Suivi à long terme du TAVI: quelles leçons en 8rer? Dr Claire Boule, 17 Janvier 2015

Size: px

Start display at page:

Download "Suivi à long terme du TAVI: quelles leçons en 8rer? Dr Claire Boule, 17 Janvier 2015"

Gwen Bryan
5 years ago
Views:

1 Suivi à long terme du TAVI: quelles leçons en 8rer? Dr Claire Boule, 17 Janvier 2015

2 Disclosures Research grants from: SFC, FFC, FRM, Servier Lectures: Novar,s, Daichii Sankyo

3 Follow-up after TAVI Randomized trials Unbiased comparison with other treatments Mid-term follow-up (1 to 3 years) Observational series (registries) Not valid for comparisons No selection bias Longer follow-up

4 Randomized studies Circula(on October 21, 2014

5 Population 358 patients ( ) Variables TAVI n=179 Standard therapy n=179 Age, yr. 83 ± 9 83 ± Male sex 82 (46) 84 (47) 0.92 NYHA func,onal class 0.68 II III IV 14 (8) 165 (92) 11 (6) 168 (94) Atrial fibrilla,on 28/85 (33) 39/80 (49) 0.04 STS score (%) 11 ± 6 12 ± Logis,c EuroSCORE (%) 26 ± ± Frailty 21/116 (18) 33/118 (28) 0.09 Valve area (echocardiography), cm ± ± Mean gradient (Doppler), mmhg 45 ± ± Mean LVEF (%) 54 ± ± MR 3 38/171 (22) 38/165 (23) 0.90 p

6 Population 358 patients ( ) Variables TAVI n=179 Standard therapy n=179 Age, yr. 83 ± 9 83 ± Male sex 82 (46) 84 (47) 0.92 NYHA func,onal class 0.68 II III IV 14 (8) 165 (92) 11 (6) 168 (94) Atrial fibrilla,on 28/85 (33) 39/80 (49) 0.04 STS score (%) 11 ± 6 12 ± Logis,c EuroSCORE (%) 26 ± ± Frailty 21/116 (18) 33/118 (28) 0.09 Valve area (echocardiography), cm ± ± Mean gradient (Doppler), mmhg 45 ± ± Mean LVEF (%) 54 ± ± MR 3 38/171 (22) 38/165 (23) 0.90 p

7 Population 358 patients ( ) Variables TAVI n=179 Standard therapy n=179 Age, yr. 83 ± 9 83 ± Male sex 82 (46) 84 (47) 0.92 NYHA func,onal class 0.68 II III IV 14 (8) 165 (92) 11 (6) 168 (94) Atrial fibrilla,on 28/85 (33) 39/80 (49) 0.04 STS score (%) 11 ± 6 12 ± Logis,c EuroSCORE (%) 26 ± ± Frailty 21/116 (18) 33/118 (28) 0.09 Valve area (echocardiography), cm ± ± Mean gradient (Doppler), mmhg 45 ± ± Mean LVEF (%) 54 ± ± MR 3 38/171 (22) 38/165 (23) 0.90 p

8 Procedures SAPIEN heart valve system Common femoral artery access Under general anaesthesia

9 3-year mortality rate Circula(on October 21, 2014

10 Functional status NYHA class Circula(on October 21, 2014

11 Functional status Circula(on October 21, 2014

12 Randomized studies n engl j med 366;18 nejm.org may 3, 2012

13 Population 699 patients ( ) Variables TAVI N=348 Surgery N=351 Age, yr. 84 ± 7 85 ± Male sex 201 (58) 198 (57) 0.82 NYHA func,onal class II III IV 20 (6) 145 (42) 183 (52) 21 (6) 151 (43) 177 (51) Atrial fibrilla,on 81/199 (41) 75/172 (44) 0.60 STS score (%) 12 ± 3 12 ± Logis,c EuroSCORE (%) 29 ± ± Frailty 46/295 (16) 53/301 (18) 0.58 Valve area (echocardiography), cm ± ± Mean gradient (Doppler), mmhg 43 ± ± Mean LVEF (%) 53 ± ± MR 3 66/337 (20) 71/338 (21) 0.70 p NS

