1. Insuffisance mitrale organique Cas clinique mis à disposition par Claire BOULETI

2. Mitral Regurgitation (Iung et al. Eur Heart J 2003;24:1244-53) (Nkomo et al. Lancet 2006;368:1005-11) Euro Heart Survey Population-Based Series

3. Case study: Mitral regurgitation (MR) 52 years old man, no medical history, no CV risk factors Follow-up for degenerative MR since1995 Asymptomatic Clinical examination: BP 150/80 HR 66/min –Systolic heart murmur (3/6), heard at the apex (maximal), radiates to left side of the sternum and to the axilla. –No other abnormalities Chest x-rays: no LV enlargement, no fluid accumulation in the lungs. ECG: Sinus rhythm 66/min. No abnormalities

4. TTE

6. Echocardiogram results Mitral regurgitation Internal P2 prolapse Severe MR: Regurgitant volume 98 ml/beat ERO: 0,5 cm² LV 56/32 mm Preserved LV function LA dilation at 130 ml sPAP 36 mmHg

7. Stress Echocardiography Maximal stage of exercise tolerance test reached (96% of TMHB, 150W). Stress test stopped for muscular exhaustion. Asymptomatic patient Maximal stress sPAP: 50 mmHg

8. Novembre 2010 52 years old man, no comorbidity Severe degenerative MR, Truely symptomatic, No impact on LV function But LA dilation. How to manage this patient?

9. Management of asymptomatic MR Natural history Quantification Mechanisms Anatomy (segmental analysis) Guidelines

10. Natural History of MR Years Survival (%) Observed 57% Expected P = 0.016 65% (Avierinos et al. Circulation 2002;106:1355-61) Primary predictors EF ≤ 50% MR ≥ moderate Excess Mortality

11. Quantification of MR and Prognosis (Enriquez-Sarano et al. N Engl J Med 2005;352:875-83) Cardiac Deaths Cardiac Events 456 asymptomatic patients Quantification of the degree of MR Outcome under Medical Management

12. Criteria Mitral Regurgitation Specific signs of severe regurgitation Vena contracta width  0.7 cm with large central MR jet (area > 40% of LA) or with a wall impinging jet of any size, swirling in LA Large flow convergence Systolic reversal in pulmonary veins prominent flail mitral valve or ruptured papillary muscle Supportive signsDense, triangular CW Doppler MR jet E-wave dominant mitral inflow (E > 1.2m/s) Enlarged LV and LA size (particularly when normal LV function is present) Quantitative parameters Reg. Vol (ml/beat)  60 RF (%)  50 ERO (cm²)  0.40 (Adapted from Zoghbi et al. J Am Soc Echocardiogr 2003;16:777-802) Definition of Severe Mitral Regurgitation

13. Mechanism of MR Functional Classification (Carpentier) Etiology Feasability of repair

14. Etiology of MR Infective endocarditis Repair is feasible in experienced hands Rheumatic MR Less good late results (Deloche et al. J Thorac Cardiovasc Surg 1990; 99:990-1002)

15. Etiology of MR Degenerative MR  Repair is frequently feasible  Valve prolapse is the main mechanism  Wide spectrum of anatomic presentations Does anatomy influence the quality of late results ? Lesions Chordae : rupture, lenghtening Leaflets : thin or tissue excess, pliable Annular dilatation

16. (Monin et al. J Am Coll Cardiol 2005;46:302-9) Functional Analysis of MR 279 patients operated on for severe MR Valve repair: 237, valve replacement: 42 Good concordance between TTE and surgical findings Prognostic impact

17. Functional Analysis of MR Using 3D-Echo (La Canna et al. Am J Cardiol 2011;107:1365-74)

18. Class Asymptomatic patients with LV dysfunction (ESD > 45 mm* and /or LV EF  60%) IC Asymptomatic patients with preserved LV function and AF or pulmonary hypertension (sPAP >50 mmHg at rest) IIaC Asymptomatic patients with preserved LV function, high likelihood of durable repair, and low risk for surgery IIbB * Lower values can be considered for patients of small stature. Guidelines: Indications for Surgery in Severe Chronic Asymptomatic Organic Mitral Regurgitation

19. Class Asymptomatic patients with LV dysfunction (ESD > 45 mm* and /or LV EF  60%) IC Asymptomatic patients with preserved LV function and AF or pulmonary hypertension (sPAP >50 mmHg at rest) IIaC Asymptomatic patients with preserved LV function, high likelihood of durable repair, and low risk for surgery IIbB * Lower values can be considered for patients of small stature. Guidelines: Indications for Surgery in Severe Chronic Asymptomatic Organic Mitral Regurgitation

