Surgical Outcomes of Infective Endocarditis among Intravenous Drug Abusers: Results from Two Large Academic Centers

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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

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

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

Heroin-Related Deaths 6,000 deaths Richard et al. N Eng J Med 2015

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

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

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

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

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

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

IV Drugs of Abuse Amphetamine n=2 Other polysubstances n=1 Cocaine n=18 Heroin+Cocaine+others n=5 Heroin+Cocaine n=19 Heroin n=33

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

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

Proportions of IVDUs among All Surgical Patients with IE

Baseline Characteristics IVDU Non-IVDU P value N=78 N=358 Age, yr 35.9±9.9 59.3±14.1 <0.001 Female gender 38.5% 31.0% 0.20 Body mass index, kg/m 2 26.7±7.9 27.8±7.0 0.24 Ethnicity 0.83 White 87.2% 89.1% Black 6.4% 3.9% Hispanic 1.3% 2.5% Asian 1.3% 1.4% Others 3.8% 3.1%

Baseline Characteristics IVDU N=78 Non-IVDU N=358 P value Diabetes mellitus 7.6% 20.7% 0.027 Hypertension 20.5% 62.8% <0.001 NYHA functional class III or IV 44.9% 49.4% 0.46 On dialysis 3.8% 8.7% 0.24 Creatinine clearance, ml/min/1.73m 2 103.5±53.6 73.1±44.1 <0.001 Cigarette smoking history 67.9% 39.7% <0.001 Current smoking 35.9% 8.1% <0.001

Baseline Characteristics IVDU Non-IVDU P value N=78 N=358 Embolic events 46.2% 29.9% 0.006 Causative pathogens 0.14 Viridans Streptococci 20.5% 24.9% Other streptococci 2.6% 9.2% Staphylococcus, methicillin-susceptible 25.6% 20.7% Staphylococcus, methicillin-resistant 12.8% 18.2% Entercococcus 15.4% 13.4% Other 11.5% 6.7% Negative culture 11.5% 7.0%

Baseline Characteristics IVDU Non-IVDU P value N=78 N=358 Single valve affected 73.1% 82.1% 0.068 Aortic valve 41.0% 55.9% Mitral valve 16.7% 24.0% Tricuspid valve 15.4% 2.2% Multiple valves affected, 26.9% 17.9% 0.068 Aortic + Mitral 16.7% 15.1% Aortic + Tricuspid 3.8% 1.7% Mitral + Tricuspid 6.4% 0.6% Aortic +Mitral + Tricuspid 0 0.6%

Baseline Characteristics IVDU N=78 Non-IVDU N=358 P value Right-side valve involvement 25.6% 5.0% <0.001 Vegetation diameter 10mm 70.5% 49.7% <0.001 Abscess formation 23.1% 33.8% 0.066 Prosthetic endocarditis 21.8% 30.7% 0.12 Severe valve dysfunction valves 75.6% 68.4% 0.21 Left ventricular ejection fraction, % 59.5±10.4 60.1±10.9 0.64 Emergent surgery 20.5% 23.2% 0.61 On IABP 3.8% 5.0% >0.99

Surgical Procedures IVDU Non-IVDU P value N=78 N=358 Primary procedure 0.87 Valve repair 12.8% 9.8% Valve replacement, mechanical 23.1% 22.6% Valve replacement, bioprostheses 44.9% 47.8% Valve replacement, allograft 19.2% 19.8% Associated procedures Aorta replacement 6.4% 18.4% 0.007 CABG 12.8% 15.6% 0.60 Aortic root replacement 24.4% 26.8% 0.78

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

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

Freedom from Reinfection and Reoperation

Freedom from Event Event-free Survival < 10%

Age-Adjusted Outcomes IVDUs vs. Non-IVDUs Adjusted HR 95% CI P value Early mortality 0.53 0.11-1.78 0.34 Late mortality 2.77 1.09-6.72 0.031 Valve related complications 3.07 1.66-5.68 <0.001 Valve re-infection 5.36 2.37-12.13 <0.001 Valve reoperation 2.99 1.31-6.79 0.009 Thromboembolism 2.03 0.58-7.02 0.27 Hemorrhage 2.46 0.57-10.61 0.23

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

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

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

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