does the pretransplant unos status modify the short- and long-term cardiac transplant prognosis?

Does the Pretransplant UNOS Status Modify theShort- and Long-Term Cardiac Transplant Prognosis?Olivier Baron, MD, Alexandre Le Guyader, MD, Jean Noel Trochu, MD,Marc Burban, MD, Jean Christophe Chevalier, MD, Michelle Treilhaud, MD,Thierry Petit, MD, Oussama Al Habash, MD, Philippe Despins, MD,Jean Luc Michaud, MD, and Daniel Duveau, MDUnite de Transplantation Thoracique, Service de Chirurgie Thoracique et Cardiovasculaire, Hopital G et R Laennec, Nantes,France

Background. We compared the morbidity and mortalityrates of patients who had urgent heart transplantation ortransplantation after bridging with a ventricular assistdevice, with the rates of patients whose clinical stabilityallowed them to wait at home.

Methods. From March 1985 to December 2000, 404patients underwent heart transplantation in a singlecenter. There were 273 patients with UNOS status 2 (US2), 103 patients with UNOS Status 1A (US 1A), and 28patients with UNOS Status 1B (US 1B). We compared thegroups retrospectively with respect to pretransplantationstatus and operative results.

Results. Despite more severely impaired hemodynam-ics and a significantly higher preoperative infection ratein US 1A and 1B patients, there were no statisticallysignificant differences in survival rates among the threegroups. Donor sex and age, cytomegalovirus and toxo-

plasmosis, mismatch rate, ischemic time, method of myo-cardial protection, and operative technique did not differstatistically among the three groups. Length of intensivecare unit stay, postoperative morbidity, first year postop-erative rejection rate, and graft occlusive vascular diseaserate were statistically similar among the three groups.Although pretransplantation cancer assessment was lesscomplete in US 1A and 1B than in US 2 patients, thelate-cancer rate was not statistically different among thethree groups.

Conclusions. These data suggest that urgently trans-planted patients have both early and long term morbidityand mortality similar to those of patients waiting fortransplantation at home or with a ventricular assistdevice.

(Ann Thorac Surg 2003;75:1878–85)© 2003 by The Society of Thoracic Surgeons

Despite recent progress in the medical treatment ofheart failure, mortality rates remain high in pa-

tients with New York Heart Association stage III and IVdisease. Almost 40% are dead 2 years, and more than 70%are dead 6 years after diagnosis [1]. In patients with NewYork Heart Association stage IV heart failure, the annualmortality rate is about 50% [2]. Heart transplantationcontributes to both functional improvement and survival.In our center, the survival of the first 281 transplantedpatients was 87% at 1 year, 77% at 5 years, and 57% at 10years. Age younger or older than 60 years did not affectsurvival [3].

Because donor organs are in increasingly short supply,wait lists are becoming longer. More urgent admissionsfor transplant patients requiring inotropic support hasled to an increase in urgent transplant operations. This,in turn, has required even more rigorous selection crite-

ria, increasing the pressure towards bridging by ventric-ular assist devices, which might increase transplantationmorbidity and mortality rates [4]. The purpose of thisretrospective study was to compare the morbidity andmortality rates among patients who had urgent hearttransplantation with those who had implantation ofbridging devices and those who waited at home forelective transplantation.

Patients and Methods

Study PopulationBetween March 1985 and December 2000, 404 patientshad heart transplantation, of whom 6 had retransplants.The following three groups were defined according to thefollowing UNOS status [5] categories: status 1A, criticallyill patients requiring continuous inotropic drug therapyor mechanical assistance and who have a life expectancyof less than 1 month without transplantation; status 1B,medically stable patients requiring mechanical assis-tance who have a life expectancy greater than 1 month(assisted circulation became available in our center in1988); and status 2, patients with chronic heart failurewho do not meet the higher urgency criteria for status 1Aor 1B.

Accepted for publication Jan 17, 2003.

Address reprint requests to Dr Baron, Unite de Transplantation Thora-cique, Service de Chirurgie Thoracique et Cardiovasculaire, Hopital G etR Laennec, 44093 Nantes, France; e-mail: [email protected].