14 Population 699 patients ( ) Variables TAVI N=348 Surgery N=351 Age, yr. 84 ± 7 85 ± Male sex 201 (58) 198 (57) 0.82 NYHA func,onal class II III IV 20 (6) 145 (42) 183 (52) 21 (6) 151 (43) 177 (51) Atrial fibrilla,on 81/199 (41) 75/172 (44) 0.60 STS score (%) 12 ± 3 12 ± Logis,c EuroSCORE (%) 29 ± ± Frailty 46/295 (16) 53/301 (18) 0.58 Valve area (echocardiography), cm ± ± Mean gradient (Doppler), mmhg 43 ± ± Mean LVEF (%) 53 ± ± MR 3 66/337 (20) 71/338 (21) 0.70 p NS

15 Procedures TAVR: 244 pa,ents with transfemoral access 104 with transapical approach SAPIEN Valve Under general aneathesia SAVR: 351 pts

16 All cause mortality n engl j med 366;18 nejm.org may 3, 2012

17 All cause mortality n engl j med 366;18 nejm.org may 3, 2012

18 CoreValve US Pivotal Trial Adams et al. N Engl J Med 2014

19 Study design Adams et al. N Engl J Med 2014

20 Study design Adams et al. N Engl J Med 2014

21 Population 747 patients (Feb 2011-Sept 2012)

22 Procedures CoreValve (self-expandable) Transfemoral (n=323) Subclavian (n=67) Direct Aortic

23 1-year mortality Adams et al. N Engl J Med 2014

24 Indications for TAVI TAVI should only be undertaken with a multidisciplinary heart team including cardiologists and cardiac surgeons and other specialists if necessary. Class I Level C TAVI should only be performed in hospitals with cardiac surgery on-site. I C TAVI is indicated in patients with severe symptomatic AS who are not suitable for AVR as assessed by a heart team and who are likely to gain improvement in their quality of life and to have a life expectancy of more than 1 year after consideration of their comorbidities. TAVI should be considered in high risk patients with severe symptomatic AS who may still be suitable for surgery, but in whom TAVI is favoured by a heart team based on the individual risk profile and anatomic suitability. I IIa B B European Heart Journal 2012 & European Journal of Cardio-Thoracic Surgery 2012

25 Indications for TAVI TAVI should only be undertaken with a multidisciplinary heart team including cardiologists and cardiac surgeons and other specialists if necessary. Class I Level C TAVI should only be performed in hospitals with cardiac surgery on-site. I C TAVI is indicated in patients with severe symptomatic AS who are not suitable for AVR as assessed by a heart team and who are likely to gain improvement in their quality of life and to have a life expectancy of more than 1 year after consideration of their comorbidities. TAVI should be considered in high risk patients with severe symptomatic AS who may still be suitable for surgery, but in whom TAVI is favoured by a heart team based on the individual risk profile and anatomic suitability. I IIa B B European Heart Journal 2012 & European Journal of Cardio-Thoracic Surgery 2012

26 Management of severe AS No LVEF < 50% Severe AS Symptoms Yes No Yes Contraindication for AVR No Physically active No Yes Exercise test Symptoms or fall in blood pressure below baseline Yes No High risk for AVR No Yes Yes Short life expectancy No Yes Presence of risk factors and low/intermediate individual surgical risk TAVI Med Rx No Yes AVR Re-evaluate in 6 months AVR or TAVI European Heart Journal 2012 & European Journal of Cardio-Thoracic Surgery 2012

27 TAVI: long-term follow-up N= Years Follow- up (years) Canadian Registry Toggweiler Bichat

28 Canadian Registry Rodès- cabau et al, JACC 2012

29 Population 339 patients (January June 2009) Variables All N=339 Transfemoral N=162 Transapical N=177 Age, yr. 81 ± 8 83 ± 8 80 ± Male sex 152 (45) 91 (56) 61 (35) < NYHA func,onal class II III - IV 29 (9) 308 (91) Crea,nine clearance 119 ± 83 NS Atrial fibrilla,on 115 (34) 66 (41) 49 (28) Peripheral vascular disease 120 (36) 31 (19) 89 (50) < COPD 100 (30) NS STS score (%) 10 ± 6 9 ± 6 11 ± Frailty 85 (25) NS Severe MR 27 (8) 18 (11) 9 (5) Mean LVEF (%) 55 ± 14 NS p NS Rodès- cabau et al, JACC 2012

