Mitral regurgitation severity predicts one year therapeutic benefit

Mitral regurgitation severity predicts one year therapeutic benefit of Tendyne transcatheter mitral valve implantation Vinay Badhwar, Paul Sorajja, Alison Duncan, Vinod Thourani, Ulrich Schaefer, Paul Grayburn, Nicolas Dumonteil, Vasilis Babaliaros, Andrea Garatti, Michael Chuang, Jonathon Leipsic, Philipp Blanke, David Muller

Disclosure Speaker's name : Vinay Badhwar ☑ I have the following potential conflicts of interest to declare: Co-Chair, Tendyne Global Program Executive Committee Uncompensated: Abbott

Background • The longitudinal outcomes of transcatheter therapies for secondary mitral regurgitation (MR) have been variable.

Tendyne TMVI UNIQUE VALVE-TETHER-PAD DESIGN • Repositionable • Fully retrievable • No need for CPB or rapid ventricular pacing APICAL PAD • Placed over ventricular apex TETHER DESIGN • Augments securement VALVE • Tri-leaflet, bioprosthetic valve • Outer frame contoured annulus • Multiple valve sizes and profiles to address range of pathoanatomy

Tendyne TMVI Courtesy of David Muller

Tendyne First 100 Patients J Am Coll Cardiol 2019; 73: 1250– 60

Aims • Examine patients receiving the Tendyne™ Mitral Valve System to identify pre-procedural clinical and echocardiographic predictors of 1 -year benefit following TMVI

Methods • 41 clinical and echocardiographic variables were assessed for association with freedom from death or heart failure hospitalization (HFH) at 1 year • Univariable analysis identified 11 significant variables for inclusion in multivariable model • Multivariable regression performed using 51 patients with complete echocardiographic data

Results Baseline Characteristics Age 75. 6± 7. 5 Gender, Male 76. 5% BSA, m 2 1. 9± 0. 3 Secondary MR 92. 2% NYHA class III/IV 60. 8% Atrial Fibrillation 49. 0% Prior CABG Renal insufficiency (e. GFR<60 ml/min/1. 73 m 2) EROA ≥ 0. 3 cm 2 or Reg Vol ≥ 45 ml 52. 9% History of hypertension 84. 3% STS-PROM, MV replacement 6 MWD, m 8. 5± 6. 1% 244. 7± 133. 2 KCCQ 51. 0± 24. 5 EROA, cm 2 0. 24± 0. 08 Reg Vol, ml 38. 6± 11. 7 LVEDD, cm 6. 0± 0. 7 LVEDV, ml 168. 2± 52. 9 History of CAD 76. 5% LVEDVi, ml/m 2 87. 6± 26. 4 Prior PCI 54. 9% LVEF (%) 45. 8± 10. 3 Valve, LP 15. 7% 70. 6% 31. 4%

Results Baseline Characteristics Age 75. 6± 7. 5 Gender, Male 76. 5% BSA, m 2 1. 9± 0. 3 Secondary MR 92. 2% NYHA class III/IV 60. 8% Atrial Fibrillation 49. 0% Prior CABG Renal insufficiency (e. GFR<60 ml/min/1. 73 m 2) EROA ≥ 0. 3 cm 2 or Reg Vol ≥ 45 ml 52. 9% History of hypertension 84. 3% STS-PROM, MV replacement 6 MWD, m (N) 8. 5± 6. 1% 244. 7± 133. 2 KCCQ 51. 0± 24. 5 EROA, cm 2, (N) 0. 24± 0. 08 Reg Vol, ml, (N) 38. 6± 11. 7 LVEDD, cm 6. 0± 0. 7 70. 6% 31. 4% LVEDV, ml, (N) 168. 2± 52. 9 History of CAD 76. 5% LVEDVi, ml/m 2, (N) 87. 6± 26. 4 Prior PCI 54. 9% LVEF (%) 45. 8± 10. 3 Valve, LP 15. 7%

Results Univariable Predictors Predictor BSA, m 2 Death/HFH 1 yr 1. 9± 0. 3 Odds Ratio (95% CI) 0. 16 (0. 027 - 0. 939) p value 0. 042 15. 4% 0. 20 (0. 052 - 0. 740) 0. 016 5. 9± 0. 7 76. 9% 77. 2± 8. 8 0. 35 (0. 154 - 0. 775) 0. 56 (0. 225 - 1. 366) 1. 09 (1. 028 - 1. 157) 0. 010 0. 200 0. 004 Elevated NT-pro. BNP ≥ 1600 pg/ml 60. 9% 2. 17 (0. 912 - 5. 150) 0. 080 History of coronary artery disease 84. 6% 2. 60 (0. 983 - 6. 880) 0. 054 Valve profile, LP 19. 2% 2. 83 (0. 978 - 8. 177) 0. 055 Renal insufficiency e. GFR<60 ml/min/1. 73 m 2 84. 6% 2. 85 (1. 205 - 6. 756) 0. 017 Prior PCI 65. 4% 3. 31 (1. 415 - 7. 740) 0. 006 History of hypertension 96. 2% 4. 06 (1. 335 - 12. 376) 0. 014 Severe MR - EROA ≥ 0. 3 cm 2/Rvol ≥ 45 ml LVEDD, cm Gender, Male Age

