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Care | Valued | Excellence | Innovation
DCD Heart TransplantationPapworth Perspective
Simon Messer Stephen Large
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Care | Valued | Excellence | Innovation
Objectives
•Heart transplantation in the UK
•DCD donation in the UK
•DCD impact on heart function
•Normothermic Regional Perfusion (NRP)
•Direct Procurement and Perfusion (DPP)
•NRP then cold storage (NRP/CS)
•How do they compare?
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Care | Valued | Excellence | Innovation
UK Heart Transplant Activity
166
154
140 141
157 156
127 128132 130
115120
126131
136 138144 145
204198
2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013 2013-2014
Year
0
50
100
150
200
250
Nu
mb
er
Figure 7.1 Deceased donor heart programme in the UK, 1 April 2004 - 31 March 2014,
Number of donors, transplants and patients on the active transplant list at 31 March
Donors
Transplants
Transplant list
106110
8895 93
126130
169
200
246
NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http//www.odt.nhs.uk/pdf/organ_specific_report_cardiothoracic_2014.pdf
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Care | Valued | Excellence | Innovation
UK Outcomes Following Listing
6 months 1 year 2 years 3 years
Time since listing
0
10
20
30
40
50
60
70
80
90
100
Pe
rce
nta
ge
DiedRemovedStill w aitingTransplanted
Figure 7.3 Post-registration outcome for 87 new non-urgent heart only registrations made in the
UK, 1 April 2010 - 31 March 2011
31
52
13
5
39
37
18
6
45
18
26
10
46
11
30
13
NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http//www.odt.nhs.uk/pdf/organ_specific_report_cardiothoracic_2014.pdf
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Care | Valued | Excellence | Innovation
The Rise of DCD Donation in UK
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Care | Valued | Excellence | Innovation
UK DCD Transplant SuccessDonation 1.1 to 18.3 (pmp)
1.9 to 11.7 (pmp)
0.2 to 2.2 (pmp)
0.5 (pmp)
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Care | Valued | Excellence | Innovation
Messer S, Lannon J, R Axell, Wong E, Hopkinson C, Fielding S, Ali A, Tsui S, Large S
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Care | Valued | Excellence | Innovation
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Care | Valued | Excellence | Innovation
Prior to withdrawal
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Care | Valued | Excellence | Innovation
Start of Functional Warm Ischaemia
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Mechanical Asystole
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Care | Valued | Excellence | Innovation
Nom
oxia
Ano
xia
15 m
ins
60 m
ins
90 m
ins
150
min
s
0
2
4
6
8
10
ATP/ADP Ratio Following Withdrawal and Reperfusion
Time (mins)
AT
P/A
DP
rati
o
NRP
DPP
p=0.75
p=0.75
p=0.57 p=0.47 p=0.88 p=0.06
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Care | Valued | Excellence | Innovation
Techniques of DCD heart retrieval in UK
• Direct Procurement and Perfusion: normothermicmachine perfusion during transportation
• Normothermic Regional Perfusion (NRP) followed by normothermic machine perfusion during transportation
• Normothermic Regional Perfusion (NRP) followed by cold static storage during transportation
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Care | Valued | Excellence | Innovation
Direct Procurement and Perfusion
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Care | Valued | Excellence | Innovation
Direct Procurement and Perfusion
Advantages
•Simple to perform
•No additional blood products
•No additional staff
•No additional equipment
•Easy to teach to others
•Can work with any abdominal retrieval team
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Care | Valued | Excellence | Innovation
Direct Procurement and Perfusion
Drawbacks
•Unable to functionally assess the heart
•Waste 45 000$ for every heart declined on rig
•Completely reliant on Lactate
•Short ischaemic times
•Donor age restricted to 50 years old
•Surgeons uncomfortable when extending the ischaemic time
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Care | Valued | Excellence | Innovation
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Care | Valued | Excellence | Innovation
Rising Lactate on the OCS
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Care | Valued | Excellence | Innovation
Normothermic Regional Perfusion
Death declared
Median Sternotomy
Clamp Arch Vessels
NRP Full Flow/Carotid Doppler
Intubate and Ventilate
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Care | Valued | Excellence | Innovation
60 mins wean from NRP
Swann Ganz / TOE
Cardioplegia
Instrument on OCS
Transplant
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Care | Valued | Excellence | Innovation
Normothermic Regional Perfusion
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Care | Valued | Excellence | Innovation
Normothermic Regional Perfusion Advantages
•Allows a full functional assessment of the heart
•Shorter ischaemic time by 14 minutes
•Allows the surgeon to disregard lactate
•Allows the donor age to be extended
•Allows the ischaemic time to be extended
•Avoids the cost of placing a heart on the OCS that is turned down.
