Percutaneous Transcatheter Treatment of Valvular Disease TAVR and Beyond

Transcription

1 Percutaneous Transcatheter Treatment of Valvular Disease TAVR and Beyond CREIGHTON W. DON, MD, PHD ASSOCIATE PROFESSOR OF MEDICINE DIRECTOR, INTERVENTIONAL AND STRUCTURAL HEART FELLOWSHIPS DIVISION OF CARDIOLOGY UNIVERSITY OF WASHINGTON

2 TAVR: PARTNER High Risk 5-year Mortality Outcomes Mack MJ. Lancet. 2015

3 PARTNER II: Intermediate Risk TF cohort Stroke Surgery TAVR 30 d 6.1% 5.5% 1 year 8.1% 8.0%

4 TAVR: PIVOTAL High Risk CoreValve New pacemaker 25.8%

5 Intermediate Risk--SURTAVI

6 Event Rate (%) All-cause Mortality at 30 Days RESPOND & Other Real World TAVI Registries Studies FRANCE 2 Registry 1 SAPIEN SOURCE 2 TVT Registry 3 SAPIEN XT SOURCE 4 CoreValve ADVANCE 5 LOTUS RESPOND 6 STS Score: 14.4 NA N: Results from different studies not directly comparable. Information provided for educational purpose only. 1 FRANCE:Gilard, et al. N Engl J Med 2012; 366: SOURCE : Thomas, et al. Circulation. 2010; 122: Mack, et al. JAMA 2013;310: SOURCE XT: Schymik, et al. JACC 2015; 8.5: CoreValve ADVANCE: Linke A, EuroPCR Lotus RESPOND: ACC Boston Scientific Corporation All Rights Reserved. For internal Educational Use only. Do not copy, forward or distribute.

7 Transcatheter aortic valve (TAVR)

8 Transcatheter aortic valve (TAVR)

9 TAVR: Next generation valves Portico Engager Symetis Direct Flow Jenavalve Boston Lotus

10 Where do we go from here? TAVR (native AS) will be nearly as ubiquitous as PCI Valve-in-valve, Extreme-risk TAVR, Aortic Regurgitation Mitral and tricuspid valve therapies

11 TAVR: Ongoing challenges VALVE IN VALVE, CORONARY OBSTRUCTION, EXTREME RISK PATIENTS

12 TAVR: Valve-in-Valve

13 TAVR: Valve-in-Valve

14 Valve-in-Valve 97 yo man with Medtronic 23 mm Hancock AV 4.1 m/s, 42 mmhg

15 Valve-in-Valve 23 Sapien XT

16 Dvir D. Circulation Dvir D. JAMA TAVR Valve-in-valve Global VIV registry 202 Patients with failed aortic bioprostheses (regurg/stenosis)

17 POST-TAVR Mean Gradient Courtesy John Webb, MD

18 TAVR: Valve-in-Valve Date AVA Mean grad Velocity 7/23/ mmhg 4.1 m/s 7/30/ mmhg 2.6 m/s 8/28/ mmhg 3.2 m/s 2/5/ mmhg 3.7 m/s 8/13/ mmhg 3.8 m/s

19 UW Experience 25 patients with valve-in-valve TAVR 3 patients with increasing gradients Goleski P, Don C. CCI 2016.

20 Valve-in-valve: Fracturing Bioprosthetic valve fracturing Saxon JT. Interventional Cardiology Review 2018;13(1):20 6.

21 Valve-in-valve: Fracturing Saxon JT. Interventional Cardiology Review 2018;13(1):20 6.

22 Valve-in-valve: Fracturing Saxon JT. Interventional Cardiology Review 2018;13(1):20 6.

23 Coronary Obstruction

24 BASILICA (Leaflet laceration/coronary obstruction) Khan, J.M. et al. J Am Coll Cardiol. Int. 2018

25 Valve-in-Valve RCA Coronary evaluation LCA

26 TAVR Exteme Risk 65 yo man with severe aortic stenosis in shock On IABP, dobutamine, phenylephrine, norepinephrine, vasopressin Acute renal failure Cr 3.1 Troponin 22 EF 20% Severe mitral regurgitation RA 17, PA 65/30, Wedge 25, CI 2.3 PAPI 2.0

