TVT Registry WS 19 ANSWERS REMOVED.ppt

2/28/2013

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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

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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…

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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

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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

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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

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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

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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?

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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

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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

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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

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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

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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

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• 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


• 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

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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

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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

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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)

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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

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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

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• 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


• 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

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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.

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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?

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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

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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


and/or an adverse event in-hospital

3. All patients

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ARS #2:

Which patients are included in the 30 day

follow-up section of the report?



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

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Outcome MetricsReporting timeframe


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


JACC: 2012;59(13):1200-1254

2Genereux, et al, Outcomes after TAVR Using VARC

Definitions. JACC 2012; 59(25): 2317-26

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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


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)


JACC. 2012;60(17_S)

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Outcome Metrics

VARC endpoint Reporting timeframe


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%


JACC: 2012;59(13):1200-1254



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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.

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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%


JACC: 2012;59(13):1200-1254



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)

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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


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

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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%


JACC: 2012;59(13):1200-1254



Valve Performance Metrics

Reporting timeframe


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

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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

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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?