Outcome of Extracorporeal MembraneOxygenation for Early Primary GraftFailure After Pediatric Heart Transplantation
Cecile Tissot, MD, Shannon Buckvold, MD, Christina M. Phelps, MD, D. Dunbar Ivy, MD,David N. Campbell, MD, Max B. Mitchell, MD, Suzanne Osorio da Cruz, DVM,Bill A. Pietra, MD, Shelley D. Miyamoto, MD
Aurora, Colorado
Objectives We sought to analyze the indications and outcome of extracorporeal membrane oxygenation (ECMO) for earlyprimary graft failure and determine its impact on long-term graft function and rejection risk.
Background Early post-operative graft failure requiring ECMO can complicate heart transplantation.
Methods A retrospective review of all children requiring ECMO in the early period after transplantation from 1990 to 2007was undertaken.
Results Twenty-eight (9%) of 310 children who underwent transplantation for cardiomyopathy (n � 5) or congenitalheart disease (n � 23) required ECMO support. The total ischemic time was significantly longer for ECMO-rescued recipients compared with our overall transplantation population (276 � 86 min vs. 242 � 70 min, p �
0.01). The indication for transplantation, for ECMO support, and the timing of cannulation had no impact on sur-vival. Hyperacute rejection was uncommon. Fifteen children were successfully weaned off ECMO and dischargedalive (54%). Mean duration of ECMO was 2.8 days for survivors (median 3 days) compared with 4.8 days for non-survivors (median 5 days). There was 100% 3-year survival in the ECMO survivor group, with 13 patients (46%)currently alive at a mean follow-up of 8.1 � 3.8 years. The graft function was preserved (shortening fraction 36� 7%), despite an increased number of early rejection episodes (1.7 � 1.6 vs. 0.7 � 1.3, overall transplant pop-ulation, p � 0.05) and hemodynamically comprising rejection episodes (1.3 � 1.9 vs. 0.7 � 1.3, overall trans-plant population, p � 0.05).
ublished by Elsevier Inc. doi:10.1016/j.jacc.2009.04.062
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eart transplantation in children with end-stage heartailure secondary to cardiomyopathy or failed palliation ofongenital heart disease (CHD) is a good option withmproving outcomes (1). One of the most common com-lications in the immediate period after transplantation isarly graft failure. Graft failure can result from long isch-mic time, inadequate myocardial preservation at time ofrocurement, hyperacute rejection, or poor adaptation ofhe graft to the recipient’s hemodynamic environment (2).ither as a consequence of left heart failure or as a result of
rom the Children’s Hospital of Denver, Aurora, Colorado. Dr. Ivy is a consultant forctelion, United Therapeutics, and Gilead.
oManuscript received February 24, 2009; revised manuscript received April 13,
009, accepted April 20, 2009.
PVR) in many pediatric recipients is increased, resulting inhe risk of right ventricular failure after transplantation.
See page 738
easures aimed at decreasing PVR after transplantationnclude the use of inhaled nitric oxide as well as medicationsith pulmonary vasodilator effects, such as prostacyclin,
soproterenol, and milrinone (3). Graft ventricular functions also commonly supported post-operatively with inotropese.g., dopamine, dobutamine, low-dose epinephrine, orilrinone). However, despite these interventions, ventricu-
ar failure may persist, and mechanical circulatory supportecomes necessary. Extracorporeal membrane oxygenationECMO) is widely used for post-cardiotomy low cardiac
utput syndrome (LCOS) in children and is occasionally
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731JACC Vol. 54, No. 8, 2009 Tissot et al.August 18, 2009:730–7 ECMO for Primary Graft Failure in Children
equired after pediatric heart transplantation (4–6). Thebjectives of this study were as follows: 1) to describe thendications and outcome of ECMO for early primary graftailure after heart transplantation in children; 2) to identifyarkers predictive of ECMO survival in this patient pop-
lation; and 3) to determine the impact of early ECMO onong-term graft function and rejection risk.
ethods
ransplantation. We reviewed our institutional heartransplant database from 1990 to 2007. After approval byur institutional review board, all children requiringCMO in the post-operative transplantation period were
ncluded in the study. The course after transplantation forll eligible patients was reviewed. Our institutional trans-lantation methodology has been previously described butill be reviewed here (7). Donor hearts are procured in
tandard fashion, with great vessel lengths harvested asetermined by recipient anatomy. Roe’s solution is used foronor cardioplegia. One of the ECMO-rescued recipientsho survived underwent transplantation from a nonbeatingeart donor. Organ procurement in the setting of donationfter cardiac death has been previously described by ourroup (8). All of the other patients underwent transplanta-ion from standard brain-dead, heart-beating donors.
