Sixth Annual Meeting March 12, 2012 8:00am to 4:00pm Crowne Plaza National Airport Arlington, VA

Sixth Annual MeetingMarch 12, 2012

8:00am to 4:00pm

Crowne Plaza National AirportArlington, VA

Research Symposium

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What are the outstanding issues with VADs? Which of these can be answered by INTERMACS?

Robert Kormos, MD

Sixth Annual Meeting, March 12, 2012

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How can INTERMACS help shape the Future of MCS?

• Where is the field today?

• Recap the role of INTERMACS

• Destination Therapy: Evolving

• Heart Transplantation: Also Dynamic

• Major Challenges to MCSD Therapy

• Upcoming Initiatives to Help Answer the Questions

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Dr. Marvin Slepian, University of ArizonaIN

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Changing the Life Cycle of New Technology

Bowling Alley

Bowling Alley

Paradigm Shift 1

Paradigm Shift 2

Torn

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Value Added

Adjuvant functionsControlsChangeable partsR and L componentsWear indicatorsForgettable

ISHLT 2004IN

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Dr. Marvin Slepian, University of ArizonaIN

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Temporary Devices (include only in conjunction LVAD, BIVAD, TAH with a durable device listed above)HeartMate II LVAS Abiomed AB5000HeartMate IP Abiomed BVS 5000HeartMate VE Levitronix CentrimagHeartMate XVE TandemHeartMicromed DeBakey VAD – ChildNovacor PCNovacor PCqThoratec IVADThoratec PVADAbiocor TAHSyncardia Cardiowest

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Later this afternoon, Dr. Tim Baldwin will show the (miniature) pediatric devices that will be part of the PumpKiN Trial

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• Destination Therapy : Evolving




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INTERMACS Hospital Enrollment

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Pulsatile Flow Intracorporeal LVAD Pump

Continuous Flow Intracorporeal LVAD Pump

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Cont Intra Pump 1 1 464 843 1526 1548

Puls Intra TAH 2 22 22 24 27 15

Puls Intra Pump 82 263 183 55 12 2

Puls Para Pump 18 61 74 71 36 55

Pulsatile Flow Paracorporeal LVAD Pump

Primary Implant Enrollment: n=5407

: June 2006 – December 2011

Pulsatile Flow Intracorporeal TAH

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Continuous Flow Intracorporeal Device n=896, deaths=112

Pulsatile Flow Paracorporeal Device, n=74, deaths=28

p (overall) < 0.0001

Event: Death (censored at transplant or recovery)

% S

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Months after Device Implant

Pulsatile Flow Intracorporeal Device, n=470, deaths=140

INTERMACS: Survival After LVAD Implant

Implants: June 2006 – March 2010

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Evolution from“Transplant Ineligible”

to“Transplant Alternative”

Destination Therapy


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Long-Term Use of a Left Ventricular Assist Device for End-Stage Heart Failure (for the REMATCH Study Group). N Engl J Med 2001; 345:1435-1443; Nov 15, 2001

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Long-Term Destination Therapy With the HeartMate XVE Left Ventricular Assist Device: Improved Outcomes Since the REMATCH Study. Congestive Heart Failure, 11: 133–138.


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Event: Death (censored at transplant or explant recovery)

: June 2006 – June 2011 Primary Continuous Flow LVADs (+/- RVADs): n= 3405*

Overall Survival

Bridge to Transplant Listed, n=1221, deaths=153

By initial Device Strategy

Bridge to Candidacy, n=1391, deaths=247

p < .0001

*An additional 53 pts had initial device strategy of rescue therapy (n=11), recovery (n=21) and other (n=21). These patients are not included in the figure.

Destination Therapy, n=740, deaths=132

Figure 10 12/14/2011INTERMACS A

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BTT

Other*

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BTC 36 132 302 433 598 600

BTT 45 148 367 491 463 370

DT 16 47 47 47 511 620

DT

Primary Implant Enrollment: n=5407


BTC

* Other includes bridge to recovery, rescue therapy and miscellaneous. INTERMACS A

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Cont Intra Pump 1 0 6 26 508 619

Puls Intra Pump 15 47 41 20 3 0

Primary Implant Enrollment, Destination Therapy: n=1286


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Survival to 1 Year After Transplant for Adult Heart Transplants Performed Between January 1982 and June 2009, Stratified by Era of Transplant.

