2/28/2013. NCDR.13 Workshop 19

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1 NCDR.13 Workshop 19 Patient Selection and Patient Outcomes after Transcatheter Valve Replacement Therapy (TAVR) John D. Carroll, MD, FACC Susan Fitzgerald, RN, MS Presenter Disclosure Information John Carroll, MD, FACC The following relationships exist related to this presentation: Consultation to St. Jude Medical related to Steering Committee Membership of the RESPECT (PFO) Clinical Trial Presenter Disclosure Information Susan Fitzgerald, RN The following relationships exist related to this presentation: No Disclosures 1

2 The STS-ACC Transcatheter Valve Therapy National Registry: A New Partnership and Infrastructure for the Introduction and Surveillance of Medical Devices and Therapies John D. Carroll, MD, Fred H. Edwards, MD, Danica Marinac-Dabic, MD,PhD, Ralph G. Brindis, MD, MPH, Frederick L. Grover, MD, Eric D. Peterson, MD, MPH, Murat Tuzcu, MD David M. Shahian, MD, John S. Rumsfeld, MD, PhD, Cynthia M. Shewan, PhD, Kathleen Hewitt, MSN, RN, David R. Holmes, Jr, MD, Michael J. Mack, MD. Workshop Outline 1. Patient assessment and patient selection for TAVR A. Patient risk B. Frailty C. Health status 2. Key clinical endpoints after TAVR 3. TVT Registry Interim Report Educational Objectives After attending this workshop you should be able to 1. Describeissues revolving around patient assessment and patient selection as outlined in the Expert Consensus Document on Transcatheter Aortic Valve Replacement (TAVR) 2. Discuss key clinical endpoints after TAVR as outlined in the Valve Academic Research Consortium 3. Demonstrate understanding of key metrics in the TVT Registry Interim Report 2

3 History of TAVR In1992 investigators evaluated stentbased bioprostheses delivered to various aortic sites in animal models. History of TAVR: The Sapien Valve 1988: The Idea Henning Rud Andersen, MD He was a fellow in training attending a course in Phoenix when the idea came to him : Early Development Edwards LifeScience, Irvine CA USA Andersen in Denmark Early Prototype ARS #1: When was the first human TAVR performed?

4 ARS #1: First studies: 1992, investigators evaluated stent-based bioprostheses delivered to various aortic sites in animal models. When was the first human TAVR performed? : The first human TAVR was performed 2007: European authorization to perform TAVR procedures (CE Mark approval) 2011: FDA approval of the Edwards Life Science SAPIEN transcatheter heart valve Holmes, D. et al. Expert Consensus Document on TAVR. JACC: 2012;59(13):

5 Expert Consensus Documents (ECD) Informs practitioners concerning evolving areas of clinical practice and/or technologies. The evidence base is not considered sufficiently well developed to be evaluated by the formal ACCF/AHA Practice Guidelines process. The best attempt of the ACCF and document cosponsors to inform and guide clinical practice in areas where rigorous evidence may not yet be available. ECD on TAVR Clinical site selection Operator and team training Patient selection and evaluation Procedural performance and complication management Post procedure care Patient Selection 5

6 ECD on TAVR Patient Selection STS risk score one aspect of patient selection TAVR vsavr Predicts risk of mortality and morbidity (>=10% is high risk) Does not include high risk variables specific to TAVR (e.g. frailty, PH, porcelain aorta, hepatic dysfunction) EuroSCORE II European mortality model Patient Selection Inoperable Inoperability (from the surgeon s judgment) may result from technical considerations that preclude safe performance of AVR. Examples of Inoperable Conditions Prior mediastinal irradiation, Porcelain aorta or severe peri-annular calcification, Severe aortic atheromatous disease, Prior cardiac operations (including the internal mammary artery crossing the midline). Aortic valve bypass with a LV apexto-descending aortic conduit has been used in some patients with severe AS judged to be inoperable via a mediastinal approach 6