oreover, there were no changes in our procurementractices throughout the duration of this study period.Milrinone, dopamine, isoproterenol, and occasionally
pinephrine are commonly used for inotropic support in themmediate post-transplantation period. Nitric oxide is sys-ematically used in patients with an elevated PVR docu-ented before transplantation (PVR �5 Wood units/m2).riple immunosuppression with methylprednisolone for8 h, low-dose cyclosporine, and azathioprine is usederioperatively. Induction therapy with methylprednisolonend antithymocite globulin (Thymoglobulin, Genzymeorp., Cambridge, Massachusetts) was used until 1998, athich time Thymoglobulin was replaced by antithymocytelobulin (American Medical Resources, Nashville, Tennes-ee). Low-dose cyclosporine (target level 40 to 70 ng/ml)nd azathioprine were administered throughout induction.t discharge, maintenance immunosuppression consisted of
yclosporine (target level 175 to 225 ng/ml) and mycophe-olate mofetil (target level 2 to 4 �g/ml) (9). In patientsith an open chest or dependent on mechanical support
ECMO), induction therapy was withheld until chest clo-ure and/or decannulation was achieved because of thencreased risk of infection.
CMO. A standardized ECMO circuit was used withppropriately sized cannulas according to the patient size6). No other types of mechanical support devices were useduring the course of this study. Transthoracic cannulationhrough an open chest was used in all patients via the righttrium and ascending aorta. Pump flow was regulated
ccording to systemic perfusion, blood pressure tracing, and d
ystemic and mixed venous oxy-enation. Inotropic and ventila-ory supports were weaned asolerated during ECMO sup-ort. In patients with poor leftentricular function, venting ofhe left atrium or transcathetertrial balloon septostomy waserformed for left-sided decom-ression whenever required. Lefttrial decompression was indi-ated in the setting of inadequateeft ventricular decompression,esulting in increased left atrialressure and/or pulmonary edema.ctivated clotting time was main-
ained between 180 and 220 s witheparin infusion. Hemofiltration was used as required depend-
ng on the renal function and fluid status. Graft functionecovery was regularly assessed by transthoracic echocardiog-aphy. Increased inotropic and ventilatory support was used foreaning off ECMO. Chest closure was usually delayed until4 to 48 h after decannulation.utcome measures. Diagnosis of acute graft rejection in
ur institution is based on clinical presentation, echocardio-raphic or electrocardiographic findings, hemodynamics atime of catheterization, and/or endomyocardial biopsy evi-ence of rejection (10–12). Hemodynamically significant orompromising rejection is defined as a rejection episode forhich the patient required intravenous inotropic supporthile undergoing treatment for rejection. Hyperacute graft
ejection is defined as occurring during the immediateost-operative course after transplantation. Early rejection isefined as an acute graft rejection episode occurring duringhe first year after transplantation, and very early rejections occurring during the first month after transplantation.reatment of acute graft rejection includes anti–T-cell
ntibodies (antithymocyte globulin or OKT3) for 7 to 10ays in combination with steroids (4 doses) and thedministration of intravenous immunoglobulin per insti-utional protocol (12). Transplant coronary artery diseases diagnosed by angiography or intravascular ultrasoundnd is defined as any luminal irregularities or stenosis thataried from the patient’s previous angiography or intimalhickening �3 mm according to the Stanford classifica-ion (13,14).
Outcome was analyzed in 2 groups: 1) those successfullyeaned off of ECMO and discharged alive (survivor group);ersus 2) those who died while on ECMO or in theost-decannulation period (nonsurvivor group). The long-erm outcome of the ECMO survivors was compared withur overall transplant population.tatistical analysis. Data are presented as mean � SD.hen the population does not follow a normal distribution,edian values are given. Intergroup comparison was con-
Abbreviationsand Acronyms
ACT � activated clottingtime
CHD � congenital heartdisease
ECMO � extracorporealmembrane oxygenation
LCOS � low cardiac outputsyndrome
OHT � orthotopic hearttransplantation
PVR � pulmonary vascularresistance
VAD � ventricular assistdevice
ucted with an unpaired Student
t test. Comparison of
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732 Tissot et al. JACC Vol. 54, No. 8, 2009ECMO for Primary Graft Failure in Children August 18, 2009:730–7
roportion was made with the Fisher exact test. A p value0.05 was considered statistically significant. Statistical
nalysis was performed by use of the GraphPad Prismoftware (GraphPad Software Inc., La Jolla, California).raphs are represented with mean and SDs.