30 30-day outcome and follow-up Use of SAPIEN valves Successful procedure 322 (94.9) Complica,ons: Stroke 8 (2.3) Need for permanent pacemaker implanta,on 17 (4.9) Conversion to open heart surgery 6 (1.7) Death 36 (10.6) FU in 99.1% of the study popula,on Mean follow- up of 42 ± 15 months

31 Overall survival at 4 years Rodès- cabau et al, JACC 2012

32 Causes of death

33 Causes of death

34 Predictive factors of late deaths Rodès- cabau et al, JACC 2012

35 Canadian Registry: conclusion Pa,ents with COPD, CKD, frailty, and chronic AF were at higher risk of death within the few years ajer TAVI, sugges,ng that a more careful evalua,on and follow- up of pa,ents with these comorbidi,es might translate into beker mid- to long- term outcomes.

36 5-year follow-up Toggweiler et al, JACC 2013

37 Study design SAPIEN valve Transfemoral in 64 pa,ents (73%) Transapical in 24 pa,ents (27%)

38 Study design SAPIEN valve Transfemoral in 64 pa,ents (73%) Transapical in 24 pa,ents (27%) Toggweiler et al, JACC 2013

39 Population 88 pts (January 2005-March 2007)

40 5-year survival after successful TAVI

41 Predictive factors of late deaths In mul,variable analysis, - chronic obstruc,ve pulmonary disease (HR: 2.17; 95% CI: 1.18, 3.70) - at least moderate paravalvular regurgita,on post- TAVI (HR: 2.98; 95% CI: 1.44, 6.17)

42 Toggweiler et al, JACC 2013 Good long-term valve function At 5 years, 3 pa,ents had moderate prosthe,c valve failure. None of the pa,ents had severe regurgita,on or stenosis, and no pa,ent required reopera,on or reinterven,on due to structural valve failure.

43 6-year follow-up Long- term outcome awer TAVI Claire Boule,, Dominique Himbert, Bernard Iung, Benjamin Alos, Caroline Kerneis, Walid Ghodbane, David Messika- Zeitoun, Eric Brochet, Amir- Ali Fassa, Jean- Pol Depoix, Phalla Ou, Patrick Nataf, Alec Vahanian Boule, et al, Heart 2015, in press

44 Study design prospec8ve single- center registry 141 consecu,ve pa,ents underwent TAVI SAPIEN valve (90%) Transfemoral in 84 pa,ents (68%) Transapical in 37 pa,ents (30%) 18 pa,ents died within 30 days 123 pa,ents in study Boule, et al, Heart 2015, in press

Population 123 patients (Oct 2006- Dec 2009) Variables n= 123 Age 82 ± 8 Male Sex 69 (56) Lower limb arteri,s 18 (15) Chronic Lung Disease 36 (29) LVEF 50 ± 13 Indexed aor,c valve area 0.4 ± 0.

45 Population 123 patients (Oct Dec 2009) Variables n= 123 Age 82 ± 8 Male Sex 69 (56) Lower limb arteri,s 18 (15) Chronic Lung Disease 36 (29) LVEF 50 ± 13 Indexed aor,c valve area 0.4 ± 0.1 Mitral regurgita,on 2/4 21 (17) Atrial fibrilla,on 51 (42) Systolic PAP 47 ± 15 Charlson Comorbidity Index 5 ± 2 STS score 7 ± 5 Euroscore I 22 ± 12 NYHA Class 88% of pa,ents in NYHA class III or IV

46 Follow-up and events FU was complete in 122 pa,ents (99%). Median FU was 3.6 years [ ], and maximum reached 6 years. Events during FU: death, NYHA III or IV, stroke, severe bleeding and cardiac hospitalisa,on according to VARC- 2 criteria. 2 endpoints (1) overall survival (2) event- free survival (VARC- 2 criteria)

47 Events during FU Events Pa8ents N=123 Severe bleeding 9 (7) Stroke 16 (13) Infec,ve endocardi,s 3 (3) Pace- Maker implanta,on 18 (15) Re- hospitaliza,on Cardiac Non- cardiac Death Cardiac Non Cardiac Unknown 96 (78) 42 (44) 54 (56) 77 (63) 25 (33) 44 (57) 8 (10) NYHA III- IV at last FU 40 (33)

48 6-year overall survival rate after successful TAVI

49 Predictive factors of late death Mul,variate analysis Adjusted Hazard Ratio [95% CI] p Lower limb arteritis 2.18 [ ] Charlson comorbidity index (per 1-unit increase) 1.12 [ ] Paraprosthetic AR! 2/4 at day [ ] 0.010!

