1 hearts what makes an allograft marginal & methods of evaluation: hearts steven sl tsui...

11

What makes an allograft marginal & Methods of

evaluation: HeartsHearts

Steven SL TsuiSteven SL TsuiDirector of Transplantation,Director of Transplantation,

Papworth Hospital, Cambridge, U.K.Papworth Hospital, Cambridge, U.K.

British Transplant Society Congress 2010Pre-congress Clinical Symposium

Tuesday 16th March 2010

Papworth HospitalNHS Foundation Trust

NHS

http://www.bts.org.uk/

22

Heart TransplantHeart Transplant


NHS

19671st successful HTx


1990199019801980 2000200019701970 20102010

19791st successful UK HTx


StandardDonor Criteria


33

NUMBER OF HEART TRANSPLANTSNUMBER OF HEART TRANSPLANTS REPORTED BY YEARREPORTED BY YEAR

189 318665

1182

2159

2713

31363363

40034171 4203

4364 4429 4396 4263 41993864

3581 3433 3390 3283 3226 3065 3185 3205

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Nu

mb

er

of

Tra

ns

pla

nts

ISHLT

2008NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has declined in recent years. J Heart Lung Transplant 2008;27: 937-983

44



NHS



1990199019801980 2000200019701970 20102010





55



NHS



1990199019801980 2000200019701970 20102010





Older DonorsOlder Donors

LongerIschaemicTimes

LongerIschaemicTimes

Valve RepairValve Repair

Hep C+VEHep C+VE

LV HypertrophyLV Hypertrophy

CoronaryDiseaseCoronaryDisease

NHBDNHBD

Drug AbuseDrug Abuse

Brain MalignancyBrain Malignancy

CardiacArrestCardiacArrest

PoisonPoison

66

Heart Transplant Rates Heart Transplant Rates 20062006

7.4

6.9 6.8

6.1 6.1 6

5.55 5

4.4

3.83.5 3.5 3.4 3.2

2.92.6 2.5 2.4 2.2 2

0.90.6 0.6

0.30

1

2

3

4

5

6

7

8

He

art

Tx

pe

r m

illio

n p

op

ula

tio

n

Belgi

um

Austria

Norway

Fran

ce

Spain

Italy

Czech

German

y

Denm

ark

Sweden

Portugal

Slove

nia

Switzer

land

Finl

and

Croat

ia

Lith

uani

aUK

Poland

Nether

lands

Hungar

y

Slova

kia

Latv

ia

Greec

e

Turk

ey

Roman

ia


NHS

2009 UK Heart Transplant Rate

77

Variations in Variations in Heart Transplant RatesHeart Transplant Rates

Heart donation rateHeart donation rate Yield rate:Yield rate:

19% to 62% (mean 39%)19% to 62% (mean 39%)11

Donor cause of deathDonor cause of death Donor ageDonor age Threshold for using marginal organsThreshold for using marginal organs

Even in the most aggressive program, a significant % of Even in the most aggressive program, a significant % of donated hearts are not transplanteddonated hearts are not transplanted

1 1999 survey by Assoc. of Organ Procurement Organizations (AOPO)


NHS

88

GRAFT FAILURE42%

CARDIAC ALLOGRAFT VASCULOPATHY

ACUTE REJECTION

LYMPHOMA

MALIGNANCY, OTHER

CMV

INFECTION, NON-CMV

GRAFT FAILURE

TECHNICAL

OTHER

MULTIPLE ORGAN FAILURE

RENAL FAILURE

PULMONARY

CEREBROVASCULAR

ADULT HEART TRANSPLANT ADULT HEART TRANSPLANT RECIPIENTS: RECIPIENTS:

Cause of Death Cause of Death (Deaths: January 1992 - June 2006)(Deaths: January 1992 - June 2006)