esults
ransplant demographics. From 1990 to 2007, 310 chil-ren underwent heart transplantation at our institution, and8 children who underwent transplantation (9%) werelaced on ECMO for post-operative primary graft failure.hese 28 children underwent transplantation for cardiomy-pathy (n � 5) or complex CHD (n � 23) and requiredCMO support for LCOS within 48 h of their transplan-
ation. The cardiomyopathy group included 4 patients withilated cardiomyopathy and one with restrictive cardiomy-pathy. The CHD group comprised 19 infants with hypo-lastic left heart syndrome variant and 4 children with otherorms of complex CHD. Six of the CHD patients hadrevious failed corrective or palliative heart surgery, whereas7 were referred for transplantation as the primary thera-eutic option. Patients’ ages ranged between 1 week and9.5 years (mean 1.3 � 3.7 years, median 0.3 years).wenty-four (86%) patients were infants (�1 year) at the
ime of transplantation. Weight ranged from 3 to 70 kgmean 7.8 � 12.5 kg, median 4.5 kg). This population didot follow a normal distribution because of a preponderancef infant recipients.ndications for ECMO. Three of the 28 patients were onCMO for cardiac failure before transplantation (1 survi-or, 33%). Extracorporeal membrane oxygenation wastarted in the operating room because of the inability toean from cardiopulmonary bypass in 16 patients (8 survi-ors, 50%), whereas the remaining 12 required ECMO inhe first 48 h after transplantation (7 survivors, 58%) andere cannulated in the cardiac intensive care unit. Fouratients had cardiac arrest before ECMO cannulation (4urvivors, 100%) and of those, 3 developed subsequenteurological deficits.ECMO was required for right ventricular failure in 9
atients (5 survivors, 56%) and for biventricular failure in 157 survivors, 47%). In the remaining 4 patients, the type ofentricular failure could not be clearly determined fromeview of the records. Only 1 patient was diagnosed withyperacute rejection as the cause of primary graft failure.his patient’s graft function did not improve with standard
ejection treatment, and the patient subsequently died fromemorrhagic complications 7 days after initiation of ECMOupport. One survivor required 4 days of ECMO support,rom which he was successfully weaned, but then heeveloped hemodynamically significant rejection at 6 daysfter transplantation and required inotropic support. Thisatient had complete recovery of graft function after treat-ent of this rejection episode and was eventually discharged
ome. f
utcome of ECMO. When comparing the survivor groupith the nonsurvivor group, we found no significant differ-
nce in the time on the waiting list, age at transplantation,eight of the recipient, donor/recipient weight ratio, total
schemic time, sex, or blood type distribution between the 2roups (Table 1). The proportion of infants �1 year of ageas not significantly different between the 2 groups (87% of
urvivors were infants vs. 85% of nonsurvivors, p � 0.64).here was no statistical difference in the survival rate for the
ardiomyopathy group (2 of 5, 40%) compared with theHD group (13 of 23, 56%, p � 0.42). Among the CHD
roup, the survival rate was also not statistically different fornfants with hypoplastic left heart syndrome (11 of 19, 58%)ompared with patients with other congenital heart defects2 of 5, 40%, p � 0.41).
There was no significant difference in the proportion ofatients with previous heart surgery and sternotomy beforeransplantation between the survivors (n � 3, 20%) and theonsurvivors (n � 3, 23%, p � 0.6). The donors’ ejectionraction was significantly lower in the survivor group (65 �%, survivors vs. 71 � 3%, nonsurvivors, p � 0.004), andlthough the difference in shortening fraction did not reach
statistically significant level, there was a trend towardower shortening fraction in the survivor group (32 � 5%,urvivors vs. 41 � 4%, nonsurvivors, p � 0.08). There wastrend toward greater peak creatinine (1.3 � 0.7 mmol/l,
urvivors vs. 1.7 � 1 mmol/l, nonsurvivors, p � 0.1) andactate (10.1 � 4.5 mmol/l, survivors vs. 13.4 � 5.7
mol/l, nonsurvivors, p � 0.19) while on ECMO in theonsurvivor group, but these levels did not reach statis-ical significance.