20. Septembre 2011 Asymptomatic Follow-up of its MR Clinical examination: unchanged

22. Septembre 2011 Asymptomatic Follow-up of its MR Clinical examination: unchanged TTE/TEE: severe MR, ERO= 50 mm 2 P2 posterior leaflet prolapse and tendinous cord rupture on degenerative mitral valve VG 66/45 mm LVEF > 60% LA Dilation: 130 ml sPAP: 35 mmHg Management of the patient?

23. In favor of MR treatment Natural history of MR due to flail leaflets Early LV dysfunction: ESD 45 mm Class Asymptomatic patients with LV dysfunction (ESD > 45 mm* and /or LV EF  60%) IC Asymptomatic patients with preserved LV function and AF or pulmonary hypertension (sPAP >50 mmHg at rest) IIaC Asymptomatic patients with preserved LV function, high likelihood of durable repair, and low risk for surgery IIbB * Lower values can be considered for patients of small stature.

24. In favor of MR treatment Natural history of MR due to flail leaflets Early LV dysfunction: ESD 45 mm Class Asymptomatic patients with LV dysfunction (ESD > 45 mm* and /or LV EF  60%) IC Asymptomatic patients with preserved LV function and AF or pulmonary hypertension (sPAP >50 mmHg at rest) IIaC Asymptomatic patients with preserved LV function, high likelihood of durable repair, and low risk for surgery IIbB * Lower values can be considered for patients of small stature.

25. (Enriquez-Sarano et al. Circulation 1994;90:830-7) > 60 % 409 patients undergoing MR surgery Facteurs prédictifsp FEVG0.0004 Age0.003 Créatinine0.006 Coronaropathie0.024 HTA0.016 Do not wait for LVEF < 60%

26. Treatment of degenerative MR Medical treatment: no option Mitral valve repair or MVR

27. (Mohty et al. Circulation 2001;104(suppl.I):I-1-7) Mitral valve repair or valve replacement? Long-term Results (Hammermeister et al. J Am Coll Cardiol 2000;36:1152)

28. Valve Repair is the Treatment of Choice (Enriquez-Sarano et al. Circulation 1995:1022-8)

29. Results of Surgery in Patients with Severe Mitral Regurgitation in NHYA Class I-II nValve Repair (%) Degenerative origin (%) Operative mortality (%) Maximum FU (years) Late survival (%) Tribouilloy19979 0.61080 Sousa Uva17599731598 Garbarz109100801787

30. www.escardio.org

31. Management of Asymptomatic Severe Chronic Organic Mitral Regurgitation LVEF > 60% and LVESD < 45 mm NoYes Atrial fibrillation or sPAP > 50 mmHg at rest NoYes * valve repair can be considered when there is a high likelihood of durable valve repair at a low risk Surgery (repair whenever possible) Follow-up* Severe asymptomatic organic MR

32. Management of Asymptomatic Severe Chronic Organic Mitral Regurgitation LVEF > 60% and LVESD < 45 mm NoYes Atrial fibrillation or sPAP > 50 mmHg at rest NoYes * valve repair can be considered when there is a high likelihood of durable valve repair at a low risk Surgery (repair whenever possible) Follow-up* Severe asymptomatic organic MR

33. Management of Symptomatic Severe Chronic Organic Mitral Regurgitation LVEF > 30% No Yes Valve repair is likely and low comorbidity NoYes * valve replacement can be considered in selected patients Surgery (repair whenever possible) Medical therapy* Transplantation Refractory to medical therapy YesNo Medical therapy Severe symptomatic organic MR

34. Class Symptomatic patients with LV EF >30% and ESD < 55 mm*IB Asymptomatic patients with LV dysfunction (ESD > 45 mm* and /or LV EF  60%) IC Asymptomatic patients with preserved LV function and AF or pulmonary hypertension (sPAP >50 mmHg at rest) IIaC Patients with severe LV dysfunction (LV EF 55 mm*) refractory to medical therapy with high likelihood of durable repair and low comorbidity IIaC Asymptomatic patients with preserved LV function, high likelihood of durable repair, and low risk for surgery IIbB Patients with severe LV dysfunction (LV EF 55 mm*) refractory to medical therapy with low likelihood of repair and low comorbidity IIbC * * Lower values can be considered for patients of small stature. Indications for Surgery in Severe Chronic Organic Mitral Regurgitation