27 Tandem Heart supported TAVR

28 Patient Selection: Emergent TAVR Cardiogenic shock/pressor dependent Cardiac arrest within 24 hrs Unstable ventricular arrhythmia Severe, unrelenting chest pain Mechanical circulatory support Decompensated heart failure requiring intubation

29 TAVR Extreme Risk Emergent/Shock TAVR PARTNER Cohort B 39% 44.1% 51% 33%

30 Survival by timing of MCS placement

31 The next best thing is coming here TRANSCATHETER MITRAL VALVE THERAPIES

32 Mitral Valvuloplasty

33 % Moderate to severe disease % Moderate to severe disease Epidemiology United States 1.7% of US population Olmstead County Nkomo VT. Et al. Lancet Sep 16;368(9540):

34 Heart Failure and Mitral Regurgitation Patients with chronic heart failure in 4 Italian Centers 73% of patients have FMR Rossi. Heart. 2011;97:

35 Mitral Valve Anatomy Degenerative Leaflets/chords/papillary Fibrotic/Calcified Leaflets/chords/annulus Functional Dilated ventricle/annulus Papillary muscle tethering Asgar AW et al. J Am Coll Cardiol Mar 31;65(12):

36 Percutaneous Valve Solutions MitraClip Percutaneous Valves TAVR in mitral Tiara (Neovasc), Tendyne, CardiAQ, Twelve

37 Percutaneous Annular Solutions Carillon (Cardiac Dimensions) Cardioband (Valtech) AccuCinch (Ancora Heart) Mitralign

38 Heart Failure and Mitral Regurgitation ATTEND registry (4842 patients) Moderate-Severe functional MR (at discharge) prevalence Preserved EF 18.4% Reduced EF 31.7% Kajimoto K et al. Eur J Heart Fail Aug;18(8):

39 Surgery for functional MR Retrospective propensity matched comparison Patients with severe MR and LVEF <30% Those undergoing MV compared to those medically managed Non-MVA MVA AHA/ACC 2017 Guideline Update Transcatheter mitral valve repair or mitral valve surgery for functional mitral insufficiency with a background of GDMT (IIB) Wu AH et al. J Am Coll Cardiol Feb 1;45(3):381-7.

40 MV surgery and CABG STITCH study Patients with severe mitral regurgitation MVR performed during CABG at operator s discretion CABG only 55 pts CABG/MVR 49 pts Rx 116 pts Grayburn D et al. Circulation (21)

41 Flail Mitral Regurgitation Surgery Mitral Regurgitation International Database ( ) 2097 patients with flail mitral valve leaflets Mean follow-up 10.3 years Suri RM. JAMA Aug 14;310(6):

42 Progression of MR and LV dysfunction 1 Cioffi G, et al. European Journal of Heart Failure 2005 Dec;7(7):1112-7

43 Mitral valve replacement

44 Tiara Mitral Regurgitation Clinical Trial High risk surgical patients with severe MR Cheung A at al. EuroIntervention. 2016;12;Y70-Y72.

45 TAVR in Mitral Stenosis/Regurg 71 year-old-man XRT germ cell tumor at age 35 Significant coronary artery disease and aortic regurgitation CABG and mechanical AVR at age 62 Known to have moderate mitral regurgitation and stenosis Patient did well for a 6-7 years, starts developing dyspnea and LE edema Diagnosed with severe pulmonary HTN and told he had no options Becomes despondent and stops following up with his physicians 1-year later presents to the hospital with NYHA class 4 symptoms, ascites, and severe LE edema

46 Mixed Mitral Regurgitation/Stenosis Mean gradient 11 mmhg Mod-sev regurgitation PA pressure mmhg

47 Mixed Mitral Regurgitation/Stenosis

48 Severe Mitral Regurgitation/Stenosis

49 Risk of LVOT Obstruction Depth of implant Flaring of device Mitral-LVOT angle Septal hypertrophy Anterior mitral leaflet

