A Heart for Everyone in Need

Jason W. Smith, MD2016 Donation andTransplantation SymposiumSeattle, WA

The Scope of the Problem

• 915,000 new cases/year

• 1.1 million hospitalizations/yr

• 5.7 million patients with CHF, rising to 8

million by 2030

• 300,122 deaths in 2013

Mozaffarian et al. Circulation. 2016; 133(4): e38-e360

Prevalence of heart failure by sex and age (National Health and Nutrition Examination Survey: 2009–2012).

Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360

Copyright © American Heart Association, Inc. All rights reserved.

Improving Survival in LVAD Trials

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HM II DT Slaughter NEJM 2009

HM II BTT Pagani JACC 2009

HM II BTT Starling HFSA 2009

VE DT LVAD REMATCH Rose NEJM 2001

XVE DT LVAD Slaughter NEJM 2009

OMM REMATCH Rose NEJM 2001OMM INTrEPID Rogers JACC 2007

Novacor DT LVAD INTrEPID Rogers JACC 2007

Increasing MCS use

The Journal of Heart and Lung Transplantation, Volume 34, Issue 12, 2015, 1495–1504

Long-Term LVAD Survival

The Journal of Heart and Lung Transplantation, Volume 34, Issue 10, 2015, 1244–1254

Kaplan-Meier long-term survival by era

Two Decades of Stability

J Heart Lung Transplant, vol 33, 2014

Suicide Rate in the US by Year

CDC. Web-based Injury Statistics Query and Reporting System (WISQARS). Atlanta, GA. 2013

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What can we do?

• Improve the utilization of hearts

• Bring new hearts into the system, go farther

• Increase the use of expanded criteria hearts

• Use hearts from donors declared by circulatory death criteria

Systematic Review

Our Challenge

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UW Heart Ischemia

Flight Times From SeattleSan Jose, CA 2

Walnut Creek, CA 2Henderson, NV 2.3Las Vegas, NV 2.5

Regina, Saskatchewan 2.5La Jolla, CA 2.7

San Diego, CA 2.7Loveland, CO 2.8Rapid City, SD 2.8

Phoenix, AZ 3Tucson, AZ 3.3El Paso, TX 3.5

Anchorage, AK 3.5Lincoln, NE 3.7

Minneapolis, MN 4Dallas, TX 4.5Plano, TX 4.5

Chicago, IL 4.8Peoria, IL 4.8

San Jose

Loveland

Rapid City

Tucson

PeoriaLincoln

Traditional Approach

• Cardioplegic Arrest

• 4 degrees Celcius flush

• Packed in Iced slurry

• Transported in cooler

• Outside limit 4-6 hours

• Total flight time 2-3hours.

Ex-Vivo Heart Perfusion

OCS Heart Device Heart Perfusion Module Maintenance Solution Set

PROCEED Provided the Foundation to Prove Safety & Effectiveness in Routine Donor Heart Preservation

Harefield Successful Experience with Extended Donor/Recipient Conditions Using OCS Heart

OCS™ EXPAND Heart Was Initiated To Develop a US

Experience with OCS™ in Extended Criteria Donor Hearts

OCS EXPAND Trial

• Background: The only FDA IDE approved pivotal trial focusing on improving utilization of unutilized donor hearts in the U.S.

• Trial Design: Initially, single arm trial and transition to a comparison trial

• Primary Endpoint: Composite of short-term survival and freedom from primary graft dysfunction in the initial post-transplant period

Recipient Eligibility Criteria

INCLUSION EXCLUSION

Listed for heart transplant Age ≥18 years old Signed: written informed

consent document

Prior solid organ or bone marrow transplant

Chronic use of hemodialysis or diagnosis of chronic renal insufficiency

Multi-organ transplant

Donor Eligibility CriteriaINCLUSION EXCLUSION

Cross-clamp ≥ 4 hours Cross-clamp ≥ 2 hours plus

Donor age ≥ 55 yo; Donor age 45-55 yo w/ no

LHC LVH CPR ≥ 20 min EF≥40 ≤50%; Donor angiogram CAD History of CO poisoning History of DM II

CAD with ≥50% stenosis Cardiogenic shock or

myocardial infarction Sustained terminal EF of

<40% Significant valve disease

except for competent bicuspid aortic valve

Current Trial Centers

West Coast Trial Centers

First Nine EXPAND Hearts

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Indications for OCS

• Clamp > 4 Hours 4

• Prolonged CPR 2

• LVH 1

• Low Ejection Fraction 2

Donor Case

• 41 yo Male neck injury

• 35 minutes of CPR

• Ejection Fraction 50%

• LVH 1.4 cm PW and 1.3 SW

• 25 pack-year smoking

• Angiogram with nl coronaries

DCD Donor Process

The First DCD Heart TransplantDr ChristiaanBarnard

The Annals of Thoracic Surgery Vol 37 No 3 March 1984

Stole the Thunder from …

Dr. Norman Shumway

Where is the action today?

Dr. Kumud Dhital

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Successful clinical series of DCD Heart Transplantation using OCS Heart Platform• Sydney Australia: 9 successful transplants• Papworth Hospital, UK 20• Harefield Hospital, UK 11

Successful DCD Heart Transplants To date, N=40

DCD Heart - Sydney

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DCD Heart Tx in the US

UW Effort in DCD Heart Tx

• 3 Phase Project

– Phase 1

• Participate in DCD retrieval process

• Establish timelines and feasibility

• Develop a workable protocol

OR Set up for DCD Procurement

– Phase 2

• Retrieve DCD hearts for a 4 hour perfusion run on OCS

• Develop metabolic and echo assessment tools

• Assess histology of DCD vs BD hearts to confirm usability

3D Strain Imaging

Gene Array Analysis

DCD Heart

• 54 yo Male

• Hx of hypertension

• CVA

• WDLS to Reperfusion 73

minutes

• Agonal phase to

Reperfusion 38 minutes

– Phase 3

• Apply established criteria to DCD in the NW for a clinical DCD heart trial.

• Either as a single/multiple institution investigator initiated trial

• Or, as an industry initiated IDE

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DCD Hearts in the US 2005-2015

Estimates of usable DCD hearts12%-38% = 180-570 additional hearts tomorrow

Advantages

• High Volume DCD region

• Heparin administration well accepted

• Close working relationship with OPO

• Support of centers already performing DCDs

• Leading EXPAND trial enrollment

Challenges

• Cultural resistance to change

• Very risk averse atmosphere

• No FDA approved device available

Next Steps

• Donation after Circulatory Death

• More Exact HLA matching

• Immune Silencing

• Stem Cell Therapy

HLA Matching

The Journal of Heart and Lung Transplantation, Volume 25, Issue 9, 2006, 1057–1062

Distribution of HLA Matching in Pediatric Heart Transplant

HLA Matching in OHT

Jarcho et al. JHLT July/August 1994

The Journal of Heart and Lung Transplantation, Volume 25, Issue 9, 2006, 1057–1062

HLA – DR Matching in Pediatric Heart Transplant

Our Village