ISHLT 2008J Heart Lung Transplant 2008;27: 937-983


NHS

99

Definition of High Risk Donor (HRD):Definition of High Risk Donor (HRD): Donor age > 40 yrDonor age > 40 yr High dose inotropes (dopamine > 12 High dose inotropes (dopamine > 12 μμg.kgg.kg-1-1.min.min-1 -1 )) CPR > 5 minutesCPR > 5 minutes Elevated CK-MBElevated CK-MB D/R weight ratio < 80%D/R weight ratio < 80% Wall motion abnormalityWall motion abnormality Rhythm disturbancesRhythm disturbances Total ischemic time > 5 hrsTotal ischemic time > 5 hrs

HRD accounted for HRD accounted for 38.3%38.3% of 188 heart of 188 heart transplants between 1985-92 in Oregontransplants between 1985-92 in Oregon

A 1994 Definition of A 1994 Definition of Marginal Donor HeartMarginal Donor Heart

Ott et al. Ann Thorac Surg 1994;57:76-82


NHS

1010

Definition of Marginal Donor:Definition of Marginal Donor: Donor age > 55 yearsDonor age > 55 years cocaine or intravenous drug usecocaine or intravenous drug use diabetes mellitusdiabetes mellitus hepatitis C +vehepatitis C +ve EF < 45%EF < 45% D:R weight ratio < 0.7D:R weight ratio < 0.7

UNOS Jan 1999 – Dec 2005: 13,024 heart UNOS Jan 1999 – Dec 2005: 13,024 heart transplantstransplants

Marginal donors, Marginal donors, 10.2% of all Heart Tx in USA10.2% of all Heart Tx in USA

A 2009 Definition of A 2009 Definition of Marginal Donor HeartMarginal Donor Heart

Russo et al. Ann Thorac Surg 2009;87:1066–71


NHS

1111

ADULT HEART TRANSPLANTS ADULT HEART TRANSPLANTS (1/2002-6/2006)(1/2002-6/2006) Relative Risk of 1 Year Mortality with 95% Confidence LimitsRelative Risk of 1 Year Mortality with 95% Confidence Limits

Donor AgeDonor Age

0

0.5

1

1.5

2

2.5

15 20 25 30 35 40 45 50 55 60

Donor Age

p < 0.0001

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

2008ISHLT (N=8,823)J Heart Lung Transplant 2008;27: 937-983

1212


Donor BMIDonor BMI

0

0.5

1

1.5

18 20 22 24 26 28 30 32 34

Donor BMI (kg/m2)

p = 0.0288

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity


1313


Ischemia TimeIschemia Time

0

0.5

1

1.5

2

30 60 90 120 150 180 210 240 270 300 330 360

Ischemia Time (minutes)

p = 0.0060Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity


1414

ADULT HEART TRANSPLANTSADULT HEART TRANSPLANTS (1/2002-(1/2002-6/2006) 6/2006)

Factors Factors NotNot Significant for 1 Year Mortality Significant for 1 Year Mortality

Recipient Factors: Prior malignancy, gender, hospitalized, prior pregnancy, balloon pump, diabetes, PRA

Donor Factors: Clinical infection, history of diabetes, gender, history of hypertension, cause of death, history of malignancy

Transplant Factors: HLA mismatch, CMV mismatch, prior transplant

2008ISHLT J Heart Lung Transplant 2008;27: 937-983

1515

Organs that fail to meet 1 or more of the Organs that fail to meet 1 or more of the traditional criteria for an optimal cardiac traditional criteria for an optimal cardiac donordonor

Consensus Conference Consensus Conference Definition of Marginal Donor Definition of Marginal Donor

HeartHeart

1 Zaroff et al. Circulation. 2002;106:836-841


NHS

1616

Extra Cardiac FactorsExtra Cardiac Factors

Donor age < 55 y.o.Donor age < 55 y.o. Donor medical historyDonor medical history