The Registry of the International Society for Heart and Lung Transplantation-Twenty-eighth Adult Heart Transplant Report-2011. JHLT. 2011 Oct;30(10):1078-1094.IN

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CTRD: 1990 - 2001

Years After Transplant

Status II Patient

Predicted Survival of a Status II Patient

Smoker

No comorbid conditions

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CTRD: 1990 - 2001


Status II Patient


Smoker

Smoker, Diabetic


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CTRD: 1990 - 2001


Status II Patient


Smoker

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Smoker, Diabetic, Hx ofPulmonary Vascular Disease


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Major Challenges

1. Accurate contemporary risk-adjusted depictions of survival after cardiac transplantation

2. Risk-adjusted contemporary survival after mechanical circulatory support

3. Effective analyses that unveil the shortcomings of MCS therapy


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Major Challenges

4. Find “common ground” between Cardiac Transplantation and MCS analyses that accommodate the differing patient populations in Cardiac Transplantation, Destination Therapy – Transplant Ineligible, and Destination Therapy – Transplant Alternative


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Major Challenges

5. Develop analyses that are sensitive to the evolution of individual devices and device categories as we allocate device therapies.


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Specific Adverse Events that challenge the long-term implementation of MCS:

•Early mortality and its causes•Infection of driveline and pump pockets•Right Ventricular Failure•Pump and Outflow Graft Thrombosis•Renal Dysfunction

Plus Quality of Life and Functional Capacity


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Coordinator Training Session, March 11, 2012

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Device Malfunction

Device malfunction denotes a failure of one or more of the components of the MCSD system which either directly causes or could potentially induce a state of inadequate circulatory support (low cardiac output state) or death . The manufacturer must confirm device failure. A failure that was iatrogenic or recipient-induced will be classified as an Iatrogenic/Recipient-Induced Failure.

Device failure should be classified according to which components fails as follows:

1) Pump failure (blood contacting components of pump and any motor or other pump actuating mechanism that is housed with the blood contacting components). In the special situation of pump thrombosis, thrombus is documented to be present within the device or its conduits that result in or could potentially induce circulatory failure.

2) Non-pump failure (e.g., external pneumatic drive unit, electric power supply unit, batteries, controller, interconnect cable, compliance chamber)

The Adverse Event: Device Malfunction Form is to be collected at time of event. FDA has set forth regulations regarding these events. For the purposes of submitting adverse event device malfunction information to the FDA, you must enter any device malfunction event that occurs within 72 hours of the event.

INTERMACS Protocol 3.0 - Mar 5, 2012IN

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Major Infection

A clinical infection accompanied by pain, fever, drainage and/or leukocytosis that is treated by anti-microbial agents (non-prophylactic). A positive culture from the infected site or organ should be present unless strong clinical evidence indicates the need for treatment despite negative cultures. The general categories of infection are listed below:

Localized Non-Device InfectionInfection localized to any organ system or region (e.g. mediastinitis) without evidence of systemic involvement (See sepsis definition), ascertained by standard clinical methods and either associated with evidence of bacterial, viral, fungal or protozoal infection, and/or requiring empirical treatment.

Percutaneous Site and/or Pocket InfectionA positive culture from the skin and/or tissue surrounding the drive line or from the tissue surrounding the external housing of a pump implanted within the body, coupled with the need to treat with antimicrobial therapy when there is clinical evidence of infection such as pain, fever, drainage, or leukocytosis.

Internal Pump Component, Inflow or Outflow Tract InfectionInfection of blood-contacting surfaces of the LVAD documented by positive site culture. (There should be a separate data field for paracorporeal pump that describes infection at the percutaneous cannula site, e.g. Thoratec PVAD).

SepsisEvidence of systemic involvement by infection, manifested by positive blood cultures and/or hypotension.