Fifteen children were successfully weaned off of ECMOnd discharged (54%), whereas 13 patients died (46%) ofersistent heart failure (n � 9), diffuse bleeding (n � 3),nd/or sepsis (n � 4) at a mean time of 9 days (median 7ays) after transplantation. Among the deceased patients, 7ere unable to be decannulated and died at a mean time ofdays (median 6 days) from the initiation of ECMO
upport. Six patients were decannulated and died at a meanime of 14 days (median 10 days) from the initiation ofCMO support and 10 days (median 6 days) after ECMOecannulation. The cause of death in this subset of patientsas mostly related to persistent cardiac failure with end-rgan dysfunction and subsequent cardiac arrest. One pa-ient was decannulated after 4 days, experienced persistenteart failure and multiorgan dysfunction (hepatic and renalailure with the need for dialysis), and could not beesuscitated after cardiac arrest that occurred 37 days afterransplantation. Mean duration of ECMO was 2.8 days forurvivors (median 3 days) versus 4.7 days (median 5 days)or nonsurvivors (p � 0.01), with all survivors having beenn ECMO no longer than 4 days (Fig. 1). Mean durationf ECMO in nonsurvivors weaned off of ECMO was 4 daysmedian 4.5 days) compared with 5.3 days (median 7 days)
or the nonsurvivors unable to be decannulated (p � 0.05).
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733JACC Vol. 54, No. 8, 2009 Tissot et al.August 18, 2009:730–7 ECMO for Primary Graft Failure in Children
haracteristics of ECMO-rescued recipients. Whenomparing the recipients requiring ECMO support for earlyost-operative graft failure (survivors and nonsurvivorsombined) with our overall transplant population, we foundhat there was a significant difference with a longer totalschemic time (276 � 86 min vs. 242 � 70 min, p � 0.008)Fig. 2), a younger age (1.3 � 3.7 years vs. 4.8 � 6.4 years,� 0.002), and a smaller weight at transplantation (7.8 �
2.6 kg vs. 16.8 � 18.4 kg, p � 0.0001) for the ECMO-escued patients (Table 2). Indications for transplantation
ata of Surviving Versus Nonsurviving Pediatric Heart Transplantecipients Rescued With ECMO Support for Early Post-Operative GTable 1 Data of Surviving Versus Nonsurviving Pediatric HeartRecipients Rescued With ECMO Support for Early Post
cardiomyopathy vs. congenital heart disease, p � 0.1), the b
aiting time on the list (81 � 107 days vs. 77 � 97 days,� 0.4), and the donor/recipient weight ratio (1.9 � 1 kg
s. 1.8 � 0.6 kg, p � 0.38) were not different between thesegroups of patients.ong-term outcome. Neurological complications were
ound in 4 of the 15 (27%) survivors, 2 patients remainingith permanent neurological impairment and 2 with tran-
ient and resolved seizures. All of the patients with neuro-ogical disability were emergently cannulated in the cardiacntensive care unit, and 3 of these patients had cardiac arrest
ailureplantrative Graft Failure
Nonsurvivors of ECMO (n � 13)
n % Mean � SD Median % p Value
1 10.3 � 2.5 5.4 0.17
5 9.8 � 4.4 10.9 0.29
1.9 � 1 1.8 0.49
2 2 � 5.2 0.3 0.19
11 85% 0.64
5 38% 0.47
8 62% 0.47
5 38.5% 0.5
5 38.5% 0.5
3 23% 0.5
0 0% 0.5
3 23% 0.42
10 77% 0.42
8 62% 0.42
3 23% 0.6
72 � 59 59 0.3
279 � 89 275 0.36
71 � 3 70 0.004
41 � 4 40 0.08
2 15% 0.44
4 31% 0.59
8 62% 0.59
1 7% 0.59
0 0% 0.06
8 62% 0.48
5 38% 0.48
2 1.7 � 1 1.6 0.1
2 13.4 � 5.7 11.8 0.19
4.7 � 2.6 5 0.006
% 6 46% 0.001
0 0% —
0 0% —
left heart syndrome; OHT � orthotopic heart transplantation.
raft FTrans-Ope
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69
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62
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efore cannulation. Overall, there was 100% 3-year survival
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734 Tissot et al. JACC Vol. 54, No. 8, 2009ECMO for Primary Graft Failure in Children August 18, 2009:730–7
or the patients successfully weaned off of ECMO andischarged. Two of the survivors died at 4.3 and 7.8 yearsfter transplantation, respectively: 1 from chronic rejectionnd graft failure and the other from transplant coronaryrtery disease. Thirteen patients (46%) are still currentlylive at a mean follow-up of 8.1 � 3.8 years; 3 are �10 yearsnd 10 are �5 years after transplantation.