Recent cardiac arrest Recent cardiac arrest Hep C +veHep C +ve Risk of coronary disease: smoking, hypertension, Risk of coronary disease: smoking, hypertension,

diabetes, lipidsdiabetes, lipids Donor lifestyleDonor lifestyle

Cocaine useCocaine use IV drug abuseIV drug abuse Unprotected sex/multiple partnersUnprotected sex/multiple partners

Donor/recipient size mismatchDonor/recipient size mismatch


NHS

1717

Structural AbnormalitiesStructural Abnormalities

Coronary artery diseaseCoronary artery disease LV hypertrophyLV hypertrophy Valvular abnormalityValvular abnormality Congenital lesionsCongenital lesions

Bicuspid AVBicuspid AV Secundum ASDSecundum ASD


NHS

1818

Functional AbnormalitiesFunctional Abnormalities

EchocardiogramEchocardiogram EF > 45%EF > 45%

Hemodynamic targetsHemodynamic targets CVP CVP < 12 mmHg< 12 mmHg PCWP PCWP < 12 mmHg < 12 mmHg MAP MAP > 60 mmHg> 60 mmHg C.I.C.I. > 2.4 L.min> 2.4 L.min-1-1.m.m-2-2

SVRSVR 800 – 1200 dyne.sec800 – 1200 dyne.sec-1-1.cm.cm-5-5

Dopamine/dobutamine > 10 Dopamine/dobutamine > 10 μμg.kgg.kg-1-1.min.min-1-1


NHS

1919

Donor Heart AssessmentDonor Heart Assessment

BiochemicalBiochemical StructuralStructural

ECG ECG EchocardiogramEchocardiogram Coronary angiogramCoronary angiogram

Functional Functional EchocardiogramEchocardiogram Invasive monitoringInvasive monitoring


NHS

2020

Biochemical MarkersBiochemical Markers

CK-MBCK-MB TroponinTroponin

Anderson et al. Transplantation. 1994;58:1056-57 Vijay et al. Ann Thorac Surg. 1998;66:1934-39

Pro-calcitoninPro-calcitonin Venkateswaran et al. Transplantation. 2009;88:582-8

TNF-alphaTNF-alpha SMARCAL-1SMARCAL-1

Aharinejad et al. Circulation. 2009;120:S198-205


NHS

2121

Structural AssessmentStructural Assessment

ECG criteriaECG criteria S in V1 + R in V5/V6 > 35 mm

EchocardiogramEchocardiogram Posterior wall or septum > 12 mmPosterior wall or septum > 12 mm

Associated risk factors:Associated risk factors: History of hypertensionHistory of hypertension Ischaemic time > 180 min.Ischaemic time > 180 min.

1 Marelli et al. J Heart Lung Transplant. 2000;19:496-503


NHS

2222

Coronary AngiographyCoronary Angiography

1 1 Recommended: Recommended: Male Male > 45 yr> 45 yr FemaleFemale > 50 yr> 50 yr

Consider in > 35 y.o. if Consider in > 35 y.o. if cocaine use cocaine use >2 risk factors>2 risk factors

22 Bench coronary cine-angiography Bench coronary cine-angiography1 Zaroff et al. Circulation. 2002;106:836-8412 Robiscek et al. JTCVS 1992;102:490-5

Hypertension Diabetes Smoking

Dyslipidemia Family history of CAD


NHS

2323

Functional AssessmentFunctional Assessment

Serial echocardiogramSerial echocardiogram Stress echocardiogram Stress echocardiogram 11

DipyridamolDipyridamol DobutamineDobutamine

Invasive hemodynamic assessmentInvasive hemodynamic assessment

1 Leone et al. J Heart Lung Transplant. 2009;28:1141-9


NHS

2424

Hemodynamic MonitoringHemodynamic Monitoring

Swan-Ganz provides:Swan-Ganz provides: PreloadPreload - CVP / - CVP /

PCWPPCWP AfterloadAfterload - SVR- SVR

Cardiac output Cardiac output trendstrends


NHS

Wheeldon et al. J Heart Lung Transplant 1995;14:734-8 Venkateswaran et al. Eur Heart J 2009;30:1771-80

