Prosthesis-Patient Mismatch in High Risk Patients with Severe Aortic Stenosis in a Randomized Trial of a Self-Expanding Prosthesis George L. Zorn, III On Behalf of the CoreValve US Clinical Investigators
Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Proctor/consultant Proctor/consultant Company Medtronic Edwards Under direction from Dr. Zorn, Medtronic performed all statistical analyses and assisted in the graphical display of the data. 2
Background Severe prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) is associated with higher mortality but the association of PPM with transcatheter aortic valve replacement (TAVR) outcomes is unclear PPM has been associated with less LV mass regression at 1 year in SAVR and TAVR patients TAVR may provide an option to reduce PPM and associated clinical events in patients undergoing aortic valve replacement Pibarot P, et al. J Am Coll Cardiol. 2014 3
Study Device and Access Routes 4 Valve Sizes (23, 26, 29, 31 mm) (18-29 mm Annular Range) 18F Delivery System Transfemoral Subclavian Direct Aortic 4
Objective To compare the incidence of PPM between TAVR using a self-expanding prosthesis and SAVR in the CoreValve US High Risk Pivotal Trial To determine the impact of PPM after aortic valve replacement on clinical outcomes 5
Methods Patients with symptomatic severe aortic stenosis at increased risk for surgery were randomized 1:1 to TAVR or SAVR in the CoreValve US High Risk Trial Postoperative PPM was defined by the effective orifice area index (EOAi) Severe PPM was defined as EOAi 0.65 cm 2 /m 2 Moderate PPM was 0.65 < EOAi 0.85 cm 2 /m 2 No PPM was EOAi > 0.85 cm 2 /m 2 This subgroup analysis compares outcomes at 1 year between severe PPM and no severe PPM (EOAi > 0.65 cm 2 /m 2 ) in patients receiving TAVR or SAVR treatment 6
Clinical Demographics Characteristic Severe PPM (N=24) TAVR No severe PPM (N=343) P value Severe PPM (N=75) SAVR No severe PPM (N=259) P value Age 81.5 (8.4) 83.1 (7.0) 0.2756 82.1 (7.0) 83.7 (6.1) 0.0531 Male 11 (45.8) 186 (54.2) 0.4253 34 (45.3) 140 (54.1) 0.1831 BMI 31.9 (7.5) 27.8 (6.0) 0.0016 30.4 (7.9) 28.0 (5.8) 0.0134 NYHA Class III/IV 22 (91.7) 292 (85.1) 0.5517 67 (89.3) 223 (86.1) 0.4660 STS Score (Risk of Mortality, %) 7.3 (2.9) 7.2 (2.9) 0.8368 7.6 (2.9) 7.5 (3.4) 0.7779 Diabetes mellitus 11 (45.8) 121 (35.3) 0.2975 43 (57.3) 111 (42.9) 0.0268 Coronary artery disease 17 (70.8) 262 (76.4) 0.5380 58 (77.3) 195 (75.3) 0.7161 Prior stroke 2 (8.3) 43 (12.5) 0.7524 10 (13.3) 39 (15.1) 0.7012 Prior CABG 6 (25.0) 105 (30.6) 0.5628 26 (34.7) 76 (29.3) 0.3781 Prior PCI 6 (25.0) 118 (34.4) 0.3465 32 (42.7) 97 (37.5) 0.4140 Home oxygen 7 (29.2) 40 (11.7) 0.0134 9 (12.0) 28 (10.8) 0.7726 7
Baseline Echocardiographic Findings Characteristic Severe PPM (N=24) TAVR No severe PPM (N=343) P value Severe PPM (N=75) SAVR No severe PPM (N=259) P value EOAI, cm 2 /m 2 0.32 (0.07) 0.40 (0.12) 0.0005 0.36 0.14) 0.41 (0.12) 0.0109 Aortic Annulus Diameter, cm 2.07 (0.16) 2.23 (0.21) 0.0006 2.14 (0.22) 2.19 (0.21) 0.0676 Doppler Stroke Volume, ml 69.60 (16.92) 76.50 (23.93) 0.2050 69.16 (18.06) 77.45 (20.39) 0.0025 LV Mass, gm 226.45 (60.41) 225.95 (71.69) 0.9781 243.18 (67.42) 224.68 (63.52) 0.0434 LV Mass Index (gm/m 2 ) 119.70 (30.64) 122.29 (35.50) 0.7744 127.29 (33.99) 123.10 (33.43) 0.3790 Ejection Fraction, % 56.04 (12.25) 58.17 (11.25) 0.3737 55.07 (13.04) 58.30 (11.44) 0.0380 Moderate MR (%) 5 (20.8) 31 (9.2) 0.0661 10 (13.5) 26 (10.4) 0.4541 8
