1. EARLY GRAFT FAILURE AFTER HEART TRANSPLANT:
RISK FACTORS AND IMPLICATIONS FOR IMPROVED
DONOR/RECIPIENT MATCHING
C Amarelli1, L S De Santo2, C Marra1, C Maiello1,
C Bancone3, A. Della Corte3, G Nappi3, GP Romano1
No conflict of interest to declare

2. Background
• Early graft failure (EGF) is the most dreaded
complication after heart transplant (Htx).
• Few studies, predominantly multiistitutionals registry
analyses, investigate risk factors and outcome of EGF.
Determinants of early graft failure following heart transplantation, a
10-year, multi-institutional, multivariable analysis.
Young JB, Hauptman PJ, Naftel DC, Ewald G, Aaronson K, Dec GW, Taylor DO,
Higgins R, Platt L, and CTRD
J Heart and Lung Transplant 2001; 20:185.

3. Background
• Despite several improvements no effective therapy has been
developed.
• Prognosis is still poor.
• Many group stated the unsuitability of these patients for heart
re-transplantation because early re-transplantation within 6
months of primary HT is associated with poorer survival.
• There is now a growing consensus that early mechanically
bridge to recovery may result in better survival

4. Background
• Few changes have been done in heart
preservation.
• New techniques of myocardial storage are under
evaluation to reduce the incidence of EGF and
ameliorate the outcomes of Heart
Transplantation.
Two-decade analysis of cardiac storage for
transplantation
Stoica SC, Satchithananda DK, Dunning J, Large SR
Eur J Cardiothorac Surg 2001; 20: 792-98.

5. Background
• And help in discriminate good organs from unsuitable
organs, thus further reducing the hazard of EGF.

6. Background
• Incidence and Outcome is relatively unchanged during
last 10 years, also if donor age and quality is changed
and shifted to higher percentage of marginal donors
HEART TRANSPLANTS: CAUSE OF DEATH
0-30 Days
Donor Age by Year of Transplant
ADULT HEART TRANSPLANT RECIPIENTS: (N = 3,771)
Cause of Death (Deaths: January 1992 - June 2009) Cardiac Allograft
63 (1.7%)
Vasculopathy
Acute Rejection 242 (6.4%)
Lymphoma 2 (0.1%)
Malignancy, Other 4 (0.1%)
CMV 4 (0.1%)
Infection, Non-CMV 484 (12.8%)
Graft Failure 1,553 (41.2%)
Technical 270 (7.2%)
ISHLT Other 201 (5.3%)
2010
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141 Multiple Organ Failure 508 (13.5%)
Renal Failure 24 (0.6%)
ISHLT 2010 Pulmonary 154 (4.1%)
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141 Cerebrovascular 262 (6.9%)

7. Aim of the Study
• Identify, in a single centre experience, the risk factors
associated with EGF after heart transplantation and their
interaction, and describe course and prognosis of EGF.
• Early Graft Failure (EGF) was defined as a mono-
ventricular or biventricular Low Output Syndrome (LOS)
with a cardiac index <2L/min/m2, higher filling pressures
(RAP or PCP>20mmHg) in the first 24 hours with the
need of high inotropic support, systemic and/or
pulmonary vasodilators, IABP, prolonged intubation with
high O2 concentrations

8. Methods
Single Centre Retrospective Analysis on a consecutive series of
Transplants done between January 2000 and December 2008:
• 317 heart transplantation in 312 patients (5 retransplant).
• All grafts were preserved with the same solution (Celsior®)
• All transplants with the Shumway technique.
• Data of all patients transplanted are prospectively entered in a
dedicated database containing all preoperative data of recipients.
• More than 100 variables were entered for every patient.

9. Statistical Method
• Bivariate analysis to identify significant factors associated with EGF
without the propensity score correction.
• Hierarchical cluster analysis of pre-operative recipient/donor clinical
profile and procedure of matching.
• Single step discriminant analysis to create a propensity score for the
likelihood to develop EGF.
• Propensity score was divided in tertiles of risk resulting in 3 separate
groups of patients.
• First two groups (low and moderate risk) were pooled because
clinically homogeneous.
• Bivariate analysis was performed between first 2 tertiles vs the third,
thus including the propensity score derivates groups of patients.

10. Results
• 32 patients (10,1%) experienced Low Output Syndrome (LOS) for
Early Graft Failure
• 10 patients (3,1%) Right Ventricular Failure (5 deaths).
• 22 (6,9%) Biventricular failure (13 deaths).
• EGF mortality was 52,9% (18 pts).
• One patient (21 year old) experiencing EGF was re-transplanted
after less than 24 hour of ECMO and died for EGF.
• Incidence of MOF was respectively 50% in RVF and 31% in BEGF.

11. Results / Recipient Characteristics
Baseline and Surgical Characteristics Overall No EGF EGF P
(n=317) (n=285) (n=32)
Recipient Age(years) 47.2±14 47.4±14 46.1±13 0.3
Recipient PVRI 3.9±2.5 3.9±2.5 4.0±2.1 0.86
Recipient Sex (%) 0.01
Male 79.8 87.7 12.3
Female 20.2 98.4 1.6
Etiology 0.7
Idiopatic 36.6 91.4 8.6
Ischemic 40.4 87.5 12.5
Valvular 6.6 90.5 9.5
Other 16.4 92.3 7.7
Non-Idiopatic 63.4 89.1 10.9
Redo Surgery 20.8 <0.001
Yes 77.3 22.7
No 93.2 6,8
Diabetes mellitus (type I or II) (%) 18.6 0.62
Yes 88.1 11.9
No 90.3 9.7
Preoperative Hgb 13±2.1 13±2.0 12.4±2.4 0.055
UNOS Status(%) 0.08
1 14.8 83.0 17
2a 12.3 84.6 15.4
2b 72.9 92.2 7.8
Hospitalized(%) 27.1 0.03
Yes 83.7 16.3
No 92.2 7.8
Baseline eGFR (ml/min/1.73m2 ) 78.4±34 78.8±33 75.0±35 0.55