2525

Principles of Donor Principles of Donor Resuscitation:Resuscitation:

Papworth ProtocolPapworth Protocol Achieve isovolaemiaAchieve isovolaemia Acid-base balance Acid-base balance

Powner et al. Prog Transplant 2000;10:25Powner et al. Prog Transplant 2000;10:25

Minimise catecholamine Minimise catecholamine Hormone replacement Hormone replacement

Novitzky et al. Transplantation. 1987;43:852-9

Vasopressin for: Vasopressin for: Pennefather et al. Transplantation Pennefather et al. Transplantation 1990;49:3111990;49:311

diabetes insipidusdiabetes insipidus vascular tonevascular tone

Wheeldon et al. J Heart Lung Transplant 1995;14:734-8Zaroff et al. Circulation. 2002;106:836-41


NHS

2626

“……“…….. it makes little sense to replace .. it makes little sense to replace one diseased heart with another.”one diseased heart with another.”

N. DePasquale N. DePasquale

Editorial: how normal is the donor heart?Editorial: how normal is the donor heart?

Am Heart J 1969;77:719Am Heart J 1969;77:719

…………………….unless it can confer significant .unless it can confer significant prognostic benefit to the recipient.prognostic benefit to the recipient.


NHS

2828

The Alternate Recipient List for The Alternate Recipient List for Heart TransplantHeart Transplant

1 Laks et al. J Heart Lung Transplant. 1997;16:735-42

Standard Donor Heart

Marginal Donor Heart

Status 1 Patient

Status 2 Patient

Status 1 Patient

Alternate Recipient since

1992


NHS

3030

ADULT HEART TRANSPLANT RECIPIENTS: ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death Cause of Death (Deaths: January 1992 - June 2006)(Deaths: January 1992 - June 2006)

CAUSE OF DEATHCAUSE OF DEATH 0-30 Days 0-30 Days

(N = (N = 3,006)3,006)

31 Days – 31 Days –

1 Year1 Year

(N = (N = 2,722)2,722)

>1 Year – >1 Year –

3 Years 3 Years

(N = (N = 2,135)2,135)

>3 Years – >3 Years –

5 Years 5 Years

(N = 1,857)(N = 1,857)


10 Years10 Years

(N = (N = 4,054)4,054)

>10 Years>10 Years

(N = 2,107)(N = 2,107)

CARDIAC ALLOGRAFT CARDIAC ALLOGRAFT VASCULOPATHYVASCULOPATHY 52 (1.7%)52 (1.7%) 127 (4.7%)127 (4.7%) 298 298

(14.0%)(14.0%) 299 (16.1%)299 (16.1%) 581 581 (14.3%)(14.3%) 309 (14.7%)309 (14.7%)

ACUTE REJECTIONACUTE REJECTION 193 (6.4%)193 (6.4%) 338 338 (12.4%)(12.4%)

220 220 (10.3%)(10.3%) 82 (4.4%)82 (4.4%) 69 (1.7%)69 (1.7%) 26 (1.2%)26 (1.2%)

LYMPHOMALYMPHOMA 2 (0.1%)2 (0.1%) 54 (2.0%)54 (2.0%) 85 (4.0%)85 (4.0%) 96 (5.2%)96 (5.2%) 195 (4.8%)195 (4.8%) 73 (3.5%)73 (3.5%)

MALIGNANCY, OTHERMALIGNANCY, OTHER 1 (0.0%)1 (0.0%) 57 (2.1%)57 (2.1%) 218 218 (10.2%)(10.2%) 340 (18.3%)340 (18.3%) 749 749

(18.5%)(18.5%) 392 (18.6%)392 (18.6%)