© 2003 by The Society of Thoracic Surgeons 0003-4975/03/$30.00Published by Elsevier Inc PII S0003-4975(03)00163-2

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The decision to change from inotropic support (US 1A)to mechanical support (US 1B) was based on continuousclinical, echocardiographic, hemodynamic (cardiac in-dex, pulmonary artery pressure, and oxygen mixed ve-nous saturation), and biochemical (creatinine, bilirubin,and blood lactate level) evaluation of each unstablepatient hospitalized in an intensive care unit next to thecardiac surgery department.

Patients were characterized by age, sex, type of heartdisease, history of cardiac operations, obesity, history ofrenal insufficiency requiring dialysis, diabetes, neoplasm,serious infection, and presence or absence of completepretransplantation cancer assessment. We noted thepresence of donor seropositivity and recipient seronega-tivity for cytomegalovirus (CMV) and toxoplasmosis.Preoperative hemodynamic data consisted of mean pul-monary artery pressure, pulmonary capillary wedgepressure, pulmonary vascular resistance, and cardiacindex. Transplantation waiting time was defined as theinterval between placement on the waiting list and theday of transplantation. Transplant quality criteria weredefined by the donor’s age and heart ischemia time.Cardiopulmonary bypass time was recorded.

Patients were excluded as candidates for transplanta-tion according to generally accepted criteria [6]. Absolutecontraindications were (1) pulmonary hypertension withpulmonary vascular resistances higher than 6 Wood units(WU) and remaining higher than 3.5 WU after pharma-cologic tests (Enoximone, vasodilators, and nitric oxidetest), (2) neoplastic disease during the previous 5 years,(3) recent uncontrolled infection, or (4) other severeorgan failure. According to their degree of severity,relative contraindications were insulin-dependent diabe-tes mellitus, renal or hepatic insufficiency, and pulmo-nary disease.

Transplant TechniqueThe operative technique, chosen by preference of theoperator, was total or subtotal cardiectomy in 215 pa-tients (53.2%) and the Stanford technique in the other 189patients (46.8%). The donor heart was preserved withBretschneider solution in 264 patients (65.4%) and Celsiorsolution in 140 patients (34.6%). Immunosuppressivetherapy was the same in the three groups and consistedof antilymphocyte globulins for 3 to 5 days followed by acombination of cyclosporine, corticosteroids, and aza-thioprine, and, more recently, by mycophenolate mofetilor tacrolimus. Patients underwent endomyocardial bi-opsy weekly for 6 weeks after transplantation, then every2 weeks until the third month, and then every 6 weeksuntil the 6 month. Biopsies were also performed at theninth month, the 12th month, and then yearly. Rejectionseverity was grade 0 to 4 according to the InternationalSociety for Heart and Lung Transplantation gradingsystem. Grade 2 was managed with an increase in oralsteroids or cyclosporine. Intravenous bolus steroid ther-apy (500 mg/day � 5 days) was given for grade 3A orgreater. If a follow-up biopsy performed 10 days there-after showed no improvement, antilymphoblast globulin

was administered. Coronary angiography was performedevery other year to monitor transplant coronary disease.

Postoperative DataWe recorded postoperative infections, reoperations, totalhospital stay (in the intensive care unit and in the wardbefore hospital discharge), number of episodes of treatedacute rejection (at least grade IB according to the Inter-national Classification), and the incidences of cancer andtransplant coronary artery disease. Survival curves wereestablished from overall mortality, including operativemortality.

Statistical AnalysesTo calculate differences between groups, we used a �2

test for comparison of qualitative and discrete numericalvariables. A Kruskall-Wallis test was used for multiplecomparisons of quantitative variables among the threegroups, and a Mann-Whitney test was used to identifythe differences among the groups

To calculate the mortality rate within each group, thefactors associated with both in-hospital and late mortalitywere assessed first by univariate analysis using Fischer’sexact test and the Mann-Whitney test when appropriate.A second evaluation by logistic regression analysis in-cluded variables with p less than 0.1 in the univariateanalysis.