7 Patient Selection Prohibitive Risk Associated with prohibitively high morbidity and mortality* and determination of survivability Based on the physician s assessment of the patient s risk for surgery Co-morbidities lead to a limited life expectancy (patients with malignancy, dementia, primary liver disease, chronic obstructive pulmonary disease (COPD) are not appropriate for AVR. Debilitated and deconditioned patients -Frailty and related conditions of debility and deconditioning are known to result in inability to recover. *An estimated >=50% risk of mortality or irreversible morbidity at 30 days (as assessed by 1cardiologist and 2 cardiothoracic surgeons), or other factors such as frailty, technical issues or significant co-morbidities Patient Selection future directions TAVR on lower surgical risk? Example: PARTNER 2: Moderate risk (STS >4) What is Frailty? 7

8 Frailty Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. Fried LP, et al, Frailty in older adults: evidence for a phenotype, J Gerontology: Biological Sciences Mar;56(3):M Frailty Moving from the bedside gestalt to specific, measurable entity A clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. Fried LP, et al, Frailty in older adults: evidence for a phenotype, J Gerontology: Biological Sciences Mar;56(3):M Frailty Assessment the Five Meter Walk 8

9 What gait speed is considered normal? A five meter walk >6 seconds was found to be an independent predictor of mortality Afilalo J, et al,gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing cardiac surgery. JACC. 2010;56: Why do we care about frailty? Treatment risk or treatment benefit Ability to recover from open heart surgery (OHS) Increased vulnerability to adverse events Heath Status and Quality of Life (QOL) Survival marked by reduced physical function or independence may be worse than death 9

10 What is Heath Status? The range of manifestation of disease in a given patient including Symptoms, Functional limitation, and Quality of life What is Quality of Life? The discrepancy between actual and desired function The Range of Health Status Rumsfeld, J. Health Status and Clinical Practice When Will They Meet? Circ 2002; 106:

11 Quality of Life: New York Heart Association (NYHA) class Clinical (not patient) focus Physician rated Easy to use Ratings are variable Quality of Life Kansas City Cardiomyopathy Questionnaire (heart failure related quality of life ) Patient rated outcome Symptoms Physical limitations, Quality of life Social limitations Individual and summary scores KCCQ The baseline assessment predicts Subsequent health status Mortality Morbidity Costs of care above and beyond current clinical measures 11

12 KCCQ Reynolds, M, et all QOL after TAVR. Circ, 2011; 124: Health Status KCCQ Results after TAVR Proportion of patients with a >=20 point increase from baseline score TAVR % (n=179) StandardTherapy % (n=178) 1 month 56.6% 30.3% 12 months 47.5% 13.8% Reynolds, M, et all QOL after TAVR. Circ, 2011; 124: Health Status: Results after TAVR For patients with severe aortic stenosis who were not surgical candidates, TAVR resulted in marked improvements in health status and quality of life compared with standard therapy over 1 year of follow-up. Reynolds et al,quality of Life After TAVR, Circulation 2011, 124:

13 Health Status: Results after TAVR Greatest improvement in health status=physical function Patients who do not experience improvement are more likely to have comorbidities that contribute to continued symptoms and impair quality of life, such as COPD and reduced EF Holmes, D. et al. Expert Consensus Document on TAVR. JACC: 2012;59(13): Health Status: Results after TAVR Reduced health status is a problem for some after TAVR due to Procedure complications (stroke, bleeding, repeat procedures), and poor valve performance Holmes, D. et al. Expert Consensus Document on TAVR. JACC: 2012;59(13): ECD on TAVR -Outcomes 13

14 ECD on TAVR: Early Outcomes The early morbidity of TAVR includes strokes, coronary occlusion, pacemaker implantation, vascular complications, renal failure, cardiac rupture and tamponade, bleeding, aortic dissection, and death. Questions? JACC 2011 Jan; 57(3): and JACC 2012 Oct; 60(15):

15 Valve Academic Research Consortium (VARC) What is it? A consensus report from VARC to propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation investigations in an effort to improve the quality of clinical research and enable meaningful comparisons between clinical trials JACC 2011 Jan; 57(3): 253 Valve Academic Research Consortium (VARC) Who is it? An independent collaboration between academic research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Meetings included representatives from the U.S. Food and Drug Administration, and device manufacturers JACC 2011 Jan; 57(3): 253 VARC: Safety and Efficacy Endpoints Mortality (all cause and cardiovascular) Myocardial infarction (MI) Stroke and TIA Bleeding Acute kidney injury Vascular access site and access-related complications Prosthetic valve performance 15