CMVCMV 4 (0.1%)4 (0.1%) 34 (1.2%)34 (1.2%) 16 (0.7%)16 (0.7%) 3 (0.2%)3 (0.2%) 5 (0.1%)5 (0.1%) 1 (0.0%)1 (0.0%)

INFECTION, NON-CMVINFECTION, NON-CMV 393 393 (13.1%)(13.1%)

896 896 (32.9%)(32.9%)

276 276 (12.9%)(12.9%) 180 (9.7%)180 (9.7%) 442 442

(10.9%)(10.9%) 213 (10.1%)213 (10.1%)

GRAFT FAILUREGRAFT FAILURE 1,257 1,257 (41.8%)(41.8%) 500 (18.4%)500 (18.4%) 499 (23.4%)499 (23.4%) 379 (20.4%)379 (20.4%) 765 (18.9%)765 (18.9%) 353 (16.8%)353 (16.8%)

TECHNICALTECHNICAL 233 (7.8%)233 (7.8%) 28 (1.0%)28 (1.0%) 17 (0.8%)17 (0.8%) 17 (0.9%)17 (0.9%) 36 (0.9%)36 (0.9%) 20 (0.9%)20 (0.9%)

OTHEROTHER 162 (5.4%)162 (5.4%) 175 (6.4%)175 (6.4%) 187 (8.8%)187 (8.8%) 147 (7.9%)147 (7.9%) 339 (8.4%)339 (8.4%) 175 (8.3%)175 (8.3%)

MULTIPLE ORGAN MULTIPLE ORGAN FAILUREFAILURE

356 356 (11.8%)(11.8%) 268 (9.8%)268 (9.8%) 117 (5.5%)117 (5.5%) 102 (5.5%)102 (5.5%) 309 (7.6%)309 (7.6%) 190 (9.0%)190 (9.0%)

RENAL FAILURERENAL FAILURE 20 (0.7%)20 (0.7%) 25 (0.9%)25 (0.9%) 36 (1.7%)36 (1.7%) 65 (3.5%)65 (3.5%) 225 (5.6%)225 (5.6%) 173 (8.2%)173 (8.2%)

PULMONARYPULMONARY 133 (4.4%)133 (4.4%) 108 (4.0%)108 (4.0%) 96 (4.5%)96 (4.5%) 85 (4.6%)85 (4.6%) 172 (4.2%)172 (4.2%) 99 (4.7%)99 (4.7%)

CEREBROVASCULARCEREBROVASCULAR 200 (6.7%)200 (6.7%) 112 (4.1%)112 (4.1%) 70 (3.3%)70 (3.3%) 62 (3.3%)62 (3.3%) 167 (4.1%)167 (4.1%) 83 (3.9%)83 (3.9%)

ISHLT

Last updated based on data as of December 2006 J Heart Lung Transplant 2008;27: 937-983

3131

ADULT HEART TRANSPLANT RECIPIENTS: ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death Cause of Death (Deaths: January 1992 - June 2006)(Deaths: January 1992 - June 2006)

CAUSE OF DEATHCAUSE OF DEATH 0-30 Days 0-30 Days

(N = (N = 3,006)3,006)

31 Days – 31 Days –

1 Year1 Year

(N = (N = 2,722)2,722)

>1 Year – >1 Year –

3 Years 3 Years

(N = (N = 2,135)2,135)


5 Years 5 Years

(N = 1,857)(N = 1,857)


10 Years10 Years

(N = (N = 4,054)4,054)

>10 Years>10 Years

(N = 2,107)(N = 2,107)

CARDIAC ALLOGRAFT CARDIAC ALLOGRAFT VASCULOPATHYVASCULOPATHY 52 (1.7%)52 (1.7%) 127 (4.7%)127 (4.7%) 298 298

(14.0%)(14.0%) 299 (16.1%)299 (16.1%) 581 581 (14.3%)(14.3%) 309 (14.7%)309 (14.7%)