The overall mortality rate was analyzed by the Kaplan-Meier method. A log-rank test was performed to com-pare probabilities when possible. A Cox model was usedto test the role of covariates. A proportional hazardmodel was fit to the observed data using the variablesextracted from the univariate analysis as covariates, withthe three UNOS status groups to stratify the model. Thenatural logarithm of the cumulative base line hazardsplots for UNOS status was examined to look for theparallelism of the three curves (ie, indicating the propor-tionality of the hazard functions when the covariateswere included). When the proportionality was assumedto be present, the UNOS status was reassigned as acovariate. In the absence of proportionality, the analysiswas stopped and no conclusion could be drawn. After theanalysis, the relative hazards were estimated.

Results

PopulationIn the US 2 group, there were 273 patients (67.6%), ofwhich 234 were male and 39 female. The mean age was 51� 11 years (range, 12 to 67 years). The mean waiting timebefore transplantation was 66 � 68 days.

In the US 1A group, there were 103 patients (25.5%)who were waiting for transplant in the hospital and weregiven (separately or in combination) inotropic drugs,intraaortic balloon pump, or centrifugal pump (Biomedi-cus). There were 91 men and 12 women, and the meanage was 47 � 15 years (range, 12 to 66 years). The meanwaiting time before transplantation was 23 � 29 days. Anindication for urgent heart transplantation was decided

1879Ann Thorac Surg BARON ET AL2003;75:1878–85 UNOS STATUS AND TRANSPLANT PROGNOSIS

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in 42 patients (40.8%) who were already waiting fortransplantation but also in 61 (59.2%) new patients whopresented with a first episode of acute decompensationfrom heart disease. Indications included heart failurerefractory to maximum medical treatment in 79 cases(76.7%), rhythmic instability with severe arrhythmias in23 (22.3%), and unstable ischemia in 1 (1%). Eighty-five ofthese patients were treated with dobutamine (82.5%),which was associated with Enoximone in 52 patients(50.5%) and intraaortic balloon pump in 9 patients (8.7%).Four patients were treated with a Biomedicus centrifugalpump (3.9%) for a mean of 8 days (range, 3 hours to 11days). Three of these patients required left ventricularassistance, and one required biventricular ventricleassistance.

In the US 1B group, there were 28 patients (6.9%) whohad long-term ventricular assistance (16 Cardiowest, 7Novacor, 5 double Thoratec) with a mean waiting time of69 � 65 days to transplantation. All these patients weremale with a mean age of 41 � 11 years (range, 16 to 61years). Twenty-two (78.6%) presented with a first episodeof acute decompensation of heart disease (myocardialinfarction, rapid destabilization of dilated cardiomyopa-thy), and the possibility of transplantation had not beenpreviously proposed.

Table 1 summarizes the preoperative data. Patients inUS 1B were younger than those in US 1A and US 2, butsex distribution, initial heart disease, and medical historydid not differ among the three groups. The pretransplan-tation cancer assessment was more often incomplete inUS 1A (43.7%) and US 1B (60.7%) than in US 2 (1.8%) (p� 0.001 between US 2 and US 1A or 1B). At least onepreoperative infection was identified in 1.1% of patientsin US 2, 29.1% in US 1A, and 57.1% in US 1B (p � 0.0001between US 2 and US 1A or 1B; p � 0.05 between US 1Aand 1B).

The waiting time to transplant was significantly shorterin US 1A (23 � 29 days versus 66 � 68 days in US 2 and69 � 65 days in US 1B).