35. Percutaneous Mitral Valve Repair ? Edge-to-Edge Technique: Mitraclip Everest IIRandomizedn=279 (Mitraclip 184/ Surgery 95)

36. EVEREST II Randomized Clinical Trial 279 Patients enrolled at 37 sites Randomized 2:1 Control Group Surgical Repair or Replacement N=95 Significant MR (3+-4+) Device Group MitraClip System N=184 MR etiology: Degenerative/functional (%): 73/27 in both groups (p=0.81)

37. Safety Major Adverse Events 30 days Effectiveness Clinical Success Rate * 12 months EVEREST II Device Group, n=180 Control Group, n=94 Met superiority hypothesis Pre-specified margin =2% Observed difference = 32.9% Control Group, n=89 Device Group, n=175 Met non-inferiority hypothesis Pre-specified margin = 25% Observed difference = 7.3% 66.9% 74.2% 15.0% 47.9% p SUP <0.0001p NI =0.0005 * Freedom from the combined outcome of death, MV surgery or re- operation for MV dysfunction >90 days post Index procedure, MR >2+ at 12 months

38. Safety Major Adverse Events 30 days Effectiveness Clinical Success Rate * 12 months EVEREST II Device Group, n=180 Control Group, n=94 Met superiority hypothesis Pre-specified margin =2% Observed difference = 32.9% Control Group, n=89 Device Group, n=175 Met non-inferiority hypothesis Pre-specified margin = 25% Observed difference = 7.3% 66.9% 74.2% 15.0% 47.9% p SUP <0.0001p NI =0.0005 * Freedom from the combined outcome of death, MV surgery or re- operation for MV dysfunction >90 days post Index procedure, MR >2+ at 12 months

39. Safety Major Adverse Events 30 days Effectiveness Clinical Success Rate * 12 months EVEREST II Device Group, n=180 Control Group, n=94 Met superiority hypothesis Pre-specified margin =2% Observed difference = 32.9% Control Group, n=89 Device Group, n=175 Met non-inferiority hypothesis Pre-specified margin = 25% Observed difference = 7.3% 66.9% 74.2% 15.0% 47.9% p SUP <0.0001p NI =0.0005 * Freedom from the combined outcome of death, MV surgery or re- operation for MV dysfunction >90 days post Index procedure, MR >2+ at 12 months MAE : All transfusions ≥ 2 Units

40. EVEREST II : MR Reduction Device GroupControl Group ≤2+ n=137n=119n=80n=67 3+/4+ ≤2+ 3+/4+ 81.5% 18.5% 3+/4+ 97.0%

41. Feasible Can be safely performed in experienced hands Can decrease the severity of MR at mid-term BUT No long-term results Only 1 randomized trial: 1-year results, residual MR in 18%. Very good results of mitral valve repair. for patients with contra-indications to or at high risk for surgery Waiting for thorough evaluation of results (randomized trials, long-term FU)

42. Back to Mr G Mitral valve repair P2 prolapse Repair of 2 cords on A2 And of 4 cords on P2, Surgical repair of incision between P2 and P3, Annuloplasty with implantation of a Duran flexible ring n°35 Per-operatory TEE: no prolapsus, negligible central MR

43. Results Favourable immediate evolution Post-operative echocardiography at D13 (TTE+TEE) No residual MR Mean gradient 4 mmHg LV 52/34 mm LVEF 65% At 3 months: Asymptomatic + normal examination/TTE

44. Post-operative TTE

46. MR is the 2nd most frequent valvular disease. Mainly of degenerative origin and the most frequent mechanism is valve prolapse. TTE is the key exam to assess MR mechanism, severity and anatomy (impact on the feasibility of valve repair). The prognosis of MR depends on LV function, which is not a reliable criterion for indicating surgery: do not wait for LVEF<60%. Conclusion (I)

47. There is a trend towards earlier interventions, but which needs to take into account the operative risk and the feasibility of valve repair. Intervention can be considered in asymptomatic patients without waiting for ESD > 45 mm or LVEF < 60%, provided: MR is severe Operative risk is low There is a high likelihood of durable valve repair (IIB) In other cases, “watchful waiting” is a valid alternative, with directing patients to surgery in case of early signs of LV dysfunction. Conclusion (II)