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Carlos-A. Mestres, MD, PhD, FETCS Consultant Cardiovascular Surgery

Carlos-A. Mestres, MD, PhD, FETCS Consultant Cardiovascular Surgery Hospital Clínico. University of Barcelona Barcelona. Spain. Infective endocarditis is an uncommon disease associated to significant morbidity and mortality. As in any infection within the cardiovascular surgery,

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Carlos-A. Mestres, MD, PhD, FETCS Consultant Cardiovascular Surgery

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  1. Carlos-A. Mestres, MD, PhD, FETCS Consultant Cardiovascular Surgery Hospital Clínico. University of Barcelona Barcelona. Spain

  2. Infective endocarditis is an uncommon disease associated to significant morbidity and mortality. As in any infection within the cardiovascular surgery, early diagnosis and aggresive management are indicated Infective endocarditis is a medical & surgical disease which must be managed by a multidisciplinary team with shared interests

  3. The Team The Hospital Clinico of Barcelona Endocarditis Study Group is a multidisciplinary group specifically dedicated to the study and treatment of infective endocarditis and cardiovascular infections operational for 25 years Infectious Diseases (6), Cardiovascular Surgery (3), Microbiology (3), Surgical Pathology (1), Echocardiography (2)

  4. The Team * Infectious Diseases J.M.Miró, A.Moreno, A. Del Río, N. De Benito, X.Claramonte, J.P.Horcajada * Cardiovascular Surgery C.A.Mestres, R.Cartañá, S.Ninot, J.L.Pomar * Microbiology M.Almela, F.Marco, C.García * Surgical Pathology J.Ramírez, N.Pérez * Echocardiography J.C.Paré, M.Azqueta, M.Sitges

  5. Infective Endocarditis What have we learned? What have we changed? What are we doing? Where are we going? An overview

  6. A - Short Courses of Therapy for Infective Endocarditis B - Infective Endocarditis in Drug Abusers (IVDAs) C – Surgical experience

  7. Potential number of candidates for short-courses of therapy for right-sided MSSA endocarditis in IVDAs at the Hospital Clínic of Barcelona, Spain (1979-98) Types of endocarditis in IVDAs MSSA N (%) N - Right-sided IE - Left-sided IE - Mixed IE Total 142 46 16 204 104 (73%) 16 (35%) 10 (64%) 130 (64%) 2 wk Tx* 40% * According to methicillin-susceptibility, HIV status and CD4 cell counts (>200/µL)

  8. Short Courses of Therapy for Infective Endocarditis CONCLUSIONS 5. Patients allergic to penicillin who must receive vancomycin with or without an aminoglycoside must be treated during 4 wks 6. In our 25-year experience, one of every five episodes of native valve IE (general population + IVDAs) and almost one of every two episodes of IE in IVDAs were considered potential candidates for these short courses (2 wks) of therapy

  9. Infective Endocarditis in IVDAs & HIV infection SUMMARY 1. The incidence of IE in IVDA in the AIDS era is decreasing probably due to the change of the drug administration habits in order to avoid HIV-infection 2. HIV-infected IVDA have a higher ratio of right-sided IE and S. aureus endocarditis than HIV-negative IVDA with IE 3. Mortality between HIV-infected or non-HIV-infected IVDA with IE is similar. However, mortality among HIV-infected IVDA is higher in IVDA with less than 200 CD4+ cells/µL or with AIDS criteria

  10. Infective Endocarditis in IVDAs & HIV Infection SUMMARY 4. IVDA with non-complicated MSSA right-sided IE can be succesfully treated with an IV short-course regimen of nafcillin or cloxacillin plus an aminoglycoside during 2 weeks, although the addition of an aminoglycoside may be avoided or reduced to the first 3-7 days 5. Tricuspid valve replacement using mitral homografts can be a safely alternative to tricuspid valvulectomy for those IVDA with endocarditis who need right heart surgery “Long-term results after cardiac surgery in patients infected with the human immunodeficiency virus type-1 (HIV-1)” Mestres CA et al. Eur J Cardio-thorac Surg 2003; 23:1007-1016

  11. Epidemiology 1990 - 2000 Diagnosis of IE 421 IV (IVDA) drug abuse 104 General population 317 Native IE 213 PVE 75 Pacemaker/AICD 29 Admissions/yr >50

  12. “Infective endocarditis in intravenous drug abusers and HIV-1 infected patients” J.M.Miró, A. del Río, C.A.Mestres Infect Dis Clin North Am 2002; 16:273-295 “Infective endocarditis not related to intravenous drug abuse in HIV-1-infected patients: report of eight cases and review of the literature” J.E.Losa, J.M.Miró, A. Del Río, A.Moreno-Camacho, F.Gracia, X.Claramonte, F.Marco, C.A.Mestres, M.Azqueta, J.M.Gatell and the Hospital Clinic Endocarditis Study Group Clin Microbiol Infect 2003; 9:45-54 “Surgical treatment of pacemaker and defibrillator lead endocarditis. The impact of electrode lead extraction on outcome” A.del Río, I.Anguera, J.M.Miró, L.Mont, Fowler VG Jr, M.Azqueta, C.A.Mestres and the Hospital Clinic Endocarditis Study Group Chest 2003; 124:1451-1459