Preoperative Hemodynamic VariablesMean pulmonary artery pressure (mm Hg) was 29 � 10,33 � 9, and 34 � 9 for US 2, 1A, and 1B, respectively (p �0.001 US 2 versus 1A; p � 0.05 US 2 versus 1B; and p �0.05 between US 1A and 1B). Pulmonary capillary wedgepressure (mm Hg) was 20 � 9, 23 � 8, and 25 � 8 for US2, 1A, and 1B, respectively (p � 0.001 US 2 versus 1A; p �0.05 US 2 versus 1B; and p � 0.05 between US 1A and 1B).Cardiac index (l · min�1 · m�2) was 2.22 � 0.75, 2.11 � 1.8,and 2.05 � 0.64 for US 2, 1A, and 1B, respectively (p � 0.05between groups). Pulmonary vascular resistance (WU)was 2.44 � 1.3, 2.9 � 1.8, and 2.6 � 1.8 for US 2, 1A, and1B, respectively (p � 0.05 between groups).

TransplantNo statistically significant differences were found be-tween US 2, 1A, and 1B, respectively, for donor’s age(years) (30 � 10, 29 � 10, and 27 � 10), donor’s sex (M/F)(215/58, 82/2, and 24/4), transplant ischemia time (min-utes) (157 � 43,166 � 48, and 166 � 40), CMV mismatches(16.1%, 13.6%, and 21.4%), and toxoplasmosis mis-matches (9.1%, 11.6%, and 10.7%). Cardiopulmonary by-pass time (minutes) was 112 � 29, 113 � 29, and 146 � 70for US 2, 1A, and 1B, respectively (p � 0.001 US 2 versus1B; p � 0.008 US 1A versus 1B; and p � 0.05 between US2 and 1A).

Hospital Morbidity Rate and Length of StayNo statistically significant differences were found amongUS 2, 1A, and 1B, respectively, for tamponade, hemor-rhage requiring drainage operations (23.4%, 18.4%, and14.3%, respectively), presence of right heart failure

Table 1. Preoperative Characteristics

US 2(n � 273)

US 1A(n � 103)

US 1B(n � 28)

p Value

2 vs 1A 2 vs 1B 1A vs 1B

Age (years) 51 � 11 47 � 15 41 � 11 NS �0.001 �0.05Sex (M/F) 234/39 91/12 28/0 NS NS NSHeart disease etiology (%) NS NS NS

DCM 45.8 45.6 53.6Ischemic 37 44.6 42.9Valvular 4.8 1.9 3.6Other 10.6 6.8 0Retransplantation 1.8 0.9 0

History (%) NS NS NSObesity 6.2 2.9 7.1Diabetes 8.8 8.7 3.6Infection 7.3 5.8 3.6Renal insufficiency 5.9 2.9 7.1Cancer 3.7 5.8 7.1

Complete cancer assessment (%) 98.2 56.3 39.3 �0.0001 �0.0001 NSPreoperative sepsis (%) 1.1 29.1 57.1 �0.0001 �0.0001 �0.05Transplant waiting time (days) 66 � 68 23 � 29 69 � 65 �0.0001 NS �0.001

DCM � dilated cardiomyopathy; NS � not significant; US � UNOS status.

1880 BARON ET AL Ann Thorac SurgUNOS STATUS AND TRANSPLANT PROGNOSIS 2003;75:1878–85

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(21.6%, 18.4%, and 7.1%, respectively), renal failure re-quiring dialysis (4.7%, 3.9%, and 3.7%, respectively), andincidence of acute rejection episodes (0.7%, 1.9%, and3.5%, respectively). Mean intensive care unit and totalhospital length-of-stay were comparable (9.3 � 5.7 daysand 32.1 � 12 days for US 2; 9.5 � 7 days and 32.5 � 12.8days for US 1A; and 8.8 � 6.3 days and 37.1 � 13 days forUS 1B, respectively).

InfectionsThirty (29.1%) of the 103 patients in US 1A and 16 (57.1%)of the 28 patients of US 1B had been treated for at leastone infection before transplantation. These infectionshad been controlled by appropriate antibiotics and didnot represent a contraindication to transplantation. Post-operative infections also developed in 9 patients in US 1A(8.7%) , four of which were caused by the same organismisolated preoperatively. Postoperative infection also de-veloped in 5 patients in US 1B (17%). Seven (25%)patients in US 1B had an infection related to the ventric-ular assist device (power supply, Novacor abdominalpouch). None of these infections were responsible forposttransplantation complications. Three (1.1%) patientsin US 2 with preoperative infection had a differentinfection after transplantation.