•Allows liver, kidneys, lungs and pancreas to be perfused
•Removes the haste from retrieval and organ damage
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Care | Valued | Excellence | Innovation
Normothermic Regional Perfusion
Drawbacks
•Additional cost of 4500$ per run for equipment
•Ethical concerns of perfusing a cadaver
•Additional blood products- 6 units of packed red cells
•Additional 2 hours in donor hospital
•Additional personnel and equipment
•Retaining skills and training
•Working in collaboration with abdominal retrieval team
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Care | Valued | Excellence | Innovation
NRP and cold storage
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Care | Valued | Excellence | Innovation
NRP and Cold Storage
Advantages
•Functional assessment of donor heart
•No cost of TransMedics OCS
•Donor age can be extended
•Warm ischaemic time can be extended
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Care | Valued | Excellence | Innovation
NRP and Cold Storage
•Drawbacks
•Reliant on donor and recipient co location
•Ethical concerns of perfusing organs within the cadaver
•Additional donor theatre time
•Additional personnel
•Additional equipment
•How long can the heart be cold stored for?
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Care | Valued | Excellence | Innovation
Extending the Boundaries
Donor:
36 year old male ICH
Withdrawal to death 139 minutes
Withdrawal to blood perfusion 149 minutes
After NRP
CI 4.5L/min/m2, CO 8.8L/min, HR 100bpm, CVP 7mmHg
PCWP 6mmHg, MAP 104mmHg, EF 67%
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Care | Valued | Excellence | Innovation
Extending the Boundaries
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Care | Valued | Excellence | Innovation
Extending the Boundaries
Recipient:
51 year old male HVAD
OCS 428 min
Off CPB on 3.8mcg/kg/min Dopamine, 0.05mcg/kg/min Adrenaline
CI 2.5L/min/m2, MAP 64mmHg, CVP 11mmHg
1 day mechanical ventilation
5 days ITU
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Care | Valued | Excellence | Innovation
Outcomes following Heart Transplantation from Donation After Circulatory Determined Death
(DCD) Donors
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Care | Valued | Excellence | Innovation
Aim
• Are the early outcomes of DCD heart transplantation comparable to DBD heart transplants?
• What is the best method to procure the DCD heart?
• Normothermic Regional Perfusion (NRP)
• Direct Procurement and Perfusion (DPP)
• How much can DCD donors increase overall heart transplant activity by?
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Care | Valued | Excellence | Innovation
Method• Single centre observational matched control study
• Comparing
Consecutive DCD heart transplant patients between 01/02/15 to 31/07/16
• Primary Outcome: 90 day survival
• Secondary Outcomes: Mechanical Support, Inotropic Support, Cardiac Performance, ITU duration, Mechanical Ventilation Duration, CVVH requirement, Hospital duration, Rejection Episodes
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Care | Valued | Excellence | Innovation
Method• Matching:
Donor: Age, sex and height
Recipient: Age, sex and height, TPG, PVR, etiology, pre tx mechanical support
• Two retrieval techniques
Normothermic Regional Perfusion (NRP)
Direct Procurement and Perfusion (DPP)
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Care | Valued | Excellence | Innovation
Results
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Care | Valued | Excellence | Innovation
Donor DemographicsDCD vs. DBD NRP vs. DPP
DCD n=21 DBD n=21 NRP n=12 DPP n=9
Age Yrs (MedIQR)) 37 (33-39) 34 (30-36) ns 37 (33-39) 34 (30-36) ns
Male n (%) 18 (86) 14 (67) ns 9 (75%) 9 (100%) ns
Height cm 175 (172-181) 178 (168-183) ns 175(169-180) 175(172-181 ns
Cause of Death
HBI n(%) 9 (42) 4 (19) 0.04 2 (17) 7 (78) 0.01
ICH n (%) 6 (29) 9 (43) 6 (50) 0 (0)
TBI n (%) 5 (24) 2 (10) 3 (25) 2 (22)
Other n (%) 1 (5) 6 (29) 1 (8) 0 (0)
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Care | Valued | Excellence | Innovation
Recipient DemographicsDCD vs. DBD NRP vs. DPP
DCD n=21 DBD n=21 NRP n=12 DPP n=9