50 Parallel vs Conical deployment

51 Anterior mitral leaflet and LVOT

52 CT scan Annular Area 621 mm2 28 mm Annular Perimeter 92 mm 29 mm Aortic-Mitral angle 113 degrees Derived Diameter

53 Transcatheter Native Mitral Valve Replacement (TMVR)-Sapien XT 29

54 Transcatheter Native Mitral Valve Replacement (TMVR)-Sapien XT 29

55 Transcatheter Native Mitral Valve Replacement (TMVR)-Sapien XT 29

56 Transcatheter Native Mitral Valve Replacement (TMVR)

57 Mean gradient 3 mmhg Mild-moderate regurgitation

58 Hybrid surgical TMVR 81 yo man with severe mitral regurgitation and NYHA class III symptoms. LVEF 50% PMH Severe mitral regurgitation Atrial fibrillation DVT/PE

59 Mitral regurgitation Thickened mitral leaflets (mean gradient 2 mmhg) Decreased posterior leaflet motion Pulmonary venous systolic flow reversal

60 Mitral regurgitation Thickened mitral leaflets (mean gradient 2 mmhg) Decreased posterior leaflet motion Pulmonary venous systolic flow reversal

61 Mitral regurgitation A prior chest CT was evaluated showing significant mitral annular calcification Annular area 826 mm2 Annular diameter 39.8x24.5 mm Aorto-mitral angle 112 degrees

62 Intraoperative TEE Very large annulus Concern for LVOT obstruction

63 Hybrid Surgical Transcatheter TAVR in Mitral Resection of anterior mitral leaflet Six annular sutures were placed Direct deployment of the Edwards Sapien S3 29 mm valve with 4 extra cc s of contrast was performed from the exposed left atrium 80:20 deployment to center the sealing skirt at the annulus level The 6 sutures were then attached to the bottom skirt of the Sapien S3 to secure the valve

64 LVOT obstruction from anterior mitral leaflet Bapat V. Catheter Cardiovasc Interv Oct;86(4):747-60

65 Post-TMV TEE

66 Hybrid surgical-transcatheter TAVR valve for mitral regurgitation Open, direct transcatheter mitral placement using a Sapien S3 valve 80:20 deployment using over-expanded valve Surgical sutures to secure valve and cinch annulus Anterior mitral leaflet resection to avoid LVOT obstruction

67 Mitral valve repair

68 EVEREST 5-Year Results Randomized MitraClip v. Surgery MitraClip184 patients Surgery 95 patients 30d Outcome MitraClip Surgery Blood Transfusion 2 u 13% 45% Repeat Surgery 20% 2.2% MACE (excl. bleeding) 5% 10% Feldman T et al. JACC (25)

69 Clinical improvement-mitraclip Transient drop in LVEF, with recovery/improvement at discharge Improved forward stroke volume Reduction in LVEDD/volumes Reduction in PAP Improved quality of life Improved 6-minute walk times Reduction in BNP Auricchio A Et al. JACC (21) Melisurgo G et al. Am J Cardiol 2014; 113: Grayburn et al. Circulation. 2013;128: Glower DD et al. JACC. 2014, Vol.64(2), p Taramasso et al. EuroIntervention. 2014;10: Frazen O et al. European Journal of Heart Failure (2011) 13,

70 Typical MitraClip Case 69 yo man with LVEF 45% multiple hospitalizations for heart failure, NYHA 3-4

71 Posterior prolapse + annular dilation + redundant leaflet

72 Clip rotation and approach

73 Grasping

74 Second clip laterally

75 Final

76 Mitraclip 76 yo woman EF 20%--biv pacer, moderate severe MR hospitalized x 3 weeks

77 Mitraclip 76 yo woman, EF 20% EF 20%--biv pacer, moderate severe MR hospitalized x 3 weeks

78 Mitraclip 76 yo woman, EF 20% Repeat echo 2 months later: Mild MR, EF 29%

79 COAPT: Study Flow and Follow-up 1576 pts with HF and MR Roll-in cases N=51 at 34 sites Eligible for enrollment N=665 Randomized N=614 at 78 sites Ineligible N=911 Reasons for exclusion Inadequate MR or DMR (n=244) Not treated with GDMT (n=79) All inclusion criteria not met (n=85) Exclusion criteria present (n=34) Echo criteria not met (n=255) Incomplete screening or other (n=419) MitraClip + GDMT N=302 GDMT alone N=312