The posttransplantation infection rate was not signifi-cantly different among the three groups (96 patients inUS 2 [35.1%], 39 patients in US 1A [37.8%], and 12patients in US 1B [42.8%]). Table 2 shows the etiologies ofinfections before and after transplantation. Toxoplasmainfections occurred in 1 patient with positive pretrans-plantation serology and in 2 seronegative patients graftedwith a seropositive donor.

Seven patients (1.7%) died during the postoperativeperiod, 6 from septic shock (bacterial septicemia in 5 andAspergillus septicemia in 1) and 1 from myocardialtoxoplasmosis.

Episodes of Acute Rejection Per PatientThe number of acute rejection episodes per patient was1.4 � 1.4, 1.3 � 1.3, and 1.3 � 1.2 for the first posttrans-plantation year for US 2, 1A, and 1B, respectively. Inyears following the first, the number of acute rejectionepisodes per patient was 0.17 � 0.7, 0.13 � 0.4, and 0.11 �0.1 for US 2, 1A, and 1B, respectively. There were nosignificant differences among groups for either period.

CancerThere were 68 patients in US 2 (24.9%) who developed atleast one cancer after transplantation (mean posttrans-plant interval, 56.2 � 34.2 months), compared with 22patients in US 1A (21.3%) after a mean interval of 62.1 �47.4 months, and 3 patients in US 1B (10.7%) after a meaninterval of 72.6 � 59.7 months. Kaplan-Meier cancer-freesurvival curves are shown in Figure 1. No statisticallysignificant difference was observed among the threegroups. Table 3 summarizes the types of cancers. Squa-mous cell carcinomas, adenocarcinomas, and lymphomaswere the three most frequent diagnoses. Some patientshad recurrent cutaneous carcinomas. A patient with

surgically treated carcinoma of the colon, thought to betumor-free by pretransplant assessment, had recurrentcarcinoma 52 months after transplantation.

Transplant Coronary Artery DiseaseKaplan-Meier transplant coronary artery disease-freesurvival curves are shown in Figure 2. No statisticallysignificant difference was found between the threegroups. Transplant coronary artery disease-free survivalat 6 years was 81.2% � 3%, 75.5% � 6%, and 61% � 5% forUS 2, 1A, and 1B, respectively.

Operative and Long-Term Mortality RatesThe in-hospital mortality rate was 7.7%, 7.8%, and 17.8%for US 2, 1A, and 1B, respectively, with no statisticallysignificant differences among the groups. The causes ofearly deaths are listed in Table 4. Univariate analysis

Table 2. Etiologies of Infections Before and AfterTransplantation

US 2 US 1A US 1B

Pretransplantation

Ear, nose, throatSinusitis 1 1 1Tonsillitis 1

RespiratoryPulmonary 2 4 3Bronchial 1

Urinary – 13 3Septicemia – 11 3Related to assist device

Power supply – – 3Novacor abdominal pouch – – 4

MiscellaneousGiardiasis – 1 –Anal fistula – 1 –Epididymo–orchitis – 1 –

Posttransplantation

BacterialLung infection 39 14 2Septicemia 29 (4) 9 (1) 7Urinary tract infection 19 9 1Peritonitis 2 2 –Renal transplant site 1

Virala

CMV 20 7 1Herpes group virus 4 2

ParasiticMyocardial toxoplasmosis 1 2 (1)Candidiasis 4 1Aspergillosis 1 (1)Giardiasis 1

a Viral infections were either primary infections or reactivations.

The number of infections responsible for death is indicated in parenthe-ses.

CMV � cytomegalovirus; US � UNOS status.


