1. METAΛΛΙΚΗ ΠΡΟΣΘΕΤΙΚΗ ΒΑΛΒΙΔΑ-ΑΥΤΟΝΟΜΗ ΝΟΣΟΣ? Γ.ΔΡΟΣΟΣ Καρδιοχειρουργική Κλινική ΓΝΘ Γ. Παπανικολάου, Θεσσαλονίκη

2. Valve replacement since early 1960s improved outcome of pts with valvular heart disease 90 000 valve substitutes each year in US 280 000 worldwide each year Half mechanical, half bioprosthetic valves Despite improvements in prosthetic valve design and surgical procedures, valve replacement does not provide a definitive cure

3. Disease is a medical condition associated with specific symptoms and signs, caused by internal dysfunction or external factors that produce clinical impairment of normal function Native valve disease is traded for “prosthetic valve disease” ? Replacement of a diseased heart valve with a prosthetic valve exchanges the native disease for complications that are peculiar to the prosthesis. epidemiological and clinical features

4. PROSTHETIC VALVE DISEASE (long term complications) Valve thrombosis Systemic emboli Bleeding – anticoagulation related Structural Valve Degeneration Infection Hemolysis

5. Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations Acute or subacute presentation Thrombus formation, pannus ingrowth, or combination Pannus ingrowth (subvalvular annulus) in both bioprosthesis and mechanical Thrombus in mechanical valves due to inadequate antithrombotic therapy or in bioprosthetic valves in the early postop period 0.3-1.3% per pt-yr obstructive valve thrombosis in mechanical Raudart et al. Heart 2007;93:137–142

6. Ruel et al. Ann Thorac Surg 2004;78:77– 84 Late incidence and determinants of stroke after aortic and mitral valve replacement 20% of pts have an embolic stroke by 15 years after valve replacement Intracranial bleeding event 0.2-0.3% per pt yr RISK FACTORS age>75 yrs, female, smoking, CAD, AF with aortic prostheses mechanical type, advanced LV dysfunction with mitral prostheses * No effect of 3 months anticoagulation in bioprostheses No effect of aspirin adjunct

7. Anticoagulant-Related Hemorrhage annual risk of a hemorrhagic event is 1% per pt-yr more common with a mechanical due to excessive anticoagulation Structural Valve Degeneration Degenerative and atherosclerotic process- immune? Extremely rare with mechanical valves RISK FACTORS: younger age, mitral position, renal insufficiency, and hyperparathyroidism Hypertension, LV hypertrophy, poor LV function, and prosthesis size for the aortic position Most frequent cause of reoperation in bioprostheses rate of failure of 10% at 10 years in pts>70yrs and 20-30% in pts <40 yrs

8. Infective Endocarditis 0.1-2.3 % per pt-yr, even with appropriate antibiotic prophylaxis high mortality rates (30% to 50%) Risk for early PVE is higher (5%) when for active endocarditis Risk for late PVE is lower for mechanical than for bioprostheses BIO: 0.49% per pt year for MV and 0.91% for AV MECH: 0.18% per pt year for MV and 0.27% for AV Medical treatment : in late PVE and in nonstaphylococcal infections Surgery: failure of medical treatment; hemodynamically significant prosthesis regurgitation, especially if associated with deterioration of LV function; large vegetations; and development of intracardiac fistulas Piper et al. Heart 2001;85:590–593

9. Intravascular hemolysis in patients with new-generation prosthetic heart valves: A prospective study 434 pts 1997-1998, Italy Mild degrees of intravascular hemolysis common in normal functioning prostheses (50-95% of mechanical) 26% in these series Higher in double valve replacement mitral position Absence in stentless aortic bioprostheses Low incidence in stented aortic bioprostheses !!!TEE for early detection of subclinical periprosthetic leaks Mecozzi et al. J Thorac Cardiovasc Surg 2002;123:550-6

10. Bourguignon et al. The Journal of Heart Valve Disease 2011;20:673-680 Risk factors for valve-related complications after mechanical valve replacement in 505 pts with long-term follow up Carbomedics 505 pts 1988-2005, France Implantation in the mitral position Risk factors for bleeding unstable INR history of thromboembolic or bleeding events The use of antiplatelet agents proved to be a protective factor against thromboembolic events.

11. http://www.sts.org/sts-nationaldatabase/database-managers/adult-cardiac-surgery- database/adult-cardiacsurgery-database STS NATIONAL DATABASE – SAMPLE DATA 2009 AVR mechanical 14% bioprosthetic 85% Mean age 68.4 yrs 60yrs <50%< 79yrs 4.7% endocarditis – 70% elective Operative mortality 3% In-hospital mortality 2.6% Anticoagulation complications 1.7% MVR mechanical 34% bioprosthetic 65% Mean age 62.3 yrs 53yrs <50%< 73yrs 19% endocarditis – 59% elective Operative mortality 5% In-hospital mortality 4.7% Anticoagulation complications 2.4%

12. BIOLOGICAL VERSUS MECHANICAL Aortic or mitral position (worse survival in MVR) Isolated first time or double or reop Large series – retrospective / prospective Operating time frame (surgical and valve design evolution) Infective endocarditis (not appropriate to generalize – different baseline and evolution of disease)

13. Edinburgh Heart Valve Trial Veterans Affairs Cooperative Study on Valvular Heart Disease (Randomized trials) Different era of surgical technique Compared prosthetic valves that are no longer implanted