50 Events during FU Events Pa8ents N=123 Severe bleeding 9 Stroke 16 (13) Infec,ve endocardi,s 3 (3) Pace- Maker implanta,on 18 (15) Re- hospitaliza,on Cardiac Non- cardiac Death Cardiac Non Cardiac Unknown 96 (78) 42 (44) 54 (56) 77 (63) 25 (33) 44 (57) 8 (10) NYHA III- IV at last FU 40 (33)

51 Events during FU Events Pa8ents N=123 Severe bleeding 9 Stroke 16 (13) Infec,ve endocardi,s 3 (3) Pace- Maker implanta,on 18 (15) Re- hospitaliza,on Cardiac Non- cardiac 96 (78) 42 (44) 54 (56) CoreValve prosthesis (HR 95% CI 4.0 [ ] p=0.016) Death Cardiac Non Cardiac Unknown 77 (63) 25 (33) 44 (57) 8 (10) NYHA III- IV at last FU 40 (33)

52 Events during FU Events Pa8ents N=123 Severe bleeding 9 Stroke 16 (13) Infec,ve endocardi,s 3 (3) Pace- Maker implanta,on 18 (15) Re- hospitaliza,on Cardiac Non- cardiac Death Cardiac Non Cardiac Unknown 96 (78) 42 (44) 54 (56) 77 (63) 25 (33) 44 (57) 8 (10) NYHA III- IV at last FU 40 (33)

53 Stroke Boule, et al, Heart 2015, in press

54 Stroke Older age (HR 95% CI 1.2 [ ] p=0.003) Previous cerebrovascular accident (HR 95% CI 3.8 [ ] p=0.03) Higher crea,nine level (HR 95% CI 1.01 [ ] p=0.0001).

55 Event-free survival (VARC-2 Criteria) In mul,variate analysis, 2 predictors of late events: higher Charlson Comorbidity Index (p=0.01), and post- procedure PAR 2/4 (p=0.01)

56 Functional status The rate of good late func,onal results (survival in NYHA class I or II) was 32 ± 5% at 5 years Boule, et al, Heart 2015, in press

57 Quality of life EQ- 5D ques8onnaire and visual analogical scale of QoL in the 45 survivors Best state 76% had no problem with self- care 50% had no difficul,es in performing their usual ac,vi,es 50% were pain free 33% of pa,ents could walk easily 50% were neither anxious nor depressed. 64 ± 12 Worse state

58 Long-term survival Con,nuous akri,on of results More than half of deaths are related to non- cardiac causes N= Follow- up (years) Non cardiac death (%) Canadian Registry Toggweiler Bichat

59 Long-term FU after TAVI: which lessons? N= Follow- up (years) Predic8ve factors of late mortality Canadian Registry AF COPD crea,nin clearance Frailty Toggweiler 88 5 COPD AR post- TAVI Bichat Charlson Index Lower limb arteri,s AR post- TAVI Impact of : Comorbidi,es Post- TAVI AR

1%) using Sapien valve) Half of deaths were of non-cardiac cause Myocardial Infarc,on 6 (13.3%) Endocardi,s 3 (6.7%) Renal Failure 11 (12.

60 Weight of comorbidities ALL 179 Causes of death (30 days to 1 Year) Cardiac 45 (25.1%) Non Cardiac 88 (49.2%) Unknown 46 (25.7%) in the Source Registry 1038 patients (TAVI Heart Failure 28 (62.2%) Pulmonary*** 21 (23.9%) Sudden Death 18 (39.1%) using Sapien valve) Half of deaths were of non-cardiac cause Myocardial Infarc,on 6 (13.3%) Endocardi,s 3 (6.7%) Renal Failure 11 (12.5%) Cancer 10 (11.4%) Unknown 18 (39.1%) Other 10 (21.7%) (Thomas et al. Other* 8 (17.8%) Stroke 9 (10.2%) Circulation 2011;124:425-33) Gastrointes,nal 5 (5.6%) Other** 32 (36.4%)

Weight of comorbidities ALL 179 Causes of death (30 days to 1 Year) Cardiac 45 (25.1%) Non Cardiac 88 (49.2%) Unknown 46 (25.7%) in the Source Registry 1038 patients (TAVI Heart Failure 28 (62.

