a heart for everyone in need
TRANSCRIPT
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 BTT Miller NEJM 2007
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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UW Active Waitlist Vol
Waitlist Vol
Linear (Waitlist Vol)
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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Total Organ Ischemic Time
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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Time from X-clamp to X-clamp
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