80 COAPT: Key Inclusion Criteria 1. Ischemic or non-ischemic cardiomyopathy with LVEF 20%-50% and LVESD 70 mm 2. Moderate-to-severe (3+) or severe (4+) secondary MR 3. NYHA functional class II-IVa (ambulatory) despite a stable maximally-tolerated GDMT regimen and CRT (if appropriate) 4. At least one HF hospitalization within 12 months and/or a BNP 300 pg/ml* or a NTproBNP 1500 pg/ml* 5. Not appropriate for mitral valve surgery 6. IC believes secondary MR can be successfully treated by the MitraClip Adjusted by a 4% reduction in the BNP or NT-proBNP cutoff for every increase of 1 kg/m 2 in BMI >20 kg/m 2

81 Baseline Characteristics (ii) HF parameters MitraClip + GDMT (N=302) GDMT alone (N=312) Echo core lab MitraClip + GDMT (N=302) GDMT alone (N=312) Etiology of HF MR severity - Ischemic 60.9% 60.6% - Mod-to-sev (3+) 49.0% 55.3% - Non-ischemic 39.1% 39.4% - Severe (4+) 51.0% 44.7% NYHA class EROA, cm ± ± I 0.3% 0% LVESD, cm 5.3 ± ± II 42.7% 35.4% LVEDD, cm 6.2 ± ± III 51.0% 54.0% LVESV, ml ± ± IV 6.0% 10.6% LVEDV, ml ± ± 72.9 HF hosp w/i 1 year 58.3% 56.1% LVEF, % 31.3 ± ± 9.6 Prior CRT 38.1% 34.9% - 40% 82.2% 82.0% Prior defibrillator 30.1% 32.4% RVSP, mmhg 44.0 ± ± 14.0

82 Cumulative HF Hospitalizations (n) Primary Effectiveness Endpoint All Hospitalizations for HF within 24 months MitraClip + GDMT GDMT alone 283 in 151 pts in 92 pts HR (95% CI] = 0.53 [ ] P<0.001 No. at Risk: MitraClip GDMT Time After Randomization (Months) Median [25%, 75%] FU = 19.1 [11.9, 24.0] mos

83 All-cause Mortality (%) All-cause Mortality 100% 80% 60% 40% MitraClip + GDMT GDMT alone NNT (24 mo) = 5.9 [95% CI 3.9, 11.7] HR [95% CI] = 0.62 [ ] P< % 29.1% 20% No. at Risk: 0% MitraClip + GDMT GDMT alone Time After Randomization (Months)

84 All-cause Mortality or HF Hospitalization (%) Death or HF Hospitalization 100% 80% 60% MitraClip + GDMT GDMT alone HR [95% CI] = 0.57 [ ] P< % 40% 45.7% 20% NNT (24 mo) = 4.5 [95% CI 3.3, 7.2] No. at Risk: MitraClip + GDMT GDMT alone 0% Time After Randomization (Months)