The graft function in surviving patients is normal, with aean shortening fraction by echocardiography of 36 � 7%
nd no patient with a shortening fraction �25%. The meanjection fraction obtained by cardiac catheterization was5 � 10% and the cardiac index by thermodilution was.5 � 1.3 l/min/m2. The mean number of very early graftejection episodes was not different for the ECMO-rescuedatients compared with our overall transplant population0.6 � 0.6 vs. 0.4 � 0.6, p � 0.1). The ECMO survivorsad an increased number of early rejection episodes (1.7 �.6 vs. 1.0 � 1.4, p � 0.03) and an increased number ofemodynamically compromising rejections (1.3 � 1.9 vs..7 � 1.3, p � 0.04) compared with the overall transplantopulation (Table 3, Fig. 3). However, there was noifference in the mean overall number of acute cellularejection episodes between the survivors and the overallransplant population (2.9 � 3 vs. 2.1 � 2.7, respectively, p
0.18). The incidence of transplant coronary artery diseaseas not increased in the ECMO survivors (2 of 15, 13%
ompared with 16% in our overall transplant population,� NS).
iscussion
arly primary graft failure after heart transplantation inhildren is associated with significant rates of mortality andorbidity. Extracorporeal membrane oxygenation is widely
sed and is well established to support circulatory functionn children with post-cardiotomy LCOS (4,15). On theasis of this experience, ECMO has become a reasonable
Figure 1 Duration of Support for ECMOSurvivors Versus Nonsurvivors
The extracorporeal membrane oxygenation (ECMO) duration for primarygraft failure between ECMO survivors versus nonsurvivors (p � 0.01) is shown.
ption for early graft failure in children after cardiac
ransplantation (4,6,16 –19). Ventricular assist devicesVADs) are better suited for patients expected to requireong-term support; therefore, ECMO remains the mostommonly used method of mechanical circulatory supportfter cardiac surgery or in the post-transplantation period ofediatric patients. This article describes the early and lateutcome of ECMO support for early cardiac graft failure inhildren and represents the largest pediatric experience toate.In our study, primary post-operative graft failure neces-
itating ECMO was not uncommon (9%). The majority ofatients supported with ECMO in this study were infantecipients (86% �1 year of age), reflecting the usual distri-ution of pediatric heart transplantation recipients, with theajority of heart transplantations occurring in the �1-year-
ld group (1). Nevertheless, pediatric heart recipients re-uiring ECMO support for early graft failure were signifi-antly younger (p � 0.01) and had a lower weight atransplantation (p � 0.001) compared with our overallransplantation population. Moreover, their total ischemicime was significantly longer (p � 0.01), indicating thatarvesting technique and time are crucial and that a longer
schemic time is a major risk factor for graft dysfunction.The indication for ECMO cannulation did not influence
he outcome, and the survival rate was not different inatients presenting with biventricular compared with iso-
ated right ventricular failure. In addition, the survival rateas not significantly different for patients with cardiomy-pathy compared with patients with CHD. Poor donorraft function has been implicated as a cause of graftysfunction after transplantation, but this was not consid-red different in our study, with no difference in thehortening fraction obtained by M-mode echocardiography
All Tx ECMO rescued0
100
200
300
400p<0.01
276±89
242±70
min
ute
s
Figure 2 Total Ischemic Time of ECMO-RescuedVersus All Transplant Recipients
Total ischemic time between extracorporeal membrane oxygenation (ECMO)-rescued recipients compared with our overall transplant population (p � 0.01)is shown. Tx � transplants.
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735JACC Vol. 54, No. 8, 2009 Tissot et al.August 18, 2009:730–7 ECMO for Primary Graft Failure in Children
etween ECMO survivors and nonsurvivors. Although thejection fraction, considered less accurate compared withhe shortening fraction when obtained by M-mode echo-ardiography, was statistically lower in the survivor group,he mean and median values remain within the normalimit, rendering this difference difficult to interpret.
