TAVR SPRING 2017 The evolution of TAVR

Transcription

1 TAVR SPRING 2017 The evolution of TAVR Matthew Johnson, MD Disclosers None Evolution of the Balloon- Expandable Transcatheter Valves Cribier 2002 SAPIEN 2006 SAPIEN XT 2009 SAPIEN * Sheath compatibility for a 23 mm valve Nithin P G 1

2 Introduction Symptomatic Severe Aortic Stenosis AV R 30-40% do not undergo Sx Advanced age LV dysfunction Multiple co-morbidities Pt. preference Physician assessment High risk for surgery Complications Prohibitive risk Inoperability ~3% mortality (STS, EuroSCORE) ~2% Stroke ~11% prolonged ventilation Organ failure Thromboembolic Complications Bleeding Prosthetic valve Dysfunction Indications 2012 A Symptomatic severe calcific Aortic Stenosis [trileaflet] who have aortic and vascular anatomy suitable for TAVR and a predicted survival >12 months, and who have a prohibitive surgical risk as defined by an estimated 50% or greater risk of mortality or irreversible morbidity at 30 days or other factors such as frailty, prior radiation therapy, porcelain aorta, and severe hepatic or pulmonary disease. TAVR is a reasonable alternative to surgical AVR in patients at high surgical risk (PARTNER Trial Criteria: STS >8) Indications Patient selection in clinical trials Logistic EuroSCORE >20% or STS Score > 10. Nithin P G 2

3 Indications Requisites Heart team approach Specific team leader Close communication Preplanning procedure Large cathlabs/ hybrid rooms Fluoroscopic imaging TEE capabilities GA/ CPB Vascular intervention Urgent AVR, CABG, Vascular complications Anesthesia Conscious sedation/ GA CPB facility Hemodynamic monitoring and management Pre-anesthetic work up Work up Cardiothoracic evaluation [access, AVR, risk assessment] Imaging AS severity, morphology, calcification, annular size and shape Aortic root, annulus to coronary ostia (>8mm), Atheroma burden, calcification Other valvular disease, sub aortic obstruction LV function Vascular anatomy from access site to annulus Cerebro vascular imaging Nithin P G 3

4 Work up Role of imaging in pre-procedural and post procedural assessment Transcatheter Aortic Valve Intervention Procedure & Hardware Procedure & Hardware LA + Conscious sedation/ GA, hemodynamic stability [ SBP~120 mm Hg / MAP >75 mm Hg] Vascular access Sites Transfemoral Transapical Left ant. thoracotomy More direct, shorter catheter Septal hypertrophy Ascendra2, Sapien valve Transaortic Upper partial sternotomy Mini-sternotomy 2/3 RICS Aorta 5 cm above valve Less painful, familiar approach Manipulation of ascending aorta Subclavian Percutaneous or Cut-down technique Nithin P G 4

5 Procedure & Hardware Pacing leads Trans venous or epicardial TEE- Mid esophageal Anticoagulation long axis view Large sheaths Heparin [ACT>300] Intra-procedural TEE Guidewire placement Valve placement Stable position No coronary obstruction No interference with mitral valve function No conduction system impingement No overhanging native aortic leaflets Avoidance of aortic root complications (rupture & dissection) Post deployment assessment [MR, AR] Sapien XT device Procedure & Hardware CoreValve device Self expandable Nitinol frame Porcine Pericardial Tissue European Heart Journal (2011) 32, Superior hemodynamics Lower risk for PPM Cardiol Clin 29 (2011) Procedure & Hardware Pressure tracings before and after TAVR European Heart Journal (2011) 32, Nithin P G 5

6 Procedure & Hardware European Heart Journal (2011) 32, Post-Operative Care & Monitoring Immediate or early extubation, early mobilization Adequate analgesia, control postoperative hypertension, monitor for any bleed Monitor vital parameters including fluid balance, renal status, and AV conduction system. Pre-discharge TTE, DAPT,Coumadin vs NOAC Complications & Management Nithin P G 6