85 24-Month Death or HF Hospitalization Subgroup MitraClip + GDMT GDMT alone HR [95% CI] HR [95% CI] P [Int] All patients Age (median) 74 years (n=317) <74 years (n=297) Sex Female (n=221) Male (n=393) Etiology of cardiomyopathy Ischemic (n=373) Non-ischemic (n=241) Prior CRT Yes (n=224) No (n=390) HF hospitalization within the prior year Yes (n=407) No (n=207) Baseline NYHA class I or II (n=240) III (n=322) IV (n=51) STS replacement score 8% (n=262) <8% (n=352) Surgical risk status* High (n=423) Not high (n=188) Baseline MR grade 3+ (n=320) 4+ (n=293) Baseline LVEF 30% (median; n=301) <30% (median; n=274) >40% (n=103) 40% (n=472) Baseline LVEDV (median) 181 ml (n=288) <181 ml (n=287) 45.7% (129) 52.1% (78) 37.8% (51) 43.2% (39) 47.1% (90) 48.1% (84) 41.1% (45) 50.2% (55) 42.9% (74) 44.7% (86) 47.6% (43) 41.1% (50) 46.6% (67) 68.3% (12) 54.1% (65) 39.2% (64) 49.7% (95) 35.8% (32) 37.5% (51) 53.4% (78) 44.1% (62) 46.4% (56) 49.7% (22) 44.2% (96) 48.9% (43) 41.5% (54) 67.9% (191) 70.2% (100) 65.3% (91) 59.4% (66) 73.0% (125) 70.0% (116) 65.2% (75) 68.4% (69) 67.4% (122) 67.9% (126) 67.8% (65) 66.9% (65) 65.3% (99) 84.4% (26) 71.4% (88) 65.0% (103) 71.5% (140) 58.7% (51) 65.3% (100) 71.4% (91) 61.2% (85) 77.8% (99) 56.2% (27) 71.9% (157) 68.0% (92) 69.5% (92) 0.57 [0.45, 0.71] 0.65 [0.48, 0.88] 0.47 [0.33, 0.66] 0.60 [0.40, 0.89] 0.54 [0.41, 0.71] 0.57 [0.43, 0.76] 0.54 [0.37, 0.78] 0.62 [0.44, 0.89] 0.53 [0.39, 0.71] 0.56 [0.42, 0.73] 0.59 [0.40, 0.86] 0.56 [0.39, 0.81] 0.61 [0.44, 0.83] 0.56 [0.28, 1.12] 0.64 [0.46, 0.88] 0.51 [0.37, 0.70] 0.58 [0.45, 0.75] 0.51 [0.33, 0.80] 0.48 [0.34, 0.67] 0.62 [0.45, 0.83] 0.60 [0.43, 0.84] 0.46 [0.33, 0.64] 0.67 [0.38, 1.17] 0.50 [0.39, 0.65] 0.58 [0.42, 0.80] 0.48 [0.34, 0.67] KM time-to-first event rates *Central eligibility committee assessment Favors MitraClip + GDMT Favors GDMT alone

86 LVEDV (ml) LVEDV change from BL to 12 mo (LSM SE) Change in LVEDV from Baseline to 12 Months GDMT alone MitraClip + GDMT ± Adjusted change* 17.1 ± P< ±76.0 ± ± ± n=174 n=175 n=174 n= Baseline 12 Months -10 *Ancova

87 KCCQ Summary Score KCCQ change from BL to 12 mo (LSM SE) 75 Change in KCCQ from Baseline to 12 Months GDMT alone MitraClip + GDMT 15 Adjusted change* ± ± ±32.0 ± P<0.001 ± ±1.9 n=228 n=236 n=228 n= Baseline 12 Months -6 *Ancova

88 6-Minute Walk Distance (m) 6MWD change from BL to 12 mo (LSM SE) Change in 6MWD from Baseline to 12 Months GDMT alone MitraClip + GDMT ±125.3 ±157.7 ± ± Adjusted change* ± P< n=237 n=229 n=237 n= ±9.0 0 Baseline 12 Months -70 *Ancova

89 24-month rate (%) LVAD or Heart Transplant Within 24 Months GDMT alone (n=312) MitraClip + GDMT (n=302) 7.1 HR [95%CI] = 0.34 [0.13, 0.87] P= HR [95%CI] = 0.35 [0.09, 1.32] P= HR [95%CI] = 0.37 [0.17, 0.81] P= LVAD implant Heart transplant LVAD or HT Stone GW et al. NEJM Sept 23.

90 Death or HF Hospitalization (%) Death or HF Hospitalization (%) COAPT vs. MITRA-FR: 12-Month Death or HF Hosp MITRA-FR COAPT 100% 90% MitraClip + MT MT alone 100% 90% MitraClip + GDMT GDMT alone 80% 70% 60% 50% 40% 30% OR [95% CI]= 1.16 [ ] P= % 51.3% 80% 70% 60% 50% 40% 30% HR [95% CI]= 0.63 [ ] P< % 33.9% 20% 20% 10% 10% 0% 0% No. at Risk: Months No. at Risk: Months Control Group Device Group Control Group Device Group Obadia JF et al. NEJM Aug 27. doi: /NEJMoa Stone GW et al. NEJM Sept 23.

