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

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.

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.

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

Two-decade analysis of cardiac storage for transplantation

Stoica SC, Satchithananda DK, Dunning J, Large SR

Eur J Cardiothorac Surg 2001; 20: 792-98.

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.

Background

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

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

ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2009)

CAUSE OF DEATH0-30 Days

(N = 3,771)

Cardiac Allograft Vasculopathy

63 (1.7%)

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%)

Other 201 (5.3%)

Multiple Organ Failure 508 (13.5%)

Renal Failure 24 (0.6%)

Pulmonary 154 (4.1%)

Cerebrovascular 262 (6.9%)

2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

0%

10%

20%

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0-10 11-17 18-34 35-49 50-59 60+ Mean AgeM

ean

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ears

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HEART TRANSPLANTS:Donor Age by Year of Transplant

2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

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

Methods

Single Centre Retrospective Analysis on a consecutive series ofTransplants 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.

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.

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.

Results / Recipient CharacteristicsBaseline and Surgical Characteristics Overall

(n=317)No EGF(n=285)

EGF (n=32)

P

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 (%)MaleFemale

79.820.2

87.798.4

12.31.6

0.01

EtiologyIdiopaticIschemicValvularOther Non-Idiopatic

36.640.46.6

16.463.4

91.487.590.592.389.1

8.612.59.57.7

10.9

0.7

Redo SurgeryYesNo

20.877.393.2

22.76,8

<0.001

Diabetes mellitus (type I or II) (%)Yes No

18.688.190.3

11.99.7

0.62

Preoperative Hgb 13±2.1 13±2.0 12.4±2.4 0.055

UNOS Status(%) 12a2b

14.812.372.9

83.084.692.2

1715.47.8

0.08

Hospitalized(%)YesNo

27.183.792.2

16.37.8

0.03

Baseline eGFR (ml/min/1.73m2 ) 78.4±34 78.8±33 75.0±35 0.55

Results Match and Operative Characteristics

Baseline and Surgical Characteristics Overall(n=317)

No EGF(n=285)

EGF (n=32)

P

Donor Age 32.3±12 32.1±12 34.5±11 0.30

Donor SexMaleFemale

65.234.8

9191.5

98.5

0.87

Weight D/R mismatch (>20%)YesNo

12.982.192.4

17.97.6

0.03

Donor High InotropeYesNo

31.686.293.6

13.86.4

0.03

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)ATG FreseniusThymoglobuline

48.651.4

86.993.8

13.16.2

0.03

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

Results (Propensity Included)

RR 7,15

RR 3,64 RR 2,18RR 1,81

RR 3,8

RR 1,1

0%

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25%

EGF (%) Hospital Mortality(%)

Actual 1-yearMortality (%)

AKI (ΔGFR> 50%) MOF 1-year Infection

Outcomes

Incidence of Oucomes and Relative Risks in Study Population Stratified for Propensity Score

Low / Intermediate Risk (n=211)High-Risk (n=106)

Results Propensity Score Risk Group

Baseline and Surgical CharacteristicsLow / Intermediate Risk

(n=211)High-Risk (n=106)

p

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 (%)MaleFemale

73.027.0

93.46.6

<0.001

EtiologyIdiopaticIschemicValvularOther Non-Idiopatic

40.340.32.4

17.159.7

29.240.615.115.170.8

0.03

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(%) 12a2b

9.510

80.6

25.517.057.5

<0.001

Hospitalized(%) 19.4 42.5 <0.001

Baseline eGFR (ml/min/1.73m2 ) 80.8±34 73.5±32 0.07

Baseline and Surgical CharacteristicsLow / Intermediate Risk

(n=211)High-Risk (n=106)

p

Donor Age 31.4±1,3 34.2±1,2 0.05

Donor SexMaleFemale

65.434.6

65.035

0.52

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)ATG FreseniusThymoglobuline

37.462.6

71.228.8

<0.001

Troponine 8.4±3.2 14.3±12.9 <0.001

Total Ischemic Time 171±42 197±40 <0.001

Results Propensity Score Risk Group

Results (Propensity Included)

RR 1,27

RR 0,72RR 1,03

RR 1,18

RR 10,6

RR 1RR 2,6

RR 1,7

RR 0,72

RR 2,26

RR 1

RR 4,67

RR 2,17

RR 1,92

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Male

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Redo

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UNOS 2

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Male

Don

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High

Inot

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ATG F

rese

nius

Prevalence of Donor and Recipient Features in Groups Stratified for Propensity Score

Low / Intermediate Risk (n=211) High-Risk (n=106) RR: Relative Risk for EGF

Conclusions• Male sex Recipients• Non idiopatic• Redo• Hospitalized • 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.

•Higher Donor Age•High Donor Support •D/R Weight Mismatch

•ATG Formulation•RBC units •Troponine Release•Ischemic Time

• 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.

Purposes