Prosthesis-Patient Mismatch Severe PPM occurs significantly more after SAVR than TAVR 9
EOA index: Change from Baseline to 1 Year TAVR SAVR AATS 2015 P-value for change from baseline to 1-Year < 0.001 for all 10
Change in Echocardiographic Findings from Baseline to 1 Year Characteristic Severe PPM TAVR SAVR No severe PPM P value Severe PPM No severe PPM P value AV Peak Velocity (m/s) n=19 n = 270 n = 47 n = 174 Baseline 4.64 (0.63) 4.38 (0.56) 0.0532 4.47 (0.55) 4.34 (0.58) 0.1787 1 Year 2.25 (0.38) 2.01 (0.38) 0.0082 2.68 (0.60) 2.22 (0.55) < 0.0001 Mean Gradient, mmhg n=19 n = 270 n = 47 n = 174 Baseline 52.63 (15.84) 47.74 (13.50) 0.1332 50.13 (16.41) 47.19 (13.69) 0.2119 1 Year 11.18 (3.92) 8.92 (3.41) 0.0060 16.41 (7.74) 11.32 (6.93) < 0.0001 Severe PPM patients had a higher peak velocity and mean gradient than no severe PPM patients in both TAVR and SAVR groups 11
LV Mass Regression % at 1 Year 12
Moderate/Severe AR does not impact LV mass regression P=0.0048 P=0.1269 TAVR LV Mass Index (gm/m 2 13
Clinical Outcomes to 1 Year Characteristic All-Cause Mortality or Major Stroke Severe PPM (N=24) TAVR SAVR Overall No severe PPM (N=343) P value Severe PPM (N=75) No severe PPM (N=259) P value Severe PPM (N=99) No severe PPM (N=602) P value 16.9% 12.3% 0.4927 25.9% 17.6% 0.1099 23.7% 14.6% 0.0188* All-Cause Mortality 16.9% 10.0% 0.2436 21.8% 14.5% 0.1358 20.6% 12.0% 0.0145* Cardiovascular 9.1% 7.4% 0.7696 12.5% 9.2% 0.3882 11.7% 8.2% 0.2326 All Stroke 0.0% 8.3% 0.1623 11.1% 12.6% 0.8184 8.4% 10.1% 0.6756 Major stroke 0.0% 5.3% 0.2663 6.9% 6.1% 0.7367 5.2% 5.7% 0.9284 MI 0.0% 1.8% 0.5237 0.0% 1.6% 0.2849 0.0% 1.7% 0.2068 Reintervention 0.0% 1.5% 0.5706 0.0% 0.0% NA 0.0% 0.9% 0.3863 Life Threatening or Disabling bleeding Major Vascular Complication 26.5% 13.5% 0.1128 35.8% 38.5% 0.6817 33.6% 24.3% 0.0521 4.2% 6.1% 0.6993 2.7% 1.5% 0.5184 3.0% 4.2% 0.6004 Valve Thrombosis 0.0% 0.0% NA 0.0% 0.0% NA 0.0% 0.0% NA Acute Kidney Injury 12.5% 5.5% 0.1633 21.3% 12.4% 0.0476 19.2% 8.5% 0.0008* PPM was defined as severe PPM when the EOAi is 0.65 cm2/m2; No Severe PPM was defined as EOAi >0.65 cm2/m2. *adjusted P=0.0860 for all-cause mortality or major stroke ; adjusted P=0.0666 for all-cause mortality; adjusted P=0.0230 for acute kidney injury 14
All-Cause Mortality, % 1-Year All-Cause Mortality: SAVR Log-rank P=0.14 21.8 13.5 14.5 10.1 No. at Risk Months Post Procedure Severe PPM 75 72 63 56 No severe PPM 259 252 227 212 15
All-Cause Mortality, % 1-Year All-Cause Mortality: TAVR Log-rank P=0.24 12.5 4.4 16.9 10.0 No. at Risk Months Post Procedure Severe PPM 24 23 21 19 No severe PPM 343 342 326 304 16
All-Cause Mortality, % All-Cause Mortality: TAVR+SAVR Log-rank P=0.01 20.6 13.3 6.9 12.0 No. at Risk Months Post Procedure Severe PPM 99 95 84 75 No severe PPM 602 594 553 516 17
Conclusions In this randomized controlled trial of TAVR vs SAVR in the treatment of aortic stenosis in a high risk population: PPM is more common with SAVR than TAVR PPM did not appear to influence LV mass regression within each treatment group but LV mass regression was notably less in the TAVR vs the SAVR group Patients with severe PPM have a higher rate of all-cause mortality and acute kidney injury than patients without severe PPM 18
Limitations Follow-up is only to 12 months and longer-term followup will provide further value There were too few patients with severe PPM in the TAVR treatment group to allow meaningful comparisons of some clinical and echo outcomes. 19
THANK YOU to all the CoreValve Investigators!