12. Results
Match and Operative Characteristics
Baseline and Surgical Characteristics Overall No EGF EGF P
(n=317) (n=285) (n=32)
Donor Age 32.3±12 32.1±12 34.5±11 0.30
Donor Sex 0.87
Male 65.2 91 9
Female 34.8 91.5 8.5
Weight D/R mismatch (>20%) 12.9 0.03
Yes 82.1 17.9
No 92.4 7.6
Donor High Inotrope 31.6 0.03
Yes 86.2 13.8
No 93.6 6.4
RBC Transfused Units 2.8±4.4 2.4±3.5 5.9±8.6 <0.001
Induction Drug Low Dosage (1-1.5mg/kg/die) 0.03
ATG Fresenius 48.6 86.9 13.1
Thymoglobuline 51.4 93.8 6.2
Troponine 10.4±8.4 9.7±6.0 16.0±18.6 <0.001
Total Ischemic Time 180±43 179±43 195±36 0.04

14. Results (Propensity Included)
Incidence of Oucomes and Relative Risks
in Study Population Stratified for Propensity Score
25% RR 7,15
RR 3,8
RR 3,64 RR 2,18
RR 1,81 RR 1,1
20%
15%
10%
5%
0%
EGF (%) Hospital Mortality Actual 1-year AKI (ΔGFR> 50%) MOF 1-year Infection
(%) Mortality (%)
Low / Intermediate Risk (n=211) Outcomes
High-Risk (n=106)

15. Results
Propensity Score Risk Group
Low / Intermediate Risk High-Risk p
Baseline and Surgical Characteristics (n=211) (n=106)
Recipient Age(years) 48.1±13 45.3±15 0.09
Recipient PVRI 3.8±2.4 4.2±2.6 0.13
Recipient Sex (%) <0.001
Male 73.0 93.4
Female 27.0 6.6
Etiology 0.03
Idiopatic 40.3 29.2
Ischemic 40.3 40.6
Valvular 2.4 15.1
Other 17.1 15.1
Non-Idiopatic 59.7 70.8
Redo Surgery 4.7 52.8 <0.001
Diabetes mellitus (type I or II) (%) 18.5 18.9 0.93
Preoperative Hgb 13.2±2.0 12.7±2.2 0.054
UNOS Status(%) <0.001
1 9.5 25.5
2a 10 17.0
2b 80.6 57.5
Hospitalized(%) 19.4 42.5 <0.001
Baseline eGFR (ml/min/1.73m2 ) 80.8±34 73.5±32 0.07

16. Results
Propensity Score Risk Group
Low / Intermediate Risk High-Risk p
Baseline and Surgical Characteristics (n=211) (n=106)
Donor Age 31.4±1,3 34.2±1,2 0.05
Donor Sex 0.52
Male 65.4 65.0
Female 34.6 35
Weight D/R mismatch (>20%) 5.9 27.6 <0.001
Donor High Inotrope 22.9 50 <0.001
RBC Transfused Units 2.0±2.9 4.2±5.1 <0.001
Induction Drug Low Dosage (1-1.5mg/kg/die) <0.001
ATG Fresenius 37.4 71.2
Thymoglobuline 62.6 28.8
Troponine 8.4±3.2 14.3±12.9 <0.001
Total Ischemic Time 171±42 197±40 <0.001

17. Results (Propensity Included)
Prevalence of Donor and Recipient Features
in Groups Stratified for Propensity Score
100%
RR 1,27
90%
RR 0,72
80%
RR 1,18 RR 1,92
70% RR 1
60%
RR 10,6 RR 2,17
50% RR 1,03 RR 2,26
RR 0,72
40%
30% RR 2,6 RR 4,67
RR 1 RR 1,7
20%
10%
0%
1
2a
2b
ry
s
or
tic
e
e
ti c
t
e
ic
ch
en
iu
liz
et
p
S
ge
on
m
a
a
en
at
tro
S
S
NO
b
i
ta
op
op
e
ip
r
NO
NO
D
ia
ism
Su
ch
es
pi
ec
o
i
i
D
U
Id
e
-Id
In
os
Is
Fr
U
U
al
R
m
o
h
H
on
ed
M
e
G
ig
R
al
N
R
AT
rH
D/
M
t
o
gh
on
ei
D
W
Low / Intermediate Risk (n=211) High-Risk (n=106) RR: Relative Risk for EGF

18. Conclusions
• Male sex Recipients •Higher Donor Age •ATG Formulation
• Non idiopatic •High Donor Support •RBC units
• Redo •D/R Weight Mismatch •Troponine Release
• Hospitalized •Ischemic Time
• UNOS status 1
Were proved determinants for high likelihood for EGF
• Since such characteristics are not readily modifiable,
optimization of donor/recipient matching is crucial to reduce the
risk of EGF.
• Surgical haemostasis during reopening or during implantation
should be as meticulous as possible even in the constraint of
higher ischemic time to reduce RBC consumption.

19. Purposes
• As for urgent recipients, changes in allocation rules
should be considered in recipients with rare groups,
immunized or obese, thus looking at the general
interest.
• Changes in strategies of myocardial protection for
marginal donors with long ischemic time (Long Redo
Operations, Long Projected ischemic time for
urgency recipients) should be evaluated to better
protect allograft function, discard unsuitable organs
and work without the ischemic time pressure to
reduce blood losses.