Latest on Catheter interventions on the pulmonary valve and Infective Endocarditis

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1 Latest on Catheter interventions on the pulmonary valve and Infective Endocarditis Andreas Eicken Deutsches Herzzentrum München, Klinik für Kinderkardiologie und angeborene Herzfehler, Technische Universität München

2 Potential conflict of interest: Proctor for Medtronic Melody valve

3 WHAT IS INFECTIVE ENDOCARDITIS (IE)? IE is an infection of the endocardium (usually bacterial) or prosthetic surfaces in the heart May include one or more heart valves, the mural endocardium, or a septal defect PATHOGENESIS OF IE a. Pathogens gain access to bloodstream b. Pathogens adhere to valve surface c. Some pathogen species gain entry to cells, causing inflammation of tissue d. Pathogens proliferate leading to maturation of vegetation on valve e. Embolization of vegetation particles and systemic spreading of the pathogens often occurs Adapted from Werdan, K. et al Nat. Rev. Cardiol.

4 IE AND BIOPROSTHETIC VALVES Infective endocarditis (IE) is a potential late complication associated with ALL types of bioprosthetic valve implants SURGICAL TRANSCATHETER including RV-PA Conduits SAPIEN TM* THV CoreValve TM TAVR Melody TM TPV

5 DIAGNOSIS OF IE Criteria have been developed to diagnose IE, but not directly applicable to prosthetic valves or right-heart-specific Duke Criteria (developed 1994) often used as guidelines but has limitations MODIFIED DUKE CRITERIA: 2 major or 1 major+3 minor or 5 minor Developed for native valve endocarditis Applicability to prosthetic valve endocarditis (including transcatheter valves) is questionable New valvular stenosis not listed in Duke criteria, but indicative of IE in prosthetic valves Echo Inconsistent & Unreliable Always Add TPV stenosis Almost never Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. American Journal of Medicine. 96(3):200-9, 1994 Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria fort he diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:

6 DIAGNOSIS OF IE Blood cultures May be most specific / sensitive TTE Not ideal for adult patients, patients with multiple surgeries or multiple stents TEE Limited RVOT imaging CT/PET/SPECT ICE Potential limitations of diagnostic modalities: May be difficult to visualize RVOT and leaflets using echocardiography making it challenging to identify bacterial vegetations 1 Also makes it difficult to distinguish between TPV-related and TPVunrelated IE Blood cultures and TEE are more often negative for endocarditis in prosthetic valves than in native valves 2 Echo neg. in as many as 70% CHD-IE 3 1ESC Guidelines on Infective Endocarditis, Habib et al., European Heart Journal, Cheung, et al, Intl J of Cardiology, 2015

7 MODIFIED CRITERIA FOR DIAGNOSIS OF IE ESC Task Force proposed that the sensitivity of the Duke criteria can be improved by new imaging modalities (MRI, CT, PET/CT) that allow the diagnosis of embolic events and cardiac involvement when TTE/TOE findings are negative or doubtful 2015 ESC Guidelines for the management of infective endocarditis; European Heart Journal (2015) 36, doi: /eurheartj/ehv319 1 May include cerebral MRI, whole body CT, and/or PET/CT

