Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
2/28/2013
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
2/28/2013
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.
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
Workshop Outline
1. Describe issues 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
Educational ObjectivesAfter attending this workshop you should be able to…
2/28/2013
3
History of TAVR
• In1992 investigators evaluated stent-
based bioprostheses delivered to various
aortic sites in animal models.
History of TAVR: The Sapien Valve
1988: The IdeaHenning Rud Andersen, MD
He was a fellow in training attending a course in Phoenix when the idea came to him
1988-2002: Early Development
Edwards LifeScience, Irvine CA USA
Early
Prototype
Andersen in Denmark
ARS #1:
When was the first human TAVR performed?
1. 1999
2. 2002
3. 2005
4. 2007
2/28/2013
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?
1. 1999
2. 2002
3. 2005
4. 2008
• 2002: 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):1200-1254
2/28/2013
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
2/28/2013
6
ECD on TAVR – Patient Selection
• STS risk score – one aspect of patient selection
– TAVR vs AVR
– 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
2/28/2013
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 1 cardiologist 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?
2/28/2013
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.
2001 Mar;56(3):M146-56
FrailtyMoving 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. 2001 Mar;56(3):M146-56
Frailty Assessment – the Five Meter Walk
2/28/2013
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;56:1668 –76
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
2/28/2013
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: 5-7
2/28/2013
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
2/28/2013
12
KCCQ
Reynolds, M, et all QOL after TAVR. Circ, 2011; 124: 1964-1972
Health Status
KCCQ – Results after TAVR
Proportion of patients with a
>=20 point increase from baseline score
TAVR %
(n=179)
Standard Therapy %
(n=178)
1 month 56.6% 30.3%
12 months 47.5% 13.8%
Reynolds, M, et all QOL after TAVR. Circ, 2011; 124: 1964-1972
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, 124:1964-1972
2/28/2013
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):1200-1254
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):1200-1254
ECD on TAVR - Outcomes
2/28/2013
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): 253-69
and
JACC 2012 Oct; 60(15):1438-54
2/28/2013
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
2/28/2013
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 neuro deficit
– Duration >=24 hours
– Confirmation (neurology, imaging or lumbar
puncture
– Major vs minor (using Rankin Scale)
2/28/2013
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/dl or 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
2/28/2013
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
2/28/2013
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
2/28/2013
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.
2/28/2013
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?
2/28/2013
22
STS/ACC TVT Registry™
Interim Institutional Outcome Reports
TVT Registry Reports
Phase 1
Institutional
Reports
• Site specific
metrics
• On demand
deports
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)
Data Quality
Program
Phase 2
Data
Quality
Engine
Vendor
TVT
Exports
TVT DCT
Transaction
Database
Research
Projects
CMS
Vendor
Reports
TVT Registry
Data
Warehouse
Institutional Benchmark Report & Online Dashboard
2/28/2013
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
2/28/2013
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
2/28/2013
25
Outcome MetricsReporting timeframe
Discharge 30 day 1 year
Myocardial infarction x x
Other cardiac events (pacer
insertion, afib, perforation)
x
TIA and stroke (hemorrhagic,
ischemic or undetermined)
x x
Acute kidney injury (modified
RIFLE classification - stage 3)
x x
New requirement for dialysis x x
Post Procedure Afib and Pacemaker:
Clinical Trial Experience
PARTNER-High risk1
(U.S.)
PARTNER-Inoperable1
(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%
1Expert Consensus Document on TAVR
JACC: 2012;59(13):1200-1254
Stroke – Clinical Trial Experience
Stroke PARTNER-High risk1
(U.S.)
PARTNER-Inoperable1
(U.S.)
International
Trials2
Min, Max, %
30 day 5.5% 7.3% 1-6.8%
1 year 8.3% 11.2% Not reported
1Expert Consensus Document on TAVR
JACC: 2012;59(13):1200-1254
2Genereux, et al, Outcomes after TAVR Using VARC
Definitions. JACC 2012; 59(25): 2317-26
2/28/2013
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)
2/28/2013
27
Outcome Metrics
VARC endpoint Reporting timeframe
Discharge 30 day 1 year
Minor bleeding x
Major bleeding x x
Life threatening or disabling x x x
Major vascular access site
complication requiring Rx
x x x
Bleeding At Discharge
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
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.
Major bleed – Clinical Trial Experience
Major Bleed
PARTNER-High risk1
(U.S.)
PARTNER-Inoperable1
(U.S.)
International
Trials2
Min, Max, %
30 day 9.3% 16.8%
1 year 14.7% 17.3%
Timeframe not
specified
2.9- 47.0%
1Expert Consensus Document on TAVR
JACC: 2012;59(13):1200-1254
2Genereux, et al, Outcomes after TAVR Using VARC
Definitions. JACC 2012; 59(25): 2317-26
2/28/2013
28
Incidence of Bleeding after TAVI
Any bleeding event
Observed in >25% of the cases and mostly access related
Major
9.2%
TCT 868 - www.jacc.tctabstracts2012.com
Life threatening
13.2%
Minor
4.8%
ECD on TAVR: Incidence of Bleeding or
Vascular Access Site Complications
– Transapical approach - More major bleeding
events (3.9% versus 2.3% for transfemoral)
– Transfemoral approach – More vascular access-
related 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.
2/28/2013
29
Major Vascular Complications:
Clinical Trial ExperienceMajor Vascular
Complications
PARTNER-High
risk1
(U.S.)
PARTNER-
Inoperable1
(U.S.)
International
Trials2
Min, Max, %
30 days 17% 16.8%
1 year 18% 17.3%
Timeframe not
specified
5.0-23.3%
1Expert Consensus Document on TAVR
JACC: 2012;59(13):1200-1254
2Genereux, et al, Outcomes after TAVR Using VARC
Definitions. JACC 2012; 59(25): 2317-26
Major Vascular Complications
Genereux, et al, Vascular Complications After TAVR,
JACC, Vol. 60, No. 12, 2012
• 30 days: associated with higher rate of:
– Major bleeding
– Transfusion
– Renal failure requiring dialysis
– Mortality
• 1 year: associated with higher mortality rate
Major Vascular Complications -
Independent Predictors
Genereux, et al, Vascular Complications After TAVR,
JACC, Vol. 60, No. 12, 2012
• Females (predicts major vc)
• Renal disease at baseline and major vc
(predicts 1 year mortality)
2/28/2013
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
2/28/2013
31
All Cause Mortality – Clinical Trial
Experience
All cause
mortality
PARTNER-High risk1
(U.S.)
PARTNER-Inoperable1
(U.S.)
International
Trials2
Min, Max, %
30 day 3.4% 5.0% 1 - 14.3%
1 year 24.2% 30.7% 15.3- 30.7%
1Expert Consensus Document on TAVR
JACC: 2012;59(13):1200-1254
2Genereux, et al, Outcomes after TAVR Using VARC
Definitions. JACC 2012; 59(25): 2317-26
Valve Performance Metrics
Reporting timeframe
Discharge 30 day 1 year
Device success x
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
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
2/28/2013
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
2/28/2013
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?