0.60 Aortic root replacement24.4%26.8%0.78

21. Follow-up Data on mortality: 100% complete - Median, 52.3 months (IQR, 14.0-100.0 months) - 2165.4 patient-years Data on valve-related complications: 76.4% complete - Median, 29.4 mo (IQR, 4.7-72.6 mo) - 570 patient-years

22. Survival 3.8% 13.7% Early mortality P=0.012 P=0.39

23. Freedom from Reinfection and Reoperation

24. Freedom from Event Event-free Survival < 10%

25. Age-Adjusted Outcomes IVDUs vs. Non-IVDUs Adjusted HR95% CIP value Early mortality0.530.11-1.780.34 Late mortality2.771.09-6.720.031 Valve related complications3.071.66-5.68<0.001 Valve re-infection5.362.37-12.13<0.001 Valve reoperation2.991.31-6.790.009 Thromboembolism2.030.58-7.020.27 Hemorrhage2.460.57-10.610.23

26. IVDU Subgroup: Reinfection N=78 Surgical: n=14 Medical: n=14 N=28 (35.9%) Reinfection Early death: n=0 Late death: n=1 Early death: n=3 Late death: n=3 ICH in 3 Profound sepsis in 2 Cardiac arrest in 1 In-hospital IVDU in 3 Resolution in 5

27. Limitations Retrospective analyses Selection bias in the decision to undertake surgery Experiences confined to urban tertiary academic centers Significant follow-up loss

28. Conclusions IVDUs among surgical patients with IE is increasing Although IVDUs are young, with lower cardiovascular risk burdens, long-term clinical outcomes are discouraging: > 5-fold increase in reinfection risk > 2-fold increase in late death This information should be considered when making decisions regarding operative intervention on IE among IVDU

29. Thank you