7 Complications & Management Left main stem compromise with semi-occlusive displacement of calcified nodule from aortic valve. Treated with CPB device explantation AVR Also PCI/CABG Cardiol Clin 29 (2011) Complications & Management Incidence of CHB requiring permanent pacemaker implantation has been higher with the CoreValve (19.2% to 42.5%) than with the Sapien valve (1.8% to 8.5%) [larger profile and extension low into the LVOT Occurrence of CHB/LBBB BAV 46% Balloon/prosthesis positioning &wire-crossing of the aortic valve 25% Prosthesis expansion 29%. Pre-existing RBBB risk factor for CHB Complications & Management Aortic Regurgitation Typically paravalvular mild or mild-moderate severity Most of AR disappears or reduces at 1 yr follow-up [13% absent, 80% mild AR] Cardiol Clin 29 (2011) J. Am. Coll. Cardiol. 2012; 59; Nithin P G 7

8 Complications & Management Paravalvular AR Central valvular AR Post-deployment balloon dilation, rapid RV pacing for stabilization, valve in valve implantation Usually self-limited, Gentle probing of leaflets with a soft wire or catheter Delivery of a 2 nd TAVR device, valve in valve Complications & Management Rapid Pacing for stabilization Reduction of diastole Valve in Valve Implantation Cardiol Clin 29 (2011) Complications & Management Causes of hypotension after TAVI Vascular complications iliac rupture Ventricular rupture Acute valve dysfunction Coronary artery obstruction Multiple rapid pacing episodes in pts with poor LV function Suicidal LV in severe LVH [After removing AV obstruction LV decompresses to such an extent that the subvalvular hypertrophy obstructs outflow] treated with fluids & avoiding diuretics Cardiol Clin 29 (2011) Nithin P G 8

9 Complications & Management Significant annular rupture Ventricular perforation Pericardial drainage, auto-transfusion Conversion to open surgical closure Device malposition Device embolization Overlapping valve in valve Urgent endovascular/ surgical management Major ischemic stroke Minor ischemic stroke Hemorrhagic stroke Catheter-based, mechanical embolic retrieval Aspirin, anticoagulants Anticoagulation reversal, coagulopathy correction Complications & Management Atrial fibrillation Rate control/ rhythm control via pharmacological or electrical cardioversion Shock, low cardiac output Major bleeding Vascular complications Careful systemic pressure management, inotropic support, IABP, or CPB Hemodynamic support, blood transfusion Urgent endovascular repair/surgery Transcatheter Aortic Valve Intervention Review of evidence Nithin P G 9

10 Registry data Age> 80 years Review of Evidence EuroSCORE [> 23 Sapien, >16 CoreValve ] Route of implantation no difference in procedural success rate b/w TF & TA accesses Major bleeding more in TA vs. more vascular complications in TF Review of Evidence PARTNER Trial Design Cohort A 84 yrs N=699 Cohort B 83 yrs N=358 Background Based on randomized trials with first generation devices, transcatheter aortic valve replacement (TAVR) has been incorporated into the treatment strategy for high-risk and inoperable patients with severe AS. Procedural complications remain a concern with TAVR, including stroke, vascular complications, paravalvular leak (PVL) and conduction disturbances. Addressing these limitations will support TAVR use in lower risk populations. Nithin P G 10

11 Evolution of the Balloon- Expandable Transcatheter Valves Cribier 2002 SAPIEN 2006 SAPIEN XT 2009 SAPIEN * Sheath compatibility for a 23 mm valve SAPIEN 3 Transcatheter Heart Valve Distinguishing Features Enhanced frame geometry for ultra-low delivery profile Low frame height Bovine pericardial tissue Outer skirt to reduce PVL SAPIEN 3 Commander Delivery System Distinguishing Features Improved coaxial alignment Accurate positioning Distal flex Fine control of valve positioning SAPIEN 3 Valve Size 20 mm 23 mm 26 mm 29 mm Expandable Sheath 14F 14F 14F 16F Minimum Access Vessel Diameter 5.5 mm 5.5 mm 5.5 mm 6.0 mm Nithin P G 11

