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Care | Valued | Excellence | Innovation

DCD Heart TransplantationPapworth Perspective

Simon Messer Stephen Large


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?


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


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


The Rise of DCD Donation in UK


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)


Messer S, Lannon J, R Axell, Wong E, Hopkinson C, Fielding S, Ali A, Tsui S, Large S


Prior to withdrawal


Start of Functional Warm Ischaemia


Mechanical Asystole


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


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


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



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


Rising Lactate on the OCS


Normothermic Regional Perfusion

Death declared

Median Sternotomy

Clamp Arch Vessels

NRP Full Flow/Carotid Doppler

Intubate and Ventilate


60 mins wean from NRP

Swann Ganz / TOE

Cardioplegia

Instrument on OCS

Transplant


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



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


NRP and cold storage


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


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?


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%



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


Outcomes following Heart Transplantation from Donation After Circulatory Determined Death

(DCD) Donors


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?


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


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)


Results


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)


Recipient DemographicsDCD vs. DBD NRP vs. DPP


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


Recipient DemographicsDCD vs. DBD NRP vs. DPP


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)


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


OutcomesDCD vs. DBD NRP vs. DPP


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


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


OutcomesDCD vs. DBD NRP vs. DPP


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


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


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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