  13. NVE 387 - ADVP 237 - PVE 130 - PM 49 - All 803

  14. PVE 132

  15. S.aureus 274

  16. ICE Presumed intravascular catheter source by region International Collaborationon Endocarditis

  17. Specific indications Mechanical valve Young, “good” ring, cured IE Bioprosthesis Elderly (?), “good” ring, cured IE Homograft Complicated IE, abscess, annular destruction

  18. The complicated root • Root abscess • Aorto-cavitary fistula

  19. Aorto-cavitary fistulae

  20. L770 - AORTO-CAVITARY FISTULIZATION IN COMPLICATED ENDOCARDITIS. CLINICAL AND ECHOCARDIOGRAPHIC FEATURES OF 76 CASES (1992-2001) AND PROGNOSTIC FACTORS OF MORTALITY 42nd ICAAC. San Diego, CA. September 27-30, 2002 The Spanish Aorto-cavitary Fistula Endocarditis Working Group

  21. No clinical infective endocarditis (IE) series have been performed studying the development of aorto-cavitary fistulas (ACF) as a result of spread of infection from valvular tissue towards perivalvular structures. Our aims were to investigate the clinical, echocardiographic and microbiologic features and prognostic factors of in-hospital mortality in patients with IE and ACF. Retrospective and multicentre study at 11 Spanish and 1 North-american Hospitals in patients with IE and ACF.

  22. Spread of infection in infective endocarditis (IE) from valvular structures to the surrounding perivalvular tissue results in periannular complications. Rupture of abscesses and pseudoaneurysms in the sinuses of Valsalva result in the development of aorto-cavitary fistulas and intracardiac shunts. Aorto-cavitary fistula formation is an unusual complication of IE. An incidence of 1% of all cases of IE has been estimated. Fistulization of perivalvular abscesses occurs in 6-9% of cases. Basic considerations

  23. * Multicenter, international, retrospective, descriptive study performed between 1992 and 2001 * Infective endocarditis diagnosed according to Duke criteria * Aorto-cavitary fistulization documented by TTE/TEE * Univariate analysis of prognostic factors of mortality

  24. ACF n Cases IE n Incidence % General population Native valve Aortic Mitral Other PVE Aortic Mitral Other Pacemaker IV Drug abusers OVERALL 69 38 38 -- -- 31 31 -- -- -- 7 76 3147 2105 1056 930 119 872 536 326 10 170 1534 4681 2.2 1.8 3.6 --- --- 3.5 5.8 --- --- --- 0.4 1.6

  25. Clinical characteristics NVE=45 PVE=31 All=76 Mean age (y) Male gender Previous valve disease Comorbidity Mechanical ventilation IV drug abuse Duration of symptoms (d) Duration to Dx of ACF (d) CHF Neuro events Renal failure Peripheral emboli Complete AV block 50.9±18.7* 36 (80%) 13 (28%) 18 (40%) 6 (13%) 7 (16%) 24.5±18.7 36.2±31.6 31 (69%) 8 (18%) 20 (44%) 8 (18%) 5 (11%) 60.2±13.4* 20 (65%) 31 (100%) 9 (29%) 1 (3%) 0 29.8±37.7 44.1±55.5 16 (52%) 4 (13%) 8 (26%) 7 (23%) 6 (19%) 54.7±17.2 56 (74%) 44 (59%) 27 (36%) 7 (9%) 7 (9%) 26.7±27.9 39.4±42.8 47 (62%) 12 (16%) 28 (37%) 15 (20%) 11 (14%)

  26. Pathogens NVE=45 PVE=31 All=76 Staphylococcus spp S.aureus CNS Streptococcus spp VGS S.bovis Other streptococci Enterococcus spp Culture negative Other (HACEK) 17 (38%)* 13 (29%)* 4 (9%)* 16 (35%) 10 (22%) 2 (4%) 4 (9%) 2 (4%) 5 (11%) 7 (15%) 18 (58%)* 3 (10%)* 15 (48%)* 9 (29%) 5 (16%) -- 4 (13%) 2 (6%) -- 2 (6%) 35 (46%) 16 (21%) 19 (25%) 25 (33%) 15 (20%) 2 (3%) 8 (10%) 4 (5%) 5 (6%) 9 (12%) NVE vs PVE groups (p<0.05)

  27. Echocardiography Diagnostic yield of TTE and TEE

  28. Native N=45 Prosthetic N=31 Total N=76 Echo findings Patients with vegetations Mean maximal veg. size (mm) Vegetations > 10 mm Patients with abscess Mean maximal abscess diameter Abscess > 10 mm Ventricular septal defect Mean EF (%) Mean LVEDD (mm) Multivalvular infection 96 %* 11.5 49 % 71 % 10 mm 44 % 21 % 62.5 55.2 33 % 65 %* 12.1 70 % 87 % 15 mm 67 % 19 % 60.5 54.4 26% 83 % 11.7 56 % 78 % 12 mm 54 % 20 % 61.7 54.9 30 % *Native vs prosthetic, p < 0.05