16 VARC: Myocardial Infarction (MI) Peri-procedural (<=72 hours after index procedure) New ischemic symptoms, AND Elevated cardiac markers Spontaneous (>72 hours after index procedure) Elevated cardiac markers AND ECC changes or imaging evidence, or Sudden cardiac death, or Pathologic findings VARC: Transient Ischemic Attack (TIA) New focal neuro deficit Duration rapid resolution (1-2 hours, always <24 hr) Confirmation(no tissue injury i.e. new abnormality on brain imaging) VARC: Stroke Rapid onset of a focal or global neurodeficit Duration >=24 hours Confirmation(neurology, imaging or lumbar puncture Major vs minor (using Rankin Scale) 16

17 VARC: Bleeding Life threatening or disabling bleeding Major bleeding Minor bleeding Life threatening or disabling bleeding Fatal bleeding OR Bleeding in a critical area or organ, (e.g.intracranial) OR Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery OR Overt source of bleeding with drop in hemoglobin of 5 g/dlor whole blood or packed red blood cells (RBCs) transfusion 4 U Major bleeding Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0 g/dl or requiring transfusion of 2-3 units of whole blood/rbc AND Does not meet criteria of life-threatening or disabling bleeding 17

18 Minor bleeding Any bleeding worthy of clinical mention (e.g., access site hematoma) that does not qualify as life-threatening, disabling or major. VARC: Acute Kidney Injury (AKI) Change in serum creatinine (up to 72 h) compared with baseline Stage 1 to 150% to 200% (1.5 to 2.0 x increase) or increase of >=0.3 mg/dl Stage 2 to 200% to 300% (2.0 to 3.0 x increase) or increase between >0.3 mg/dl and <4.0 mg/dl Stage 3 to 300% (>3 x increase) or >=4.0 mg/dl with an acute increase of at least 0.5 mg/dl or receiving renal replacement therapy VARC: Major Vascular Complications Major Injury of Aorta or Left Ventricle Any aortic dissection, aortic rupture, annulus rupture, left ventricle perforation, or new apical aneurysm/pseudo-aneurysm Distal embolization (non-cerebral) from a vascular source Requiring surgery or resulting in amputation or irreversible end-organ damage 18

19 VARC: Major Vascular Complications Access site or access-related vascular injury leading to death, life-threatening or major bleeding*, visceral ischemia or neurological impairment Dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, compartment syndrome, percutaneous closure device failure VARC: Major Vascular Complications The use of unplanned endovascular or surgical intervention Associated with death, major bleeding, visceral ischemia, or neurological impairment Any new ipsilateral lower extremity ischemia Documented by patient symptoms, physical exam, and/or decreased or absent blood flow on lower extremity angiogram Surgery for access site-related nerve injury Permanent access site-related nerve injury VARC: Prosthetic Valve Dysfunction Aortic stenosis Aortic regurgitation Prosthetic aortic valve thrombosis Endocarditis 19

20 VARC: Prosthetic Valve Associated Complications Conduction disturbances and cardiac arrhythmia Coronary obstruction Composite Endpoints Definition Why Use Composites? VARC Composite Device Success Successful vascular access and deployment of the device, and successful retrieval of the delivery system Correct position of the device in the proper anatomic location Intended performance of the heart valve Only one valve implanted. 20

21 VARC Composite Safety Endpoint at 30 days All-cause mortality Major stroke Life-threatening bleeding Acute kidney injury stage 3 MI Major vascular complication Repeat procedure for valve-related dysfunction VARC Composite Efficacy Endpoint at 1 Year All cause mortality Failure of current therapy for aortic stenosis requiring re-hospitalization Prosthetic heart valve dysfunction Questions? 21

22 STS/ACC TVT Registry Interim Institutional Outcome Reports TVT Registry Reports Phase 1 Institutional Reports Site specific metrics On demand deports Phase 2 Data Quality Program Phase 3 Institutional Outcome Reports & Online Dashboard Executive summary graphics with site specific metrics Registry benchmarks and comparisons Risk adjustment Online dashboard (patient level metric drilldown) Institutional Benchmark Report & Online Dashboard Vendor Vendor TVT DCT Transaction Database Data Quality Engine TVT Registry Data Warehouse Research Projects CMS Reports TVT Exports 22