The timing of ECMO cannulation was also not predic-ive of outcome. Survival was not significantly differentetween patients started on ECMO in the operating roomor failure to wean from cardiopulmonary bypass comparedith those cannulated in the first 48 h after transplantation
or hemodynamic instability or cardiac arrest in the cardiacntensive care unit. This is in contradiction to the previouseport by Galantowicz and Stolar (19), who reported nohance of survival if the fresh cardiac allograft could notupport the patient after cardiopulmonary bypass. More-ver, cardiac arrest before ECMO cannulation was not aegative predictive factor for survival in our series, and allatients who had cardiac arrest survived.This result clearly differs from survival rates of 33% to
3% for those patients who experience cardiac arrest andhen are placed on ECMO as a bridge to transplantation18,20 –23). This finding suggests that the donor’s hearts more likely to recover after cardiac arrest and subse-uent ECMO support than the failing ventricle of a
erioperative Data of Pediatric Heart Transplant Recipients Rescued Wor Early Post-Operative Graft Failure Compared With the OverallTable 2 Perioperative Data of Pediatric Heart Transplant Recipiefor Early Post-Operative Graft Failure Compared With
ECMO-Rescued Recipients(n � 28)
Data Mean � SD Med
Demographics
Recipient weight (kg) 7.8 � 12.6
Donor/recipient weight ratio 1.9 � 1
Age at OHT (yrs) 1.3 � 3.7
Total ischemic time (min) 276 � 89 27
Waiting time (days) 81 � 107 6
Indication for transplantation
Cardiomyopathy 5 1
CHD 23 8
ignificant values (p � 0.05) are indicated in bold.CHD � congenital heart disease; other abbreviations as in Table 1.
Outcome Data of Survivors Rescued With ECMOPost-Operative Graft Failure Compared With theTable 3 Outcome Data of Survivors RescuedPost-Operative Graft Failure Compa
DataSurviv
(
Outcome
TCAD
Rejections
Total 2
Very early (within 30 days of transplantation) 0
Early (within 1 year of transplantation) 1
Hemodynamic compromising 1
Values are n (%) or mean � SD. Significant values (p � 0.05) are indicated iTCAD � transplant coronary artery disease; other abbreviations as in Table
atient who is in need of transplantation. Importantly,owever, emergent cannulation was associated with areater risk of neurologic complications, and all survivorsith neurological sequelae were either cannulated emer-ently or experienced cardiac arrest before cannulation.herefore, anticipating graft failure with elective cannu-
ation before hemodynamic collapse is likely to improveeurologic outcome.The mean duration of ECMO support in survivors was
ignificantly less than nonsurvivors, and all survivors wereecannulated within 4 days of initiation of support. Thisnding confirms what has been previously reported in the
nfant population by our institution (6). In the Mitchellt al. (6) infant study, ECMO support for �4 days wasssociated with death and increased risk of morbidity,articularly sepsis, bleeding, and neurologic sequelae. Re-overy of ventricular function within 8 days of ECMOupport has been reported and may become more commons ECMO and other mechanical support technologyrogress and improve over time.However, on the basis of our institutional experience
escribed here, consideration could be given to listing foretransplantation or transition to a VAD if the patient is notecannulated within 4 days of initiation of ECMO support6,18,22). Of course, the clinical situation for each individ-
ECMO Supportsplant Populationescued With ECMO SupportOverall Transplant Population
Overall Transplant Population(n � 310)
Mean � SD Median % p Value
16.8 � 18.4 7.2 0.0001
1.8 � 0.6 1.7 0.38
4.8 � 6.4 0.96 0.002
242 � 70 247.5 0.008
77 � 97 50 0.4
96 31% 0.1
214 69% 0.1
port forall Transplant Populationh ECMO Support forith the Overall Transplant Population
ECMO5)
Overall TransplantPopulation(n � 310) p Value
) 52 (16) 0.54
2.1 � 2.7 0.13
.6 0.4 � 0.6 0.10
.6 1.0 � 1.4 0.03
.9 0.7 � 1.3 0.04
ithTrannts Rthe
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SupOverWitred W
ors ofn � 1
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736 Tissot et al. JACC Vol. 54, No. 8, 2009ECMO for Primary Graft Failure in Children August 18, 2009:730–7
al patient must be carefully considered when making theecision to relist for transplantation. The already presenthallenges of shortage of donor supply and increased risk ofransplantation after support with mechanical assistanceequire that the decision to list for retransplantation shoulde reserved for those patients deemed to be good candidatesor this option. Those individuals requiring ECMO afterransplantation who have evidence of severe neurologicnjury, irreversible organ injury, hyperacute rejection, andnfection would not be appropriate candidates for retrans-lantation. The only other factor that correlated withurvival was a lower donor ejection fraction. This findinguggests that the use of marginal donors, especially for thenfant population where donor shortage is a problem, mayot compromise outcome even if ECMO rescue is necessary
n the early post-transplantation period (24).Overall, 54% of the patients supported with ECMO were
uccessfully weaned and discharged alive, which is compa-able to what has been previously reported in the pediatricopulation (6,16,17). Long-term survival of those survivingo hospital discharge was excellent, with 100% alive at 3ears after transplantation.