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Continuous Intracorporeal pump, n=896, infections=265

P < .0001

Event: First Infection

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Pulsatile Intracorporeal pump, n=470, infections=190

Months Continuous Pulsatile/IntraPost Implant (n=896) (n=470) 1 81% 72% 3 74% 59% 6 67% 51% 12 61% 42% 24 58% 37%

% Free of Infection

INTERMACS: June 2006 – September 2009: Infection Study

Adult Primary intracorporeal LVADs: 1366

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Continuous intracorporeal pump, n=896, infections=77

P < .0001

Event: First pump pocket or drive line infection

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Pulsatile intracorporeal pump, n=470, infections=105

Months Continuous Pulsatile/IntraPost Implant (n=896) (n=470) 1 99% 96% 3 96% 87% 6 91% 77% 12 85% 64% 24 80% 62%

% Free of Pump pocket or Drive line Infection

INTERMACS: June 2006 – September 2009: Infection Study

Adult Primary intracorporeal LVADs: 1366

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Months after Implant

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p < .0001

Continuous Flow Pump, n=2006, first DL infections=197

Pulsatile Flow Pump, n=484, first DL infections=81

Months % Freedom 1 99% 6 93% 12 81% 24 74%

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Neurological Dysfunction

Any new, temporary or permanent, focal or global neurological deficit ascertained by a standard neurological examination (administered by a neurologist or other qualified physician and documented with appropriate diagnostic tests and consultation note). The examining physician will distinguish between a transient ischemic attack (TIA), which is fully reversible within 24 hours (and without evidence of infarction), and a stroke, which lasts longer than 24 hours (or less than 24 hours if there is evidence of infarction). The NIH Stroke Scale (for patients > 5 years old) must be re-administered at 30 and 60 days following the event to document the presence and severity of neurological deficits. Each neurological event must be subcategorized as:

1) Transient Ischemic Attack (acute event that resolves completely within 24 hours with no evidence of infarction)

2) Ischemic or Hemorrhagic Cardiovascular Accident/CVA (event that persists beyond 24 hours or less than 24 hours associated with infarction on an imaging study.)


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IMACS 3, n=172, neuro events=12

Event: First Neurological Event

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p = .08

Adult Primary Continuous Intracorporeal LVADs: 896By INTERMACS Patient Profile Levels

INTERMACS: June 2006 – September 2009: Neurological Dysfunction

IMACS 4-7, n=156, neuro events=15

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Adult Primary Pulsatile Intracorporeal LVADs: 470By INTERMACS Patient Profile Levels

INTERMACS: June 2006 – September 2009: Neurological Dysfunction

IMACS 4-7, n=64, neuro events=11

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MAJOR BLEEDINGAN EPISODE OF SUSPECTED INTERNAL OR EXTERNAL BLEEDING THAT RESULTS IN ONE OR MORE OF THE FOLLOWING:

1. Death,2. Re-operation,3. Hospitalization,4. Transfusion of red blood cells

If TRANSFUSION IS SELECTED, then apply the following rules:During first 7 days post implant:

Adults (≥ 50 kg): ≥ 4U packed red blood cells (PRBC) within any 24 hour period during first 7 days post implant.

After 7 days post implant Any transfusion of packed red blood cells (PRBC) after 7 days

following implant with the investigator recording the number of units given.

Note: Hemorrhagic stroke is considered a neurological event and not as a separate bleeding event.


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Right Heart Failure

Symptoms and signs of persistent right ventricular dysfunction [central venous pressure (CVP) > 18 mmHg with a cardiac index <2.0 L/min/m2 in the absence of elevated left atrial/pulmonary capillary wedge pressure (greater than 18 mmhg), tamponade, ventricular arrhythmias or pneumothorax] requiring RVAD implantation; or requiring inhaled nitric oxide or inotropic therapy for a duration of more than 1 week at any time after LVAD implantation.

INTERMACS Protocol 2.3 - Oct 30, 2008

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Right Heart FailureSymptoms and signs of persistent right ventricular dysfunction [central venous pressure (CVP) > 18 mmHg with a cardiac index <2.3 L/min/m2 in the absence of elevated left atrial/pulmonary capillary wedge pressure (greater than 18 mmhg), tamponade, ventricular arrhythmias or pneumothorax] requiring RVAD implantation; or requiring inhaled nitric oxide or inotropic therapy for a duration of more than 1 week at any time after LVAD implantation.” LEVEL OF RIGHT HEART FAILURE

Severe RHF: RVAD

Moderate RHF: Inotrope or intravenous or inhaled pulmonary vasodilator (e.g. prostaglandin E or inhaled nitric oxide)

Mild RHF: Meets 2 of the 4 clinical criteria listed below CVP > 18 mmHg or mean RA pressure > 18 mmHg CI < 2.3 L/min/M2 (by Swan) Ascites or evidence of moderate to worse peripheral edema Evidence of elevated CVP by echo (dilated VC, IVS with collapse), physical exam (signs of increased jugular venous pressure)