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demonstrated that ischemic heart disease (p � 0.048),cardiopulmonary bypass time (p � 0.008), postoperativeacute rejection (p � 0.001), and right heart failure (p �0.002) in US 2; cardiopulmonary bypass time (p � 0.048)and postoperative acute rejection (p � 0.003) in US 1A;and postoperative acute rejection (p � 0.001) in US 1Bwere the only variables associated with increased oper-ative mortality. Using multivariate analysis, right heartfailure (p � 0.005; odds ratio [OR] � 0.76 with 95%confidence interval [CI] � 0.85 to 0.67) was the onlyvariable associated with increased mortality in US 2, andno variables were associated with increased operativerisk in the two other groups.

The causes of long-term mortality are listed in Table 5.Univariate analysis demonstrated an association be-tween long-term mortality and donor’s age (p � 0.035),preoperative pulmonary artery pressure (p � 0.042),transplant ischemia time (p � 0.008), numerous episodesof acute rejection during and after the first postoperative

year (p � 0.025 and 0.021, respectively), the rate of cancer(p � 0.001), and the disease-free interval between trans-plantation and cancer (p � 0.04) in US 2; the rate of cancer(p � 0.001), numerous episodes of acute rejection duringthe first postoperative year (p � 0.001), and recipient’sage (p � 0.043) in US 1A; and transplant ischemia time(p � 0.049) in US 1B. Using multivariate analysis, vari-ables associated with long-term mortality were donor’sage (p � 0.035; OR � 0.909; CI � 0.83 to 0.99) and the rateof cancer (p � 0.035, OR � 0.97; CI � 0.93 to 0.99) in US 2;numerous episodes of acute rejection during the firstpostoperative year (p � 0.001; OR � 10.3; CI � 2.6 to 40.4)and the rate of cancer (p � 0.013, OR � 4.46; CI � 1.4 to14.4) in US 1A; and no variables associated with in-creased long-term mortality in US 1B.

Long-Term SurvivalFigure 3 shows the similarity of the Kaplan-Meier actu-arial survival curves of groups US 1A, 1B, and 2. In thosegroups, the 1-year survival rate was, respectively, 89.7%� 3.1%, 77.4% � 8.1%, and 86.4% � 2.1%; 3-year survivalwas 86.3% � 3.5%, 77.4% � 8.1%, and 82.7% � 2.4%;6-year survival was 81.4% � 4.3%, 77.4% � 8.1%, and76.3% � 2.8%; and 9-year survival was 71.5% � 6.0%,64.5% � 13.6%, and 65.1% � 3.7%.

Cox ModelInitially, age, transplant waiting time, and preoperativesepsis were used as covariates with UNOS groups tostratify the model. As illustrated in Figure 4, the curveswere not parallel, and we could not therefore assume that

Fig 1. Kaplan-Meier cancer-free survival curves. US � UNOS sta-tus.

Table 3. Etiologies of Cancers After Transplantation

US 2 US 1A US 1B

Squamous cell carcinomaSkin 42 (1) 10 (1) 3Lung 1 (1) 1 (1) –Head and neck 3 (1) 4 (1) –Gastrointestinal 1 (1) 1 –Gynecological 1 – –

AdenocarcinomaLung 5 (5) 1 (1) –Gastrointestinal 9 (4) 5 –Prostate 1 – –

Lymphoma 12 (8) 5 –Small cell lung cancer 1 (1) – –Neuroendocrine tumors 1 (1) – –Leukemia 1 (1) 2 (1) –Kaposi sarcoma of skin 1 1 –Meckel tumor – 1 (1) –Urothelial tumor 2 1 –

The number of cancers responsible for death is indicated in parentheses.

US � UNOS status.

Fig 2. Kaplan-Meier transplant coronary artery disease-free survivalcurves. US � UNOS status.

Table 4. Causes of In-Hospital Death

US 2(n � 273)

US 1A(n � 103)

US 1B(n � 28)

Graft dysfunction (%) 4.4 2.9 7.1Acute rejection (%) 0.7 1 3.6Sepsis (%) 2.2 2.9 –Miscellaneous (%) 0.4 1 7.1

Total (%) 7.7 7.8 17.8

US � UNOS status.