12 The PARTNER II Program Purpose To evaluate the safety and efficacy of the SAPIEN 3 transcatheter heart valve system at 30 days in inoperable, high-risk, and intermediate-risk patients. The PARTNER II S3 Trial Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT by Heart Valve Team n = 1076 Patients Intermediate Risk Operable (PII S3i) SAPIEN 3 2 Single Arm Non-Randomized Historical-Controlled Studies High Risk Operable / Inoperable (PII S3HR) n = 583 Patients ASSESSMENT: Optimal Valve Delivery Access PII A SAVR PI A SAPIEN ASSESSMENT: Optimal Valve Delivery Access Transfemoral (TF) Transapical / Transaortic (TA/TAo) Transfemoral (TF) Transapical / Transaortic (TA/TAo) TF TAVR SAPIEN 3 TAA TAVR SAPIEN 3 TF TAVR SAPIEN 3 TAA TAVR SAPIEN 3 Key Inclusion Criteria Risk determined by STS score and heart team: High Risk / Inoperable (S3HR): STS score > 8 or heart team determination Intermediate Risk (S3i): STS score between 4 and 8 or heart team determination Severe aortic stenosis determined by echocardiography: Valve area < 0.8 cm 2 or Valve area index < 0.5 cm 2 /m 2 and mean gradient > 40mmHg or peak velocity > 4 m/s Nithin P G 12

13 Key Exclusion Criteria MI within one month Bicuspid aortic valve Severe aortic regurgitation Prior prosthetic valve in any position Untreated significant CAD (S3HR only) LVEF < 20% Stroke or TIA within 6 months Upper GI bleed within 3 months Creatinine > 3.0 or dialysis Estimated life expectancy < 24 months Study Methodology All patients presented on a screening call for approval prior to implant. 3D imaging of annulus (CT or 3D TEE) recommended for S3HR and required for majority of S3i with core lab analysis prior to implant. All patients evaluated by a neurologist at baseline and at follow-up time points. Primary Analysis: As treated patients S3HR and S3i combined for echocardiographic analyses (valve implant patients). Study Flow: S3HR & S3i 30 Day Patient Status S3HR n = Deaths n = 570 SAPIEN 3 0 Withdrawal 3 LTFU 567 / 570 or 99.5% follow-up visits performed at 30 Days S3i n = Deaths n = 1064 SAPIEN 3 0 Withdrawal 5 LTFU 1059 / 1064 or 99.5% follow-up visits performed at 30 Days Nithin P G 13

14 Baseline Patient Characteristics S3HR Patients Average STS = 8.6% (Median 8.4%) Average Age = 82.6yrs N = 583 Baseline Patient Characteristics S3i Patients Average STS = 5.3% (Median 5.2%) Average Age = 81.9yrs N = 1076 Baseline Patient Characteristics Demographics Characteristic (%) S3HR (n=583) S3i (n=1076) NYHA Class III or IV Previous CABG Previous CVA Peripheral Vascular Disease Diabetes COPD - O 2 Dependent CKD - Creat. 2mg/dL Atrial Fibrillation Permanent Pacemaker Frailty Nithin P G 14

15 Baseline Echocardiography Characteristic S3HR (n=583) S3i (n=1076) AV Area - cm 2 (mean ± SD) 0.67 ± ± 0.17 Annulus Diam. - cm (mean ± SD) 2.2 ± ± 0.2 AV Gradient - mmhg (mean ± SD) 45.5 ± ± 12.7 LV Ejection Fraction (%) 56.4 ± ± 13.3 Mod-Severe MR (%) Procedural Factors S3HR (n=583) S3i (n=1076) Post-Dilatation (%) >1 Valve Implanted (%) Valve Embolization (%) IABP During Procedure (%) Cardiopulmonary Bypass (%) Conscious Sedation (%) Median LOS Days (Min, Max) 5 (1, 33) 4 (1, 64) Mortality and Stroke: S3HR At 30 Days (As Treated Patients) Mortality Stroke % O:E = 0.26 (STS 8.6%) % Nithin P G 15