  29. Fistulized sinus of Valsalva (SV) Right SV Left SV Non coronary SV Fistulized cardiac chamber (%) Right atrium Right ventricle Left atrium Left ventricle Multiple Moderate/severe regurgitation Native N=45 Prosthetic N=31 Total N=76 Echo findings 44% 35% 20% 18% 31% 22% 13% 11% 64%* 26% 42% 32% 16% 16% 32% 19% 13%* 26%* 37% 38% 25% 17% 25% 26% 16% 12% 49% * Native vs prosthetic, p < 0.05

  30. Surgical treatment Time to surgery < 24 hours 2 - 7 days > 7 days Closure of fistula (%) Simple Pericardial patch Gore-tex patch Valve replacement Bioprosthesis Mechanical Homograft Native N=45 Prosthetic N=31 Total N=76 87% 33% 36% 31% 41% 46% 13% 95% 28% 49% 18% 87% 11% 52% 37% 41% 52% 7% 89% 19% 52% 19% 87% 24% 42% 34% 41% 48% 11% 92% 24% 50% 18%

  31. In-hospital mortality - Surgical group (N=66) - Medical group (N=10) Native N=45 Prosthetic N=31 Total N=76 16 (36%) 13/39 (33%) 3/6 (50%) 15 (48%) 15/27 (55%) 0/4 (-) 31 (41%) 28 (42%) 3 (30%) Medical N=3 Surgical N=28 Cause of death - Multiorgan failure - Sudden death - Septic shock - Cardiogenic shock - Hemorrhage 33% 33% - 33% - 23% 10% 26% 19% 23%

  32. Lost for follow-up Follow-up (mo., mean, range) Residual fistula Late CHF Late valvular replacement Late death Medical * N=7 Surgical N=38 2 4 36 (1-96)* - 3 0 1 29 (1-144)* 5 (11%) 7 (16%) 5 (11%) 3 ( 7%) * The 3 patients who died w/o surgery had fatal co-morbid conditions. The remaining 7 patients did not undergo surgery because they did not have cardiac failure, severe valvular regurgitation and echocardiographical abscess.

  33. Age > 65years Male gender Prosthetic endocarditis Symtoms duration >30 d. Moderate or severe CHF Renal failure Neurologic symptoms S.aureus infection Vegetation >10 mm Patients with periannular abscess Periannular abscess > 10 mm Moderate or severe AR Fistulized sinus of Valsalva Fistulized cardiac chamber EF <65% Urgent or emergency surgery OR – 95%CI p 2.8 (1.0-7.9) 0.8 (0.2-2.4) 2.5 (0.9-6.8) 0.8 (0.2-2.6) 2.2 (0.7-5.1) 1.8 (0.7-5.1) 0.6 (0.1-2.8) 1.2 (0.4-3.6) 1.2 (0.4-3.6) 1.6 (0.5-5.5) 2.3 (0.7-7.3) 0.8 (0.3-2.1) - - 1.1 (0.4-3.1) 2.7 (0.9-7.8) 0.05 0.6 0.07 0.7 0.15 0.2 0.5 0.8 0.7 0.4 0.14 0.7 0.9 0.2 0.8 0.06

  34. Limitations * Ascertainment bias – multicenter nature * Severity of CHF higher – low-grade shunts underdiagnosed * High-risk profles of surgical candidate * Not comparable to medically treated * Not comparing medical and surgical patients

  35. Abscesses vs fistulae

  36. Kaplan-Meier estimation of survival from time of diagnosis of periannular complication.

  37. Actuarial freedom from death, heart failure requiring hospital admission and repeat surgery in patients with periannular complications surviving the index hospitalization. A. patients referred to surgical therapy

  38. B. patients medically-managed

  39. * Aorto-cavitary fistulization in IE is an unfrequent event and occurs in patients with aortic endocarditis with high grade of local tissue destruction. * It was associated with staphylococci and streptococci native-valve IE and with coagulase-negative staphylococci prosthetic valve IE. * In-hospital mortality was high even when most patients were referred to surgical treatment. * Congestive heart failure identified the subgroup of patients with the worst prognosis. Conclusions

  40. Prosthetic valve endocarditis • What? • When? • Who? • Why?

  41. Methods * International Collaboration on Endocarditis Merged Database * Large, multicenter, international registry of patients with definite endocarditis by Duke criteria * Clinical, microbiological, echocardiographic variables to determine * Those factors associated with the use of surgery in PVIE * Logistic regression analysis * Propensity score to match surgery vs medical therapy

  42. PVIE – Patient characteristics

  43. Complications and outcomes of patients with PVIE

  44. Propensity analysis of surgical treatment of PVIE

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