23 TVT Registry Interim Outcome Report Outline Record counts Procedure volume F/u record count (30 day and 1 year) Process and outcome metrics Discharge 30 days 1 year Sample Interim Report ARS #2: Reports include metrics at discharge, 30 days and 1 year. Which patients are included in the denominator of the 30 day follow-up section of the report? 1. Only patients with a follow-up record 2. Only patients with a follow-up record and/or an adverse event in-hospital 3. All patients 23

24 ARS #2: Which patients are included in the 30 day follow-up section of the report? 1. Only patients with a follow-up record 2. Only patients with a follow-up record and/or an adverse event in-hospital 3. All patients Process Metrics Reporting timeframe Discharge 30 day 1 year Post procedure LOS >6 days x Discharge location x Meds prescribed x x x Process Metrics Meds Prescribed Discharge and 30 days: Aspirin for all patients Patients with no history of atrial fib P2Y12 Patients with a history of atrial fib Warfarin, dabigatran or a P2Y12 One year: Aspirin for all patients 24

25 Outcome Metrics Reporting timeframe Discharge 30 day 1 year Myocardial infarction x x Othercardiac events (pacer insertion, afib, perforation) TIA and stroke (hemorrhagic, ischemic or undetermined) Acute kidney injury(modified RIFLE classification - stage 3) New requirement for dialysis x x x x x x x Post Procedure Afib and Pacemaker: Clinical Trial Experience PARTNER-High risk 1 (U.S.) PARTNER-Inoperable 1 (U.S.) Afib 30 day 8.6% 0.6% Afib 1 year 12.1% 0.6% Pacer 30 day 3.8% 3.4% Pacer 1 year 5.7% 4.5% 1 Expert Consensus Document on TAVR JACC: 2012;59(13): Stroke Clinical Trial Experience Stroke PARTNER-High risk 1 (U.S.) PARTNER-Inoperable 1 (U.S.) International Trials 2 Min, Max, % 30 day 5.5% 7.3% 1-6.8% 1 year 8.3% 11.2% Not reported 1 Expert Consensus Document on TAVR JACC: 2012;59(13): Genereux, et al, Outcomes after TAVR Using VARC Definitions. JACC 2012; 59(25):

26 Clinical Trial: Incidence of Acute Kidney Injury after TAVR Findings at discharge AKI stage 2: 5.1% AKI stage 3: 9.1% Study note: Sample size=100 patients TCT-139 Prognosis and Incidence of AKI According to VARC after TAVR JACC. 2012;60(17_S) Clinical Trail Experience - AKI Implications of AKI stage 2 or 3 Higher rates of In-hospital mortality (any cause) Major bleeding Acute heart failure Infection Total and ICU hospitalization TCT-139 Prognosis and Incidence of AKI According to VARC after TAVR JACC. 2012;60(17_S) Clinical Trail Experience - AKI Implications of AKI stage 3 Worse long term functional outcomes (NYHA class III or IV at six months) TCT-139 Prognosis and Incidence of AKI According to VARC after TAVR JACC. 2012;60(17_S) 26

27 Outcome Metrics Minor bleeding VARC endpoint Reporting timeframe Discharge 30 day 1 year Major bleeding x x Life threatening or disabling x x x Major vascular access site complication requiring Rx x x x x Bleeding At Discharge 10 Bleeding variables in TVT Registry: Hemorrhagic stroke, transapical or transaortic event, bleeding or hematoma at access site, retroperitoneal bleeding, GI, GU or other bleed. Vascular surgery or intervention with a hgb difference of >=3 g/dl. Event qualifier Category(worst) Minor Major Life Threatening Hemoglobin difference (g/dl) <3 * >=3 and <5 >=5 Transfusion (# units) <2 >=2 and <=3 >3 Cause of death=vascular x *Bleeding events with no pre or post hgb qualify as a minor bleed Major bleed Clinical Trial Experience Major Bleed PARTNER-High risk 1 (U.S.) PARTNER-Inoperable 1 (U.S.) 30 day 9.3% 16.8% 1 year 14.7% 17.3% Timeframe not specified International Trials 2 Min, Max, % % 1 Expert Consensus Document on TAVR JACC: 2012;59(13): Genereux, et al, Outcomes after TAVR Using VARC Definitions. JACC 2012; 59(25):