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the hazard functions for all three groups were propor-tional. The two curves representing US 2 and 1A, how-ever, were approximately parallel, suggesting propor-tionality between hazard functions and the possibility ofincluding group as a covariate in a model comparing US2 with 1A. Consequently, we reassigned group as acovariate after excluding the patients in US 1B. Theresults showed that age was the only covariate that couldaffect the hazards significantly (p � 0.013; estimate �0.032; standard error � 0.013).

Comment

Despite poorer hemodynamics and fewer complete pre-transplantation cancer assessments in patients in groupsUS 1A and US 1B, survival was comparable to that ofstable patients awaiting elective transplantation (US 2),even as the proportion of patients in US 1A and 1Bincreased with time. In 1985, patients classified as US 1Aor 1B comprised only 21.5% of our transplant recipients.By 2002, one third of our patients (32.4%) belonged tothese higher-risk groups. The survival results reportedhere are similar to those of patients who have received aventricular assist device while awaiting transplantation[7, 8]. Early experiences with urgent transplantation wereassociated with a 10% to 20% higher mortality rate at 1year [9, 10], although differences in study populations,definitions, and endpoints make comparisons difficult. Inthe late 1980s, Loisance and colleagues [11] reported a1-year survival rate of 52% in patients transplanted forrefractory heart failure with pharmacologic or ventricularassistance bridge, compared with 76% in patients who

were stable before transplantation. Stevenson and asso-ciates [12] reported a 1-month mortality rate of 12% in 50patients who had urgent transplantation compared with3% in 137 patients who had elective transplantation. Thelatest studies report survival rates of 86% at 1 year and80% at 3 years in patients transplanted after a ventricularassist device bridge [7], a significant improvement overearlier results [8, 13]. The role of urgent heart transplan-tation or the use of a ventricular assist device bridge totransplantation remains controversial. In a series of 234patients, univariate analysis showed that patients waitingfor transplantation at home had a lower mortality ratethan those hospitalized and requiring positive inotropicor ventricular assist device bridge [13]. Multivariate anal-ysis demonstrated that increased pulmonary vascularresistance was an independent factor predictive of poorprognosis. Conversely, McCarthy and coworkers [8]showed that ventricular assist device bridge before trans-plantation was not a risk factor for mortality after trans-plantation. Another study found a lower (57%) 5-yearsurvival rate in patients treated with a ventricular assistdevice bridge before transplantation, compared withpatients waiting at home (78%) or those receiving medi-cal treatment in the hospital (74%) [14].

Several factors can explain our results. We believe that

Table 5. Causes of Late Death

US 2(n � 252)

US 1A(n � 95)

US 1B(n � 23)

Infection (%) 2.8 1 –Cancer (%) 9.5 7.4 –Transplant coronary disease (%) 4.8 2.1 4.3Miscellaneous (%) 6 4.2 4.3

US � UNOS status.

Fig 3. Kaplan-Meier actuarial annual sur-vival in the three groups.

Fig 4. Kaplan-Meier estimation.


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the use of phosphodiesterase inhibitors, either alone orin combination with dobutamine and dopamine, andassisted circulation (introduced in 1988) has been impor-tant. Phosphodiesterase inhibitors, especially Enoxi-mone, which was used in 52 of the 103 patients in US 1A(50.5%), provide a real medical bridge by means of theirinotropic action on the myocardium together with adirect pulmonary and systemic vasodilator effect [15].Pretransplantation use of phosphodiesterase also im-proves patient selection by determining the degree towhich pulmonary hypertension is reversible.

In the treatment of cardiogenic shock, we have foundthat early institution of maximal inotropic support ismore effective than a regimen of incremental increases indosage. Furthermore, consideration of single or doubleventricular mechanical support remains an option in theevent of continued hemodynamic instability or deterio-ration. Timing is critical in the treatment of these pa-tients, and the decision to replace purely medical treat-ment by assisted circulation must not be considered a lastresort, but rather one of the available treatment optionsfor heart failure while awaiting transplantation [16].Since 1988, we have transplanted 28 patients after abridge by assisted circulation (Thoratec, Novacor, orCardiowest).