Results Univariable Predictors Predictor BSA, m 2 Death/HFH 1 yr 1. 9± 0. 3 Odds Ratio (95% CI) 0. 16 (0. 027 - 0. 939) p value 0. 042 Severe MR - EROA ≥ 0. 3 cm 2/Rvol ≥ 45 ml 15. 4% 0. 20 (0. 052 - 0. 740) 0. 016 LVEDD, cm 5. 9± 0. 7 0. 35 (0. 154 - 0. 775) 0. 010 Gender, Male Age 76. 9% 77. 2± 8. 8 0. 56 (0. 225 - 1. 366) 1. 09 (1. 028 - 1. 157) 0. 200 0. 004 Elevated NT-pro. BNP ≥ 1600 pg/ml 60. 9% 2. 17 (0. 912 - 5. 150) 0. 080 History of coronary artery disease 84. 6% 2. 60 (0. 983 - 6. 880) 0. 054 Valve profile, LP 19. 2% 2. 83 (0. 978 - 8. 177) 0. 055 Renal insufficiency e. GFR<60 ml/min/1. 73 m 2 84. 6% 2. 85 (1. 205 - 6. 756) 0. 017 Prior PCI 65. 4% 3. 31 (1. 415 - 7. 740) 0. 006 History of hypertension 96. 2% 4. 06 (1. 335 - 12. 376) 0. 014

Results Univariable Predictors Predictor BSA, m 2 Death/HFH 1 yr 1. 9± 0. 3 Odds Ratio (95% CI) 0. 16 (0. 027 - 0. 939) p value 0. 042 15. 4% 0. 20 (0. 052 - 0. 740) 0. 016 5. 9± 0. 7 76. 9% 77. 2± 8. 8 0. 35 (0. 154 - 0. 775) 0. 56 (0. 225 - 1. 366) 1. 09 (1. 028 - 1. 157) 0. 010 0. 200 0. 004 Elevated NT-pro. BNP ≥ 1600 pg/ml 60. 9% 2. 17 (0. 912 - 5. 150) 0. 080 History of coronary artery disease 84. 6% 2. 60 (0. 983 - 6. 880) 0. 054 Valve profile, LP 19. 2% 2. 83 (0. 978 - 8. 177) 0. 055 Renal insufficiency e. GFR<60 ml/min/1. 73 m 2 84. 6% 2. 85 (1. 205 - 6. 756) 0. 017 Prior PCI 65. 4% 3. 31 (1. 415 - 7. 740) 0. 006 History of hypertension 96. 2% 4. 06 (1. 335 - 12. 376) 0. 014 Severe MR - EROA ≥ 0. 3 cm 2/Rvol ≥ 45 ml LVEDD, cm Gender, Male Age

Results Multivariable Predictors Predictor Odds Ratio (95% CI) EROA ≥ 0. 3 cm 2 or Reg Vol ≥ 45 ml 0. 16 (0. 028 – 0. 852) Prior PCI 6. 44 (1. 219 – 34. 08) Renal insufficiency 8. 15(1. 351 – 49. 18) History of hypertension 20. 7 (0. 795 – 541. 1) ↑ 1 -year death/HFH PCI, Renal insufficiency, Hypertension ↓ 1 -year death/HFH More severe MR

Results Less Severe vs. More Severe MR Less Severe MR EROA<0. 3 cm 2/Reg Age, years Vol<45 ml More Severe MR EROA≥ 0. 3 cm 2/Reg Vol≥ 45 ml p value 75. 5± 7. 6 75. 7± 7. 5 0. 950 74. 3% 81. 3% 0. 730 STS Risk of Mortality 9. 5± 6. 6 6. 3± 4. 2 0. 083 NYHA class III/IV % 65. 7% 50. 0% 0. 360 Prior PCI % 54. 3% 56. 3% >0. 999 Renal insufficiency, % 74. 3% 62. 5% 0. 510 Hypertension % 88. 6% 75. 0% 0. 240 79. 7± 25. 5 104. 0± 20. 6 0. 002 5. 9± 0. 6 6. 4± 0. 6 0. 012 62. 9% 25. 0% 0. 017 Gender, Male % (n) LVEDVi ml/m 2 LVEDD cm Death/HFH at 1 yr %

Essential Results • Increased 1 year Death/HFH associated with renal failure, prior PCI, hypertension • More severe MR predictive of Tendyne TMVI 1 year freedom from Death/HFH

Conclusions • Tendyne TMVI 1 year outcome benefit with severe MR • HF symptoms driven by the severity of MR rather than other comorbidities • May inform therapy selection for secondary MR and left ventricular dilatation

Tendyne: Exclusively for clinical investigations. Tendyne is currently in development at Abbott and being evaluated in clinical trials and is intended for use by or under the direction of a physician. Not available for sale.