Although the number of early (within the first year afterransplantation) acute graft rejection episodes was signifi-antly increased in the ECMO survivors compared with ourther transplant recipients, there was no difference in theotal number of acute graft rejection episodes between theseroups. The number of hemodynamic compromising rejec-ions per patient also was significantly increased in theCMO survivors (1.3 � 1.9 vs. 0.7 � 1.2 in the overall
ransplant population, p � 0.05). In fact, 20% of the
Figure 3 Rejection Episodes for ECMOSurvivors Versus All Transplants
Rejection episodes comparing extracorporeal membrane oxygenation (ECMO)survivors with all patients transplanted in our program are shown. Early rejec-tions are defined as rejection episodes during the first year after transplanta-tion, and very early rejection episodes are defined as occurring during the firstmonth after transplantation. Hemodynamic compromising rejections aredefined as abnormal hemodynamics documented at catheterization comparedwith the patient’s previous baseline and dependence on inotropic support. hemcompr � hemodynamic compromise.
CMO survivors presented with at least 1 episode ofG
The incidence of transplant coronary artery disease in theCMO survivors (13%) was not increased compared withur overall transplantation population (16%). This finding isomewhat unexpected, because the increased frequency ofarly and hemodynamic compromising rejection in theCMO survivors are factors that have been associated with
he development of coronary vasculopathy (25,26). Thisnding is not related to timing of follow-up becauseransplant coronary vasculopathy in our program is diag-osed at a mean time of 6.4 years after transplantation, andhe mean follow-up of the ECMO survivors is 8.1 years.inally, despite increased frequency of early and severe acuteraft rejection in the survivors, the graft function at long-erm follow-up is normal.tudy limitations. This study is limited by its descriptiveature and the small sample of patients.
onclusions
rimary graft failure requiring mechanical circulatory sup-ort in the early period after transplantation is not uncom-on in children (9%), and a long ischemic time is a major
isk factor of graft dysfunction. Pediatric cardiac allograftsan be successfully salvaged by ECMO in a reasonableroportion of patients (54%). Although cardiac arrest beforeCMO as well as emergent cannulation did not impact
urvival, these were associated with adverse neurologicutcome. The duration of cannulation was important in oureries, with no child in this study surviving ECMO supportor �4 days. If clinical recovery seems unlikely and theatient is a good candidate for retransplantation, consider-tion to relist and/or transition to VAD support is reason-ble if �4 days of support is required. Importantly, long-erm outcome in those patients supported by ECMO forrimary graft failure and surviving to hospital discharge wasxcellent, with 100% 3-year survival and normal graftunction despite an increased number of early rejection andemodynamic compromising rejection episodes. Therefore,CMO as a bridge to graft recovery after transplantation
an be used without altering the long-term outcome of thishallenging group of high-risk post-operative patients.
cknowledgmentshe authors thank all of the transplant coordinators of thehildren’s Hospital Heart Institute for their hard work with
he patients and Sam Schofield for his help with theediatric heart transplant database.
eprint requests and correspondence: Dr. Cecile Tissot, Uni-ersity Children’s Hospital of Geneva, 6, rue Willy Donze, 1211
737JACC Vol. 54, No. 8, 2009 Tissot et al.August 18, 2009:730–7 ECMO for Primary Graft Failure in Children
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ey Words: extracorporeal membrane oxygenation y child y heartransplantation y right-sided heart failure y left-sided heart failure y