8 MODIFIED CRITERIA FOR DIAGNOSIS OF IE The ESC Task Force proposes the addition of three further points in the diagnostic criteria (modified Duke Criteria): (1) The identification of paravalvular lesions by cardiac CT should be considered a major criterion (2) In the setting of the suspicion of endocarditis on a prosthetic valve, abnormal activity around the site of implantation detected by 18F-FDG PET/CT (only if the prosthesis was implanted for >.3 months) or radiolabelled leucocyte SPECT/CT should be considered a major criterion (3) The identification of recent embolic events or infectious aneurysms by imaging only (silent events) should be considered a minor criterion 2015 ESC Guidelines for the management of infective endocarditis; European Heart Journal (2015) 36, doi: /eurheartj/ehv319 Definitions of the terms used in the European Society of Cardiology 2015 modified criteria for the diagnosis of infective endocarditis Major criteria 1. Blood cultures positive for IE a. Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus gallolyticus (Streptococcus bovis), HACEK group, Staphylococcus aureus; or Community-acquired enterococci, in the absence of a primary focus; or b. Microorganisms consistent with IE from persistently positive blood cultures: 2 positive blood cultures of blood samples drawn > 12 h apart; or All of 3 or a majority of 4 separate cultures of blood (with first and last samples drawn 1 h apart); or c. Single positive blood culture for Coxiella burnetii or phase I IgG antibody titre > 1: Imaging positive for IE a. Echocardiogram positive for IE: Vegetation; Abscess, pseudoaneurysm, intracardiac fistula; Valvular perforation or aneurysm; New partial dehiscence of prosthetic valve. b. Abnormal activity around the site of prosthetic valve implantation detected by F-FDG PET/CT (only if the prosthesis was implanted for >3 months) or radiolabelled leukocytes SPECT/CT. c. Definite paravalvular lesions by cardiac CT. Minor criteria 1. Predisposition such as predisposing heart condition, or injection drug use. 2. Fever defined as temerature > 38º C. 3. Vascular phenomena (including those detected by imaging only); major arterial emboli, septic pulmonary infarcts, infectious (mycotic) aneurysm, intracranial haemorrhage, conjunctival haemorrhages, and Janesway s lesions. 4. Immunological phenomena; glomerulonephritis, Osler s nodes, Roth s spots and rhumatoid factor. 5. Microbiological evidence; poitive blood culture but does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with IE

9 DIAGNOSIS OF IE IS INCONSISTENT Comparison of IE rates across publications is difficult as IE is not always equally defined Need standardized definitions and reporting criteria Rates as published may be over-estimated due to low threshold for IE diagnosis Rates may be under-estimated due to under-reporting and/or lack of follow-up IE Incidence may be reported as cumulative - or as IE cases per patient year Streptococci Staphylococci

10 Prosthetic valve IE AoV surgery IE occurs in 3-4% of patients within 5 years of index surgery and affects mechanical - and bioprosthetic valves equally > 1/3 cases are health-care-acquired Early prosthetic IE (< one year post surgery) = within the first 2 months after index surgery ( causative are usually staphyloccoci species) IE > 1 year: causative organisms are the same as in native valve IE S.aureus prosthetic IE has a 1 year mortality rate up to 50% Cahill TJ, Pendergast BD. Infective endocarditis.lancet 2016,387:

11 Incidence of IE after TAVI/TAVR Amat-Santos et al. Circulation 2015;131: IE/7944pts post TAVR (US registry) IE incidence was 0.67%/1.1 patient years (0.5%/patient year) Olson NT et al. Circ Cath Interv 2015;8:e001939; TAVI with Core valve IE 18/509; annualized IE incidence 2.1%, follow-up 1.4y Regueiro et al. JAMA 2016;316: IE/20006pts post TAVR; 47 centers from Europe, USA, and South Am. Overall IE incidence of 1.1% per patient year, onset 5.3 months after TAVR But TAVR and PPVI patient groups differ significantly, patients after PPVI have a life expectancy of decades not years/months

12 PPVI/PTVI Experience DHM 12/ /2018 n = 270 valve-in-valve n = 6 age median (y) 18.9 ( ) weight (kg) 59 (18-176) Gender f = 100, m = 170 OP 2 (1-6) diagnosis TOF/PA 123 TAC 41; TGA 21, AoVS 28, other 57 conduit Homograft 174, none 27, Hancock 8, Shelhigh 4, Matrix 1, Contegra 11, other 45; Valve position PaV 248, TrV 22, TCPC 1, other 1, MiV 1 valve Melody 239, Sapien 23 n = 5 Sapien 26 n = 17; Sapien 29 n = 9

13 PPVI vs PVR DHM Prospective study Surgery only if PPVI is not possible -Coronary anatomy -Wide RVOT

14 PPVI vs PVR DHM P : n.s. 91% of our PPVI patients live with their PPVI valve surgery PPVI

15 PPV and IE DHM IE 15 pts 17 episodes Cum. Incidence 6 % Management IE Medical 9 Surgery 8 total patient years up to now 942 years Annual incidence of IE 1.8%/per pat/year Tanase et al. IJC 2018 revision submitted