61 Weight of comorbidities ALL 179 Causes of death (30 days to 1 Year) Cardiac 45 (25.1%) Non Cardiac 88 (49.2%) Unknown 46 (25.7%) in the Source Registry 1038 patients (TAVI Heart Failure 28 (62.2%) Pulmonary*** 21 (23.9%) Sudden Death 18 (39.1%) using Sapien valve) Half of deaths were of non-cardiac cause Myocardial Infarc,on 6 (13.3%) Endocardi,s 3 (6.7%) Renal Failure 11 (12.5%) Cancer 10 (11.4%) Unknown 18 (39.1%) Other 10 (21.7%) (Thomas et al. Other* 8 (17.8%) Stroke 9 (10.2%) Circulation 2011;124:425-33) Gastrointes,nal 5 (5.6%) Other** 32 (36.4%)

62 Weight of comorbidities Mortality accorging to the STS score PARTNER B, 2014

63 Weight of comorbidities Mortality accorging to the Logistic ES Moat et al, JACC Vol. 58, No. 20, 2011

64 Weight of comorbidities The Charlson Comorbidity Index Non- modifiable factor but shoud be given par,cular considera,on in the analysis by the Heart Team Charlson Index > 5 associated with poor late prognosis ajer TAVI

Weight of comorbidities: Frailty 5- year follow- up 6- year follow- up No evalua,on of frailty 4- year follow- up = Frailty was defined as a syndrome of decreased reserve and resistance

65 Weight of comorbidities: Frailty 5- year follow- up 6- year follow- up No evalua,on of frailty 4- year follow- up = Frailty was defined as a syndrome of decreased reserve and resistance to stressors, resul,ng from mul,ple declines across mul,ple physiologic systems leading to vulnerability to adverse outcomes. No systema8c tests were performed for the evalua8on of frailty

66 Frailty Prevalence in patients undergoing TAVI 25% in a multicentre Canadian series of 339 patients (Rodés-Cabau et al. J Am Coll Cardiol 2010;55: ) 17% in the TAVI German Registry (697 patients) (Zahn et al. Eur Heart J 2011, 32: ) 23% in the Partner B Cohort (358 patients) (Leon et al. N Engl J Med 2010;363: ) Impact of indices of functional performance / frailty - Indice de Katz - IADL

67 Impact of paravalvular leak Paraprosthe,c AR is the only post- procedural factor related to late survival in different long- term studies. But nega,ve impact for mild or moderate PAR?

68 Impact of paravalvular leak n engl j med 366;18 nejm.org may 3, 2012

69 Impact of paravalvular leak n engl j med 366;18 nejm.org may 3, 2012

70 Impact of paravalvular leak Toggweiler et al, JACC 2013

71 Impact of paravalvular leak PAR 2 is associated with poor late prognosis ajer TAVI

72 Impact of paravalvular leak

73 Conclusion (I) Due to randomized studies, in patients with severe symptomatic aortic stenosis who are at high risk for surgery - TAVI is now the reference treatment when surgery is contraindicated - When surgery is not contraindicated, TAVI is a valid alternative Longer follow- up in observa,onal studies provide encouraging informa,on on survival in pa,ents discharged alive ajer TAVI, and a sustained improvement in func,onal status. Sustained good valve func,on.

74 Conclusion (II) Predic,ve factors of late results underline the need for careful assessment of comorbidi,es and confirm the main impact of paraprosthe,c AR on long- term results. Poten,al Improvements?: Use of Charlson Index Use of systema,c tests for the evalua,on of frailty Use of post- dilata,on? New genera,on prosthesis to limit PAR

75 Merci de votre aken,on

Measuring the risk in valve patients Lessons learnt from the TAVI story? Bernard Iung Bichat Hospital, Paris, France

Measuring the risk in valve patients Lessons learnt from the TAVI story? Bernard Iung Bichat Hospital, Paris, France Faculty disclosure Bernard Iung I disclose the following financial relationships: Consultant