91 Impact of EROA and LVEDV: EROA 30 mm 2 All-cause mortality or HF hospitalization through 12 months 91 LVEDVI >96 ml/m 2 (N=56; 10.2%) LVEDVI 96 ml/m 2 (N=51; 9.3%)

92 Percutaneous Mitral Annuloplasty

93 Percutaneous Annular Solutions Carillon (Cardiac Dimensions) Cardioband (Valtech) AccuCinch (Ancora Heart) Mitralign

94 Carillon (Cardiac Dimensions) AMADEUS Moderate-severe FMR LVESD > 55, EF < 40% 48 patients, 30 successful implants Distal anchor slipped (3) No change in FMR (4) Coronary impingement (1) Coronary impingement and no change in FMR (5) Device fractures (2) Schofer J et al. Circulation. 2009;120:

95 Carillon TITAN 36 patients with implant 17 patients with recaptured/nondeployed devices Tomasz S et al. Eur J Heart Failure )

96 Cardioband (Valtech) 31 patients with mod/sev FMR 100% successful implant No periprocedural deaths Nickeniq G. JACC Cardiovasc Interv Oct 10;9(19):

97 Cardioband (Valtech) 31 patients with moderate to severe FMR and depressed LVEF (34 ± 11%) Mitral regurgitation grade NYHA Class at 7-months Nickeniq G. JACC Cardiovasc Interv Oct 10;9(19):

98 Ventricular solutions? AccuCinch Sub-valvular implant

99 TTE 90 Day Apical 4-chamber (Baseline) Apical 4-chamber (90-day)

100 Day CT - Systolic Baseline ml 90 Day ml Change ml Change % Systolic ml -41% Diastolic ml -20% 1 0 0

101 Accucinch: Strain imaging Pre Post

102 EF% Improvement 30 Days n=9 90 Days n=8 6 Months n= Screening 30 Days Screening 90 Days Screening 6-MO EFS Series-3 Paired Data

103 LVESV (ml) 30 Days n=9 90 Days n=8 6 Months n= % % % Screening 30 Days Screening 90 Days Screening 6-MO

104 QoL Improvements 90 Days KCCQ-Overall Clinical Summary n=11 NYHA n=8 6MWT n= % 75% III % III II Screening 90-Days 25% 0% II Screening I 90 Days 50 0 Screening 90-Days NYHA 1 NYHA 2 NYHA 3 NYHA 4 EFS Series-3 Paired Data

105 MR Grade 30 Days n=9 90 Days n=8 6 Months n=4 100% 100% 100% 90% 90% 90% 80% 80% 80% 70% 70% 70% 60% 60% 60% 50% 50% 50% 40% 40% 40% 30% 30% 30% 20% 20% 20% 10% 10% 10% 0% Screening 30-Day 0% Screening 90-Day 0% Screening 6-MO

106 LV Remodeling Therapy Comparisons Enalapril Carvedilol CRT MV Repair MV Replace MitraClip AccuCinch CONSESUS et al Konstam et al. 1 year Doughty et al Packer et al 1 Year Abraham et al 6 months Acker et al. N Eng J Med year Mitra-FR 1 year AccuCinch 1 Month N=9 AccuCinch 3 Months N=8 AccuCinch 6 Months N=4 Δ EF% Δ ESV (ml) Mortality (% risk reduction) 31% 65% 10% Not Evaluated Not Evaluated No Effect TBD TBD TBD Death or HF Hosp 50% 27% 18% Not Evaluated Not Evaluated No Effect TBD TBD TBD

107 And more to come TRICUSPID VALVE THERAPIES

108 Tricuspid regurgitation Trialign

109 Tricuspid Valve

110 Tricuspid Valve Stenosis

111 Paravalvular leak closure

112 Paravalvular Leak Closure

113 Paravalvular leak closure

114 Conclusions MitraClip COAPT Reduction in Morality and HF hospitalizations?less benefit for large LVEDV and <3+ MR LV or annular modifying therapies may benefit Help us enroll patients! Accucinch Any HFrEF patient with or without MR Cardioband Any moderate-severe MR Carillon Any moderate-severe MR

115 Back-up slides

116 AccuCinch Phase I feasibility study 15 patients with moderate-severe FMR NYHA 2-4 High risk surgical candidate Outcomes Procedural/Technical success Safety at 1, 12 mo Hospitalizations, 6 min walk, QOL, NYHA class

117 Thank you Questions? Creighton W Don University of Washington cwdon@uw.edu (cell) VALV