16 first valve implanted valves longest follow up 11 years 6 years patient years annualyzed incidence 17/942 = 1.8%? Tanase et al. IJC 2018 revision submitted

17 What to do in suspected IE? Suspected IE after PPVI Blood cultures 6 in 48 hours TEE, ICE, CT, PET i.v. antibiotics (6 weeks) Hemodynmic instability severely sick ICU, instant surgical treatment Symptomatic patient search for thrombi (ICE, CT, PET) Decision: medical treatment feasible 6 weeks of i.v. antibiotics, then blood cultures

18 IE treatment 9 year old girl 27kg, TAC with 12 mm Contegra 06/2016 PPVI ccp + Melody Res. Grad 15 mmhg 6 months later, Septic shock, muliple abcess, Staph aureus Emergency surgery Contegra 20 Now alive and well RVP 39mmHg Oscillating thrombus in Melody valve in TTE

19 IE treatment 34 year old m 67 kg Cc-TGA, allograft Lv-PA; Melody fever, CRP Aggregatibacter aphrophilus (hämophilus) in blood culture Grad LV-PA 4 m/s 6 weeks of AB, july m/s flow lv-pa Patient NYHA 1 ICE examination because TEE and TTE did not visualize the valved Conduit; oscillating thrombi at the distal allograft, valve leaflets thickened

20 IE BJV vs others Melody vs Contegra Berlin 2017

21 Sharma et al. IE in RVOT Bioprosthesis Cumulative IE incidence = dividing the number of IE cases by the number of patients at risk as a percentage Melody data are often prospectively acquired whereas the data from the homograft and bioprosthesis valves are collected retrospectively

22 Abdelghani M. et al. IE after Melody valve Implantation in pulmonary position EHJ 2017 abstract

23 Bacterial Adherence BJV Selective adhesion of S. aureus and S. sanguinis pathogenic strains to Melody valve tissue was noted on healthy tissue and increased after implantation procedural steps. Jalal Z, Galmiche L, Lebeaux D et al. Selective propensity of bovine jugular vein material to bacterial adhesions: An in-vitro study. Int J Card 2015;198:201-5 Our data provide evidence that the surface composition of BJV and CH tissue themselves, bacterial surface proteins, and shear forces per se are not the prime determinants of bacterial adherence. Veloso TR, Claes J, Van Kerckhoven et al. Bacterial adherence to graft tissues in static and flow conditions. JTCVS 2017:1-8

24 Melody vs Sapien Hascoet S et al.2017 JACC Card. Interv. 10(5); PPVI in 79 patients (Melody valve 32, Sapien valve 47) IE n = 8/32 (25%) only after Melody; one patient died of sepsis, 4 elective surgical valve removal and 2 delayed surgical removal, 1 re-ppvi After the initially high IE incidence protocol was changed to a 3 day antibiotic regime, more accent on infection prevention and only Sapien Median follow-up Melody: 4.9 years compared to Sapien 1.0 years Conclusion Hascoet et al.: IE after PPVI may be less common with the Sapien compared with the Melody valve.

25 Sapien PV Compassion Trial

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27 conclusion all patients with bioprosthetic valves are at risk for IE In our patient cohort cumulative IE rate was 6%, and annual incidence was 1.8 %/patient year. So far, all of our patients treated for IE after PPVI survived during PPVI, we aim to achieve the best possible hemdynamic result (residual gradient < 15 mmhg, meticulous preparation of the landing zone; avoiding post dilatation with high pressure balloons) In suspected IE after PPVI key is clinical risk assessment and visualization of the implanted valve to decide on the adequate management strategy

28 conclusion robust comparative data for surgical RVOT prostheses is not available, so the relative risk with PPVI (Melody TM TPV/Sapien) is difficult to estimate prophylaxis to aid in prevention of IE are key after all bioprosthetic valve implants (surgically and catheter delivered) anticoagulation may lower the incidence of primary thrombus formation PPVI continues to provide a safe and beneficial therapeutic option for CHD patients with failed RVOT conduits, delaying their next surgical intervention