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Kaplan-Meier Survival: Device Type

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Pre-Implant Patient Profile LVAD (n=1440) Bi-VAD (n=206)

1 Critical Cardiogenic Shock 380 (26%) 112 (54%

2 Progressive Decline 612 (43%) 78 (38%)

3 Stable but Inotrope dependent 226 (16%) 9 (4%)

4 Recurrent Advanced HF 150 (10%) 4 (2%)

5 Exertion Intolerant 27 (2%) 1 (1%)

6 Exertion Limited 22 (1%) 2 (1%)

7 Advanced NYHA Class III 23 (2%) 0 (0%)

Total 1440 (100%) 216 (100%)

p < .0001

* Total Artificial Heart devices (TAH) are excluded from this table

Adult Primary Implants, n=1706

INTERMACS: June 2006 – September 2009: Bi-VAD Study

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RA Pressure LVAD (n=1440) Bi-VAD (n=206)

< 10 277 (33%) 18 (13%)

10-19 398 (47%) 72 (53%)

20-29 139 (17%) 44 (32%)

30+ 27 ( 3%) 3 (2%)

Total 841 (100%) 137 (100%)

Missing 599/1440 (42%) 69/206 (33%)

Implant dates: June 2006 – September 2009: Bi-VAD Study

All Adult Primary LVADs and BIVADs: n=1646

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HemolysisA plasma-free hemoglobin value that is greater than 40 mg/dl, in association with clinical signs associated with hemolysis (e.g., anemia, low hematocrit, hyperbilirubinemia) occurring after the first 72 hours post-implant. Hemolysis related to documented non-device-related causes (e.g. transfusion or drug) is excluded from this definition.


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MedaMACS

To provide parallel information about medical outcomes for survival, function, and quality of life

within INTERMACS profiles 4-7 to help refine patient selection in the

crucial range of ambulatory HF where the greatest benefit of VAD is

anticipated.

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6MWGait speed

Euroqol+KCCQVAD Survey

EventsRisk ScoresTreatments

BaselineB

MedaMACS Study Timeline

Inpt oroutpt

1 MonthRe-Look Baseline

6 mosPhone

Interview

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18m 2 YrsPhone

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outptA B

CTimeZero

DREVIVE-ITSites (n=6)

Non REVIVE-ITSites (n=6)

Telephone Contact

6MWGait speed

Euroqol+KCCQVAD SurveyRisk Scores

6MWGait speed


EventsTreatments

BaselineA

6MWGait speed


EventsRisk ScoresTreatments

Study Site Phone Calls 6 and 18 mosEvents (hosp, stroke, transplant, vad, inotropes, death)

Meds, Euroqol, NYHA/INTERMACS profile

Onemonth

Consent 1mo. 12mos 24mos

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C2-Yr Visit

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REVIVE-IT

This is a randomized trial of the Heartware Ventricular Assist System (VAS) versus the best medical therapy in patients with advanced heart failure and whose illness is not severe enough to qualify for transplant or permanent left ventricular assist device (LVAD) therapy based on current guidelines

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Coordinator Training Session: March 11, 2012

pediMACS Launch Status

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pediMACS will follow the structure of INTERMACS

A few important changes from INTERMACS: Pediatric patients (< 19 yrs. at time of implant) Includes both durable and temporary support

MCSDs Modifications of AE definitions Possible expansion of quality of life instruments

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IMACS Overview - General

ISHLT Mechanically Assisted Circulatory Support (IMACS) Registry

• International registry to enroll and follow patients receiving durable MCSDs in all countries and hospitals wishing to participate

• TASK: Create, implement, and analyze a registry with high standards for complete enrollment of patients and complete and accurate submission of data

• GOAL: Allow participating centers to engage in outcomes research about MCSDs

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Mission Statement

ISHLT Mechanically Assisted Circulatory Support (IMACS) Registry

The specific mission of IMACS is the promotion of scientific investigations and publications based on analyses of this multinational database, providing the opportunity for an international array of authors to collaborate in Registry investigations, presentations, and publications.

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Documents

Sixth Annual Meeting March 12, 2012 8:00am to 4:00pm Crowne Plaza National Airport Arlington, VA