28 Incidence of Bleeding after TAVI Any bleeding event Observed in >25% of the cases and mostly access related Life threatening 13.2% Major 9.2% Minor 4.8% TCT ECD on TAVR: Incidence of Bleeding or Vascular Access Site Complications Transapicalapproach -More major bleeding events (3.9% versus 2.3% for transfemoral) Transfemoral approach More vascular accessrelated complications (11.3% versus 2.0 for transapical approach TAVR SOURCE (SAPIEN Aortic Biosprosthesis European Outcome) Registry Bleeding why is this important? Patients with LTB have a higher 30-day mortality rate (33.3 vs 3.7%) 1 year mortality rate (82% vs 46%) Patients with bleeding after PCI (CathPCI Registry) bleeding after PCI is associated with increased morbidity, mortality and costs. 28

29 Major Vascular Complications: Clinical Trial Experience Major Vascular Complications PARTNER-High risk 1 (U.S.) PARTNER- Inoperable 1 (U.S.) 30 days 17% 16.8% 1 year 18% 17.3% Timeframe not specified International Trials 2 Min, Max, % % 1 Expert Consensus Document on TAVR JACC: 2012;59(13): Genereux, et al, Outcomes after TAVR Using VARC Definitions. JACC 2012; 59(25): Major Vascular Complications 30 days: associated with higher rate of: Major bleeding Transfusion Renal failure requiring dialysis Mortality 1 year: associated with higher mortality rate Genereux, et al, Vascular Complications After TAVR, JACC, Vol. 60, No. 12, 2012 Major Vascular Complications - Independent Predictors Females (predicts major vc) Renal disease at baseline and major vc (predicts 1 year mortality) Genereux, et al, Vascular Complications After TAVR, JACC, Vol. 60, No. 12,

30 ARS #3: Bleeding A patient had a major bleed prior to discharge and is readmitted with a life threatening bleed two weeks later. What would be included in the outcome report? 1. Major bleed at discharge only 2. Major bleed at 30 day follow-up only 3. Major bleed at discharge and life threatening bleed at follow-up 4. Life threatening bleed at follow-up only ARS #3: Bleeding 1. Major bleed at discharge only 2. Major bleed at 30 day follow-up only 3. Major bleed at discharge and life threatening bleed at follow-up 4. Life threatening bleed at follow-up Outcome Metrics Reporting timeframe Discharge 30 day 1 year Device related events* x Mortality (all cause) x x x Death in lab x * Device related events include migration, embolization (into the aorta or into the left ventricle), device retrieval, thrombosis and other events 30

31 All Cause Mortality Clinical Trial Experience All cause mortality PARTNER-High risk 1 (U.S.) PARTNER-Inoperable 1 (U.S.) International Trials 2 Min, Max, % 30 day 3.4% 5.0% % 1 year 24.2% 30.7% % 1 Expert Consensus Document on TAVR JACC: 2012;59(13): Genereux, et al, Outcomes after TAVR Using VARC Definitions. JACC 2012; 59(25): Valve Performance Metrics Device success Reporting timeframe Discharge 30 day 1 year Aortic stenosis x x x Aortic insufficiency (AI) - any x x x AI - perivalvular x x x AI - central x x x Aortic valve re-intervention (surgery or intervention) x x x x Source Registry: Procedural success rate (defined as 1 valve implanted, AR <2+, and patient left procedure room alive) 93% for transfemoral TAVR and 92% for transapical TAVR Interim Report VARC Composites Combined 30 day safety endpoint Combined 1 year efficacy endpoint 31

32 ARS #4: Composites Composites are combined safety and/or efficacy endpoint. They include events such as mortality, stroke and kidney injury. Are they reported as a: 1. Proportion of patients who are event free 2. Proportion of patients with at least one event defined within the composite endpoints ARS #4: Composites are reported as 1. Proportion of patients who are event free 2. Proportion of patients with at least one event defined within the composite endpoints TVT Registry Reports KCCQ at 30 days and 1 year Count of records analyzed (pre and in f/u period) with No or negative change Increase by >=2 points Increase by >=6 points 32

33 Outcomes Report and Quality Improvement Next steps Review consensus document Literature review in the outcomes report companion guide Consider options such as Use of contrast Medications Access site Training Questions? 33