16 Mortality and Stroke: S3i At 30 Days (As Treated Patients) Mortality Stroke O:E = 0.21 (STS 5.3%) % % Mortality: S3HR & S3i At 30 Days (As Treated Patients) Transfemoral Transapical / Transaortic % All-Cause Mortality at 30 Days SAPIEN Valves (As Treated Patients) PARTNER I and II Trials Overall and TF Patients SAPIEN SXT SAPIEN 3 Nithin P G 16

17 All-Cause Mortality at 30 Days SAPIEN Valves (As Treated Patients) PARTNER I and II Trials TA/TAo Patients Nested Registries SAPIEN SAPIEN XT SAPIEN 3 Strokes At 30 Days (As Treated Patients) Events (%) S3HR Overall (n=583) S3HR TF (n=491) S3HR TA/TAo (n=92) S3i Overall (n=1076) S3i TF (n=951) S3i TA/TAo (n=125) All Disabling* Non-Disabling TIA *CEC adjudicated or Modified Rankin Score 2 at 30 days All Strokes at 30 Days SAPIEN Valves PARTNER I and II Trials Neurologist evaluations (pre- and post) SAPIEN SAPIEN XT SAPIEN 3 Nithin P G 17

18 Other Clinical Events At 30 Days (As Treated Patients) Events (%) S3HR Overall (n=583) S3HR TF (n=491) S3HR TA/TAo (n=92) S3i Overall (n=1076) S3i TF (n=951) S3i TA/TAo (n=125) Major Vascular Comps Bleeding - Life Threatening Annular Rupture Myocardial Infarctions Coronary Obstruction Acute Kidney Injury New Permanent Pacemaker Aortic Valve Re-intervention Endocarditis NYHA Functional Class At 30 Days (As Treated Patients) 13% 6% % 90% 73% IV III II I Baseline 30 Days Echo Findings: S3HR & S3i Aortic Valve Area (Valve Implant Patients) No. of Echos Overall Nithin P G 18

19 Valve Area (cm²) Echo Findings: S3HR & S3i Aortic Valve Area (Valve Implant Patients) Overall 29 mm 26 mm 23 mm 20 mm No. of Echos Baseline 30 Days Overall Echo Findings: S3HR & S3i Mean Gradients (Valve Implant Patients) No. of Echos Overall Gradient (mmhg) Echo Findings: S3HR & S3i Mean Gradients (Valve Implant Patients) Overall mm mm mm mm No. of Echos Baseline 30 Days Overall Nithin P G 19

20 Paravalvular Leak: S3HR & S3i (Valve Implant Patients) 0.1% No. of Echos 1504 Moderate/Severe PVL at 30 Days SAPIEN Valves PARTNER I and II Trials SAPIEN SAPIEN XT SAPIEN 3 Nithin P G 20

21 Conclusions (1) In high-risk and inoperable patients (S3HR), the SAPIEN 3 TAVR system demonstrated low mortality and stroke and excellent clinical outcomes at 30 days: Mortality: 2.2% (TF 1.6%, TA/TAo 5.4%) Disabling Stroke: 0.9% In intermediate-risk patients (S3i), SAPIEN 3 was associated with strikingly low mortality and strokes at 30 days: Mortality: 1.1% (TF 1.1%, TA/TAo 1.6%) Disabling Stroke: 1.0% Nithin P G 21

22 Conclusions (2) Other important clinical findings with SAPIEN 3 (both S3HR & S3i) include: Major vascular complications: ~5% Annular rupture: ~0.2% Coronary obstruction: ~0.3% New pacemakers: ~10% Significant paravalvular regurgitation with SAPIEN 3 (both S3HR & S3i) was rare: Severe: 0.1% Moderate: 3.7% Implications The rapid evolution of balloon-expandable TAVR, both procedural developments and technical enhancements, represented in the SAPIEN 3 clinical and echo results, indicates at least parity with the best surgical outcomes in comparable patients. SAPIEN 3 TAVR should now be considered as an alternative to surgery, even in lower risk patients with aortic stenosis. Thank You Nithin P G 22