29 conclusion 91% of our PPVI patients live with their PPVI valve surgery PPVI

30 Conclusion Thank you! Istanbul AEPC 2012

31 Endocarditis and surgical PVR Khanna AD et al. Benchmark outcomes of pulmonary valve replacement using the Society of Thoracic Surgeons Database. Ann Thorac Surg 2015;100: At baseline 20/6431 (0.3%) in STS-Congenital Heart Surgery Database (age 17y, male 59%, in-hospital mortality 0.9%) And 409/3352 (12%) in the STS-Adult Cardiac Surgery Database (age 41y, male 57%, in-hospital mortality 4.0%) had had endocarditis

32 PPVI/PTVI Experience DHM total pulmonal tricuspidal IVC mitral Melody Sapien

33 942 patient years for Melody valve CHD RV-PA connection Prior to PPVI onset IE after PPVI (month) Gender History of IE microorganisms 1 TAC Allograft 4 m - Coagulase-negative staphylococci 2 PA+VSD nativ 4 f - Staphylococcus epidermidis 3 TAC Allograft 6 m - Stapyhylococcus aureus 4 TAC Contegra 6 f - Stapyhylococcus aureus 5 AS Allograft 9 m + Stapyhylococcus aureus 6 TAC Allograft 12 f - Streptococcus mitis TAC Melody 32 f + Staphylococus aureus 7 TOF Allograft 21 m - Streptoccocus viridans 8 PA+VSD Hancock 22 m - Hämophilus parainfluenza 9 PA+VSD Contegra 34 f - Steptococcus spperficialis 10 cctga Allograft 52 m - Stapyhylococcus aureus 11 PA+VSD Allograft 58 f - Staphylococcus hominis 12 cctga Allograft 60 m - Aggregatibacter aphrophilus ctga Melody 15 m + Streptococcus anginosus 13 TAC Allograft 62 m - Staphylococcus epidermidis 14 TOF Allograft 81 f - Corynebacterium striatum 15 TAC Allograft 91 f - Streptococcus parasanguinis Tanase et al. IJC 2018 revision submitted

34 PPVI vs PVR DHM Surgery (21 Yrs) PPVI (21 yrs)

35 DEFINING AND DIAGNOSING TPV INVOLVEMENT TPV related typically not just the valve Potentially either the valve or vein segment wall Manifestation of TPV involvement Vegetation not always present Obstruction common Pulmonary regurgitation rare Most frequent causative pathogens Streptococci Staphylococci Enterococci Suspected IE Patients with fever & change of valve function (increased gradient or new Pulmonary Regurgitation (PR) should be considered and treated as potential IE, even in presence of negative blood cultures Published reports recommend physicians institute therapy when IE is suspected regardless of whether or not the Duke Criteria has been met 1 1 McElhinney et al., Circulation: Cardiovascular Intervention, 2013 Berlin 2017

36 IE treatment 32 year f 58 kg TAC, CM AoV, Allograft 21 RV-PA 22q MaxLD and Melody 20 Mullins 2015 IE with Str. parasanguis, Echo 3.3ms RV-PA 6 weeks AB july m/s RV-PA no PR ICE examination because TEE and TTE did not visualize the valved Conduit; oscillating thrombi in the valved conduit Berlin 2017

37 DECISION TREE MANAGEMENT OF IE Berlin 2017

38 HOW TO CHARACTERIZE IE Endocarditis is a time-related adverse outcome - pattern over time may or may not be linear or predictable Incidence Simple proportion of cases/patients at risk Time-independent Can never decrease within a given cohort Freedom from endocarditis Estimated probability of freedom from event over time Can be depicted graphically, broken down into phases, etc. Can never increase within a given cohort Annualized rate Simple proportion of cases/cumulative patient-years of risk Assumes linear or otherwise consistent rate over time Can increase or decrease within a given cohort Berlin 2017

39 HOW TO CHARACTERIZE IE Endocarditis is a time-related adverse outcome - pattern over time may or may not be linear or predictable Berlin 2017

40 Berlin 2017