The decision to implant a ventricular assist device isbased on several indices [17], including systemic bloodpressure, hemodynamic surveillance by Swan-Ganzcatheter, hourly diuresis, and laboratory surveillance ofrenal and liver function. Pifarre and colleagues [18] andReedy and colleagues [19] found an improvement in1-month and 1-year survival rates in patients trans-planted after assisted circulation compared with theiroverall population of heart transplant recipients. In ourseries, the survival rate of patients transplanted afterventricular assist device was comparable to that of pa-tients waiting at home. Massad and associates [20] re-ported similar results in a study of 53 urgently trans-planted patients from a population of 256 transplantrecipients.

In our series, cardiopulmonary bypass time was longerand operative mortality rate higher in US 1B than in US2 or 1A, perhaps reflecting the presence of severe inflam-matory adhesions associated with the presence of me-chanical support devices. Of the five operative deaths inUS 1B, three were encountered early in our Novacor andThoratec experience. We have since learned to initiatecardiopulmonary bypass by femoral cannulation and todiscontinue ventricular assist device pumping beforesternotomy. Despite the increased operative risk, me-chanical assistance appears to protect patients from post-transplant right ventricular failure (right heart failurewas an operative mortality risk factor only in US 2). Weconclude that the use of phosphodiesterase inhibitorsand mechanical assist devices were protective of postop-erative right ventricular function in groups 1A and 1B.

Hemodynamic stabilization allows a more completepretransplantation assessment. In our series, however, 62of the 131 patients transplanted urgently or after ventric-ular assist device implantation (47.3%) had incomplete

pretransplantation assessment. Nevertheless, we did notlater discover any cancers that could have been detectedbefore transplantation. Postoperative infection continuesto be a problem in transplantation, but we found nosignificant differences in incidence among the threegroups. Although the waiting time was significantlyshorter in the group of urgently transplanted patients,donor age and transplant organ ischemia time werecomparable in the three groups. Because the supply ofdonor hearts is limited, we sometimes accept transplantsfrom older donors, but there were no differences amongthe groups. The influence of the transplant ischemia time(greater than 240 minutes) on the results of transplanta-tion is controversial [21, 22], and the use of transplantsfrom older donors is responsible for an increased post-operative mortality [23].

Urgent transplantation or transplantation after bridg-ing with a ventricular assist device did not have anyinfluence on the surgical technique used or on postoper-ative complications requiring reoperation, althoughcardiectomy was longer and more difficult in patientswho had circulatory assistance. There was no significantdifference among the three groups with respect to thenumber of episodes of acute rejection during the firstyear and beyond. Preoperative hemodynamic instabilityand its consequences (renal insufficiency, sepsis) did notinfluence the quality of immunosuppression.

In our practice, the number of patients transplantedurgently or after bridging by ventricular assist deviceincreases each year. Because the hospital morbidity andlong-term survival rates in these patients are comparableto those of patients waiting at home, we are encouragedto continue this protocol. We emphasize the timelyreferral of patients in cardiogenic shock to a team expe-rienced in assisted circulation techniques, should theybecome refractory to optimal medical treatment. Controlof pretransplant nosocomial infection is obvious butnecessary. The major practical obstacle to the growth ofurgent transplantation is the decreasing availability oforgans. The use of transplants from older donors may beinevitable, but it is likely to be associated with increasedoperative mortality rates. The more frequent applicationof assisted circulation as a bridge to transplantation isalso inevitable because of longer waiting lists. Until apermanent implantable ventricular assist device be-comes available, urgent transplantation or transplanta-tion after temporary mechanical ventricular assistanceprovides acceptable results if candidates are chosen bycarefully defined criteria.

Many thanks to Dr Philippe Bizouarn for statistical assistanceand advice. We are indebted to Dr Ronald Weintraub for hisassistance in the preparation of this manuscript.

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does the pretransplant unos status modify the short- and long-term cardiac transplant prognosis?

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