14. Hammermeister et al. J Am Coll Cardiol 2000;36:1152– 8 Outcomes 15 yrs after valve replacement with a mechanical vs a bioprosthetic valve: final report of the Veterans Affairs Randomized Trial Hancock vs Bjork-Shiley 575 pts 1977-1985 Colorado, Arizona, Illinois,California Mortality – lower for mech AVR (66% vs 79%, p < 0.02) Primary valve failure - in pts <65 yrs bio vs mech, 26% vs 0%, p<0.001 for AVR 44% vs 4%, p=0.0001 for MVR Reoperation - higher for bioprosthetic AVR (p =0.004) Bleeding - more frequently in pts with mechanical valve Thromboembolism - similar Valve-related complications - similar

15. Oxenham et al. Heart 2003;89:715–721 Twenty year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses No difference in survival Improved survival for mech with the original prosthesis intact after 8–10 yrs for MVR and 12–14 yrs for AVR Increased reoperation for porcine bioprosthesis Bleeding more common in mechanical No difference in thromboembolism and endocarditis Porcine bioprosthesis vs Bjork-Shiley 541 pts 1975-1979, Edinburgh

16. Khan et al. J Thorac Cardiovasc Surg 2001;122:257-69 Twenty-year comparison of tissue and mechanical valve replacement Hancock-Carpentier vs mech St Jude 2533 pts 1976-1992, California Multivariable analysis - type does not affect survival Analysis by age or CAD - similar long-term survival Risk of hemorrhage - higher only in mech AVR Thromboembolism rates - similar Reoperation rates - higher in tissue/ increase with time Valve complications - higher in mech AVR - cross over in tissue after 7yrs for MVR and 10yrs for AVR

17. AVR MVR Khan et al. J Thorac Cardiovasc Surg 2001;122:257-69

18. Lund et al. J Thorac Cardiovasc Surg 2006;132:20-6 Risk-corrected impact of mechanical vs bioprosthetic on long-term mortality after AVR Large metaanalysis in 17439 pts mechanical and biologic valve mean age (58 vs 69 yrs) mean follow-up (6.4 vs 5.3 years) CABG (16% vs 34%) endocarditis (7% vs 2%) death rate (3.99 vs 6.33 %/pt-year) Death rate corrected for age, NYHA class III and IV, and CABG left valve type with no effect.

19. Lund et al. J Thorac Cardiovasc Surg 2006;132:20-6 bioprosthetic valve series mean age of 71 to 74 years thromboembolism varied from 1.40% to 6.45% per pt-year. bleeding rates ranged from nearly nothing to 1.18%/pt-year Dogma that biological valves are not thrombogenic and do not require AC treatment BUT a bioprosthetic valve does not protect 1.from the “normal occurrence” of gastrointestinal, urogenital, and cerebral bleeding 2. from the “background rate” of stroke 3.from requiring oral AC treatment for the usual (nonprosthetic valve) indications, and more than 20% of pts have been reported to be taking oral warfarin at a mean of 2.6 to 5.8 years after AVR

20. Stassano et al. JACC 2009;54;1862-1868 AVR: a prospective randomized evaluation of mechanical vs biological valves in patients ages 55 to 70 yrs Carpentier vs St Jude-Carbomedics 310 pts 1995-2003, Italy No difference in the survival rate at 13 years Valve failure more frequent in bio (p=0.0001) Reoperation more frequent in bio (p=0.0003) Thromboembolism - similar Bleeding - similar Endocarditis - similar Valve-related complications - similar

22. Treatment of Endocarditis With Valve Replacement: The Question of Tissue Versus Mechanical Prosthesis 1964-1995 306 pts (209 NVE 97 PVE) Operative mortality 18% Survival 44±5% NVE 16±7% PVE at 20 yrs Moon et al. Ann Thorac Surg 2001;71:1164 –71)

23. Age <60 yrs Age >60 yrs For pts < 60yrs, overall long-term survival was similar in those who received a mechanical or a biologic valve

24. Age <60 yrs Age >60 yrs Moon et al. Ann Thorac Surg 2001;71:1164 –71) In younger patients, the long-term reoperation rate was higher with bioprosthetic valves than with mechanical, but, as patient age increased, the freedom from reoperation rates converged. Mechanical valves are more suitable for younger pts with NVE

25. Nguyen et al. European Journal of Cardio-thoracic Surgery 37 (2010) 1025—1032 AVR for active infective endocarditis: 5-year survival comparison of bioprostheses, homografts and mechanical prostheses 1998-2000 167 pts PROSPECTIVE STUDY

26. Nguyen et al. European Journal of Cardio-thoracic Surgery 37 (2010) 1025—1032 5 yr death rate hazard ratio

27. outcome affected by prosthetic valve hemodynamics, durability, and thrombogenicity BUT complications can be prevented or impact minimized by optimal prosthesis selection modifiable risk factors careful medical management after implantation careful follow-up after implantation Pibarot et al. Circulation 2009, 119:1034-1048

28. SELECTING PROSTHETIC VALVE 1.Patient’s age 2.Patient preference 3.Life expectancy increasing to 17 yrs for a 65-year- old white man in US mortality from chronic debilitating or fatal diseases in elderly long life span makes SVD almost inevitable in elderly 4.Contraindication for warfarin 5. Comorbidities

29. In favor of mechanical valve (1) preference of a mechanical valve, no warfarin contraindication (2) already on anticoagulation (3) at risk of accelerated SVD (young, hyperparathyroidism, renal insufficiency) (4) <65 yrs of age and long life expectancy In favor of bioprosthesis (1) preference of bioprosthesis (2) good-quality anticoagulation is unavailable (contraindication or high risk,compliance problems, lifestyle) (3) >65 yrs of age and/or limited life expectancy (4) woman of childbearing age