Age years Med(IQR) 58 (49-61) 59 (60-61) ns 59 (54-62) 50 (42-60) ns
Male n (%) 18 (86) 18 (86) ns 10 (83) 8 (89) ns
Height (cm) 174 (171-178) 173 (167-179) ns 174(169-175) 176(172-181) ns
TPG (mmHg) 7 (5-8) 7 (4-8) ns 8 (7-8) 6 (4-6) ns
PVR (Wood Units) 1.9 (1.4-2.2) 1.9 (1.5-2.4) ns 2.0 (1.7-2.2) 1.5 (1.3-2.1) ns
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Care | Valued | Excellence | Innovation
Recipient DemographicsDCD vs. DBD NRP vs. DPP
DCD n=21 DBD n=21 NRP n=12 DPP n=9
Pre Tx VAD n (%) 4 (19) 4 (19) ns 1 (8) 3 (33) ns
Aetilogy
DCM (%) 12 (57) 12 (57) ns 9 (75) 3 (33) ns
HCM n (%) 5 (23) 3 (14) 2 (17) 3 (33)
RCM n (%) 0 (0) 2 (10) 0 (0) 0 (0)
IHD n (%) 2 (10) 3 (14) 0 (0) 2 (22)
VHD n (%) 1 (5) 1 (5) 1 (8) 0 (0)
ARVC n (%) 1 (5) 0 (0) 0 (0 1 (11)
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Care | Valued | Excellence | Innovation
Ischaemic Timings NRP/DPP
Time Median (IQR) NRP n=12 DPP n=9 P value
Withdrawal to death (mins) 18 (13-21) 19 (15-23) ns
Donation Withdrawal Ischaemic Time (mins) 24 (21-28) 38 (32-43) 0.005
Functional Warm Ischaemic Time (mins) 18 (15-20) 26 (23-31) 0.002
NRP Duration (mins) 41 (33-52) - -
OCS Perfusion Time (mins) 170 (140-
179)
280 (206-
308)
0.02
Implant Duration (mins) 32 (31-38) 36 (33-44) ns
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Care | Valued | Excellence | Innovation
OutcomesDCD vs. DBD NRP vs. DPP
DCD n=21 DBD n=21 NRP n=12 DPP n=9
Survival
30 day survival n (%) 21 (100) 21 (100) ns 12 (100) 9 (100) ns
90 Day survival n (%) 20 (95) 20 (95) ns 12 (100) 8 (89) ns
Mechanical Support ns
IABP n (%) 5 (24) 2 (10) ns 2 (17) 3 (33) ns
ECMO n (%) 2 (10) 1 (5) ns 1 (8) 1 (11) ns
VAD n (%) 1 (5) 0 (0) ns 0 (0) 1 (11) ns
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Care | Valued | Excellence | Innovation
Cardiac Performance ITUDCD vs. DBD NRP vs. DPP
Inotropic Support DCD n=21 DBD n=21 NRP n=12 DPP n=9
Dopamine (mcg/kg/min) 4.2 4.5 0.05 4.7 3.2 ns
Adrenaline (mcg/kg/min) 0.05 0.05 ns 0.04 0.05 ns
Noradrenaline (mcg/kg/min) 0.00 0.04 ns 0.00 0.01 ns
Cardiac Performance
Cardiac Index (L/min/m2) 2.5 (2.3-2.7) 1.9 (1.8-2.4) 0.01 2.5 (2.3-2.7) 2.5 (1.7-2.7) ns
Cardiac Output (L/min) 4.7 (4.2-5.2) 3.8 (3.2-4.2) 0.002 4.9 (4.3-5.1) 4.6 (3.6-6.5) ns
MAP mmHg 72 (64-81) 65 (58-69) 0.04 72 (64-81) 74 (66-79) ns
CVP mmHg 9 (8-10) 10 (8-12) ns 10 (8-11) 9 (7-10) ns
PAD mmHg 14 (12-17) 15 (12-18) ns 14 (13-16) 16 (13-18) ns
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Care | Valued | Excellence | Innovation
OutcomesDCD vs. DBD NRP vs. DPP
DCD n=21 DBD n=21 NRP n=12 DPP n=9
Ventilation Duration (days) 0.6 (0.5-1.5) 2.1 (0.9-2.5) 0.05 0.6(0.4-1.1.1) 0.6(0.5-4.0) ns
CVVH n (%) 5 (24) 6 (29) ns 3 (25) 2 (22) ns
ITU Duration (days) 5 (3-5) 7 (6-9) 0.02 5 (4-5) 3 (3-7) ns
Hospital Duration (days) 19 (17-26) 27 (19-34) ns 20 (18-27) 19(16-23) ns
Rejection n (%) 9 (43) 13 (62) ns 4 (33) 5 (56) ns
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Care | Valued | Excellence | Innovation
Newcastle Papworth Harefield Birmingham Manchester Glasgow
Transplant centre
0
10
20
30
40
50
60
No
. o
f tr
an
sp
lan
ts
DCDDBD
Figure 5.3 Number of adult heart transplants in the UK, 1 April 2015 to 31 March 2016,
by transplant centre
22
36
15
21
4
2629
7
Source: Annual Report on Cardiothoracic Transplantation 2015/16, NHS Blood and Transplant
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Care | Valued | Excellence | Innovation
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Care | Valued | Excellence | Innovation
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Care | Valued | Excellence | Innovation
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Care | Valued | Excellence | Innovation
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Care | Valued | Excellence | Innovation
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Summary
NRP reduces ischaemic time
Allows donor age to be extended
No longer reliant on Lactate
Allows organ function to be optimised
No difference in clinical outcomes in our series NRP/DPP
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Care | Valued | Excellence | Innovation