ACUTE REJECTIONACUTE REJECTION 193 (6.4%)193 (6.4%) 338 338 (12.4%)(12.4%)

220 220 (10.3%)(10.3%) 82 (4.4%)82 (4.4%) 69 (1.7%)69 (1.7%) 26 (1.2%)26 (1.2%)

LYMPHOMALYMPHOMA 2 (0.1%)2 (0.1%) 54 (2.0%)54 (2.0%) 85 (4.0%)85 (4.0%) 96 (5.2%)96 (5.2%) 195 (4.8%)195 (4.8%) 73 (3.5%)73 (3.5%)

MALIGNANCY, OTHERMALIGNANCY, OTHER 1 (0.0%)1 (0.0%) 57 (2.1%)57 (2.1%) 218 218 (10.2%)(10.2%) 340 (18.3%)340 (18.3%) 749 749

(18.5%)(18.5%) 392 (18.6%)392 (18.6%)

CMVCMV 4 (0.1%)4 (0.1%) 34 (1.2%)34 (1.2%) 16 (0.7%)16 (0.7%) 3 (0.2%)3 (0.2%) 5 (0.1%)5 (0.1%) 1 (0.0%)1 (0.0%)

INFECTION, NON-CMVINFECTION, NON-CMV 393 393 (13.1%)(13.1%)

896 896 (32.9%)(32.9%)

276 276 (12.9%)(12.9%) 180 (9.7%)180 (9.7%) 442 442

(10.9%)(10.9%) 213 (10.1%)213 (10.1%)

GRAFT FAILUREGRAFT FAILURE 1,257 1,257 (41.8%)(41.8%) 500 (18.4%)500 (18.4%) 499 (23.4%)499 (23.4%) 379 (20.4%)379 (20.4%) 765 (18.9%)765 (18.9%) 353 (16.8%)353 (16.8%)

TECHNICALTECHNICAL 233 (7.8%)233 (7.8%) 28 (1.0%)28 (1.0%) 17 (0.8%)17 (0.8%) 17 (0.9%)17 (0.9%) 36 (0.9%)36 (0.9%) 20 (0.9%)20 (0.9%)

OTHEROTHER 162 (5.4%)162 (5.4%) 175 (6.4%)175 (6.4%) 187 (8.8%)187 (8.8%) 147 (7.9%)147 (7.9%) 339 (8.4%)339 (8.4%) 175 (8.3%)175 (8.3%)

MULTIPLE ORGAN MULTIPLE ORGAN FAILUREFAILURE

356 356 (11.8%)(11.8%) 268 (9.8%)268 (9.8%) 117 (5.5%)117 (5.5%) 102 (5.5%)102 (5.5%) 309 (7.6%)309 (7.6%) 190 (9.0%)190 (9.0%)

RENAL FAILURERENAL FAILURE 20 (0.7%)20 (0.7%) 25 (0.9%)25 (0.9%) 36 (1.7%)36 (1.7%) 65 (3.5%)65 (3.5%) 225 (5.6%)225 (5.6%) 173 (8.2%)173 (8.2%)

PULMONARYPULMONARY 133 (4.4%)133 (4.4%) 108 (4.0%)108 (4.0%) 96 (4.5%)96 (4.5%) 85 (4.6%)85 (4.6%) 172 (4.2%)172 (4.2%) 99 (4.7%)99 (4.7%)

CEREBROVASCULARCEREBROVASCULAR 200 (6.7%)200 (6.7%) 112 (4.1%)112 (4.1%) 70 (3.3%)70 (3.3%) 62 (3.3%)62 (3.3%) 167 (4.1%)167 (4.1%) 83 (3.9%)83 (3.9%)

ISHLT

Last updated based on data as of December 2006 J Heart Lung Transplant 2008;27: 937-983

1 hearts what makes an allograft marginal & methods of evaluation: hearts steven sl tsui...

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