1. CIED Infections Incidence, Diagnosis, Microbiology and Prognosis Dr. Adelqui Peralta EP Lab Director Boston VA Healthcare System West Roxbury Campus Assistant Professor of Medicine Harvard Medical School

2. Aging World Population (2025) WHO Aging World Report 2015 The expanding indications for CIED added to an aging population -> Increase in implanted devices Increase in device related complications -> Infections

3. 16-Year Trends in the Infection Burden for Pacemakers and ICDs in the US Greenspon et at JACC 2011

4. 16-Year Trends in the Infection Burden for Pacemakers and ICDs in the US Greenspon et at JACC 2011

5. Incidence of Comorbidities in Patients with CIED Infections Greenspon et at JACC 2011

6. CIED Infection Rates Sandoe et at J Antimicr Chemother 2015 Pathfield et at HR 2015 First Time Implantation: 0.5% to 1%, Replacement/Upgrade: 1% to 5%

7. CIED Infection: Definition  Early superficial site infection:  Presentation within 30 days of operation with wound inflammation, including a “stitch abscess”, no deep infection  Isolated generator pocket infection:  Cellulitis confined to the generator site, including purulent discharge, abscess or erosion in the absence of systemic involvement (negative blood cultures)  Generator pocket infection with bacteremia:  Local infection signs and positive blood cultures  Pocket infection with lead/valvular endocarditis:  Local infection plus positive blood cultures and lead or valvular vegetations  CIED endocarditis without pocket infection:  Positive blood cultures and lead or valvular vegetations but without pocket infection Kusumoto et at HR 2017

8. Microbiology of CIED Infection Sohail al. JACC 2007 N: 189 (138 PM & 51 ICDs) 103 pts (54%) referred for extraction to Mayo Clinic 86 pts (46%) local Mayo Clinic pts Staph 71% Median time: PPM 415 days ICD 125 days p 0.009

9. Microbiology and Pathogens for Patients Who Underwent Lead Explant Device Infection CCF 2000-2011 816 pts: 430 (53%) pocket, 386 (47%) intravasc Hussien et al. JACC EP 2016 Staph 68.4%

10. Microbiology of Early Versus Late* CIED Infections Pocket Hussien et al. JACC EP 2016 *Early vs Late: 1 year Pocket Infection (53% of all CIED) Early vs late (1 year) about 50/50 Early infections more staph aureus Late infections More staph coag neg More MR staph

11. Diagnosis Pocket infection: - More common in early-onset illness (< 1 year of device implantation) - Localized pocket warmth, tenderness, erythema, fluctuance, purulent drainage

12. Diagnosis Pocket infection: Wound dehiscence or erosion of the generator or leads

13. Diagnosis Systemic infection - More common in late-onset infection (>1 year after device implantation) - Fever, chills, sweating, malaise, anorexia, hypotension, embolic lesions, etc. - May present as secondary foci (spinal or pulmonary) Modified Duke Criteria

14. Recommendations for Diagnosis of CIED Infection -Two sets of blood cultures before antibiotics -Pocket aspiration not recommended - At time of explant obtain generator-pocket tissue Gram’s stain & culture and lead-tip cultures

15. 18F-FDG (fluorodeoxyglucose) PET/CT: Useful diagnostic tool in suspected IE and CIED infection Sensitivity: 82%, Specificity: 96% F-FDG PET/CT was able to reclassify 90% of initially classified possible IE by modified Duke criteria 26% reclassified as definite 64% reclassified as rejected Granados et al. JNM 2016

16. Role of FDG PET/CT Scanning  Added value of the test is unclear.  FDG PET/CT is not a sensitive tool for the diagnosis of ICED- LI/IE  It may be useful when there is uncertainty about generator pocket infection.  There is insufficient evidence that FDG PET/CT adds to a clinical diagnosis Sandoe et at J Antimicr Chemother 2015

18. CIED Infection Algorithm Kusumoto et at HR 2017

19. Rate of Cardiac Device Infection According to Type of Bacteremia Maskarinek et al. OFID 2017

20. Incidence of confirmed CIED Infection: 22/62 (35.5%) Incidence of confirmed CIED Infection: 15 of 33 (45.4%).

21. Bacteremia Without Evidence of CIED Infection Kusumoto et at HR 2017

22. Multivariable Model to Predict CIED Infection in Staph Aureus Bacteremia Risk Score:  PPM4  1 device procedure3.5  Duration SAB > 4 days5 Sohail et al. Circ EP 2015 CCF 2000-2011 131 pts with SAB and no signs of pocket infection CIED infection: 45/131 (34%)

23. Staph Aureus Bacteremia: Overall Survival with or Without CIED Infection Sohail et al. Circ EP 2015

24. Prognosis of CIED Infection  30-day mortality rate: ~ 5%,  1-year mortality rate: ~ 15%  7-fold increase in 30-day mortality if CIED is not removed Le et al HR 2011 Viganego et al AJC 2012

25. Prognosis of CIED Infection  > 95% of patients who present with pocket infection or endocarditis can be cured with lead extraction and antibiotics  Early diagnosis of CIED infection, and lead extraction within 3 days of diagnosis are associated with lower in-hospital mortality Le et al HR 2011 Viganego et al AJC 2012

26. Take Home Message  CIED infection occurs with an incidence of ~ 1% in primary implants and least doubles in gen changes and upgrades  CIED infection rates have increased at least partially due to higher comorbidities in device recipients  Staphylococci cause the majority of CIED infections  Up to 15% of CIED infections have negative cultures

27.  Two sets of blood cultures before antibiotics  Adults suspected of having CIED-related endocarditis should undergo TEE  At time of explant obtain generator-pocket tissue Gram’s stain & culture and lead-tip cultures  Routine use of FDG PET/CT scanning is not recommended  Prevention is key Take Home Message