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Abstract

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OBJECTIVES

Heart transplantation (HT) is the only life-extending therapy in adults with congenital heart disease (CHD) and end-stage heart failure. HT is considered at high risk in complex CHD given the anatomical complexity and past medical history. Little is known about long-term outcomes after HT in these patients. We aimed to evaluate early and long-term outcomes after HT in adult patients with univentricular versus biventricular CHD.

METHODS

This multicentre retrospective cohort study included all adult CHD patients who underwent HT between 1988 and 2021 in 3 tertiary centres. Factors associated with early (<30 days) and conditional long-term survival were assessed in the entire cohort.

RESULTS

Over a mean follow-up of 10.1 ± 7.8 years, 149 patients were included, of whom 55 (36.9%) had univentricular CHD. Sixty-four patients died during follow-up including 47 deaths before discharge from hospital. In multivariable analysis, univentricular physiology and female recipient gender were independently associated with a higher risk of early mortality (odds ratio 2.99; 95% confidence interval [1.33–6.74] and odds ratio 2.76; 95% confidence interval [1.23–6.20], respectively). For patients who survived the early period, conditional long-term survival was excellent for both groups and was not different between 2 groups (P = 0.764).

CONCLUSIONS

Adult CHD patients have a high incidence of overall mortality due to a high rate of early mortality. Univentricular physiology was associated with a significant increased risk of early death compared to biventricular physiology. However, late mortality was excellent and no longer different between the 2 physiologies.

Adult congenital heart disease, Heart transplantation, Cardiac physiology

INTRODUCTION

With the advances in congenital cardiology and surgery, the majority of children with congenital heart disease (CHD), even those with complex lesions, now reach adulthood [1]. However, as CHD patients live longer, the combination of birth heart defects and changes resulting from successive surgeries leads patients to cardiac dysfunction [2]. Heart failure (HF) is the leading cause of death in this population [3] and its incidence ranges from 26% to 42% [4, 5]. Unlike non-CHD patients, the management of HF in CHD patients is more challenging because of the heterogeneity of their cardiac defects, prior surgical repairs, and the lack of evidence for conventional HF treatment [6]. Heart transplantation (HT) remains the only life-extending treatment for end-stage HF. However, mixed results were obtained. The heterogeneity and complexity of anatomical lesions, the large number of previous surgeries, the associated organ failures and the hyperimmunization expose to high surgical risk [7]. Several studies have shown a change of trends in the complexity of CHD, notably an expected increase in univentricular patients in future years [8], but also in the patients candidates to HT [9]. Indeed, we have previously reported that over the period 1988–2012, the complexity of CHD patients referred for HT had increased with nearly half of them presenting with univentricular physiology often associated with multi-organ dysfunction [10]. In addition, the International Society for Heart and Lung Transplantation and the United Network for Organ Sharing reports demonstrated an increase of HT [11, 12] in CHD, including patients with chronic renal failure that doubled in 10 years [13].

However, high-volume multicentre studies with long follow-up duration and detailed data are scarce, and few studies worldwide address transplantation outcomes in patients with univentricular versus biventricular CHD.

Therefore, we conducted a multicentre study to describe and compare the characteristics and outcomes in adult congenital heart disease (ACHD) patients who underwent HT according to the physiopathological models of repair, i.e. univentricular or biventricular status.

METHODS

Ethics statement

The collection and analysis of data for this study were approved by institutions’ local ethics committees (IRB 00012157) and a waiver of individual patient consent was obtained on the basis of data anonymity. In accordance with the Transparency and Openness Promotion Guidelines, the data that support the findings of this study are available from the corresponding author on reasonable request.

Study population and data collection

We identified and studied retrospectively all consecutive patients with CHD aged ≥16 years who underwent primary HT at 3 centres in Paris (France) between May 1988 and May 2021. This cut-off corresponds to the age in which minor patients may be managed within an adult hospital in France. Two of these centres are specialized in ACHD care while the third is a generalized but high-volume centre. Patients who underwent multi-organ transplantation were excluded from this study. Donor and recipient demographic, preoperative and postoperative variables were collected. Initial cardiac diagnosis, clinical history, prior cardiac surgeries, HT procedure, survival and morbidity were retrieved from hospital medical records. In 2004, the French cardiac allocation system evolved and granted priority status to patients on inotrope support or short-term MCS and to candidates on long-term MCS with device-related complications [14]. More recently, in 2018, the Agence de la Biomédecine developed a new heart transplant allocation model derived from a calculable candidate risk score (CRS) based on candidates' characteristics. Exceptions to the CRS-based allocation system are allowed for the subcategories of candidates for whom the CRS seems to be an inappropriate measure of urgency as paediatric candidates, patients on long-term MCS with device-related complications, and patients with contraindication to VAD implantation. We defined the variable ‘Priority HT listing’ as a transplant performed in the context of priority according to the current allocation rules [15].

Outcomes of interest and surgical techniques

The primary outcome was the early mortality and the post-HT complications. The different causes of death after HT were also collected and compared. Early mortality was defined as death within 30 days following HT or during the index hospitalization. Conditional long-term survival was defined as survival given that the patient has already survived the early period ie survived the index hospitalization. The secondary outcome was late mortality defined as death occurring after the early period. Post-HT complications such as humour or cellular rejection, dialysis, cancer or graft coronary disease were also assessed. Our study cohort was divided into 2 groups according to the cardiac pathophysiology, i.e. univentricular and biventricular repair.

All patients were implanted orthotopically through a median sternotomy and using a cardiopulmonary bypass (CPB). Two surgical techniques were used either the bi-atrial technique for the oldest or bicaval technique for the latest ones. In case of lack of tissue mainly for the pulmonary artery (PA), a PA reconstruction was performed either by autologous pericardium patch and by xenograft pericardium patch.

The choice of the immunosuppressive treatment was left to the discretion of the clinicians according to the guidelines. Dedicated cardiologist followed patients every 6 months after discharge.

Statistical analysis

Continuous variables were expressed as mean ± standard deviation or median and interquartile range (25th to 75th percentile), based on the normality of distribution. Categorical variables were presented as frequencies and percentages. Characteristics of the 2 groups (according to the initial physiology) were compared using Student’s t-test and chi-square (or Fischer exacts tests, as appropriate) for continuous and categorical variables, respectively.

Survival curves were generated using Kaplan–Meier estimates and the log rank test was performed to determine the difference between strata. The Kaplan–Meier analysis conditioned by surviving the early post-transplantation period accounted for left truncation.

Considering the primary outcome, logistic regression analysis was performed to identify risk factors for early mortality. Considering the secondary outcome, univariable analyses were conducted by using a Cox proportional hazard model to identify potential prognostic factors of mortality and to estimate adjusted hazard ratios and their 95% confidence interval (CI). To consider confounders of survival analysis, a multivariable analysis was performed by using a Cox proportional hazards model with forward stepwise selection of covariates and with entering and removing limits of P < 0.25 and P > 0.05. Values of P < 0.05 were considered statistically significant. Statistical analysis was conducted using IBM SPSS Statistics v18 software (IBM Corporation, Armonk, NY).

RESULTS

Patients’ characteristics

As summarized in a Graphical Abstract, a total of 149 patients transplanted between 1988 and 2021 were included in the study. Demographics and clinical patients’ characteristics are reported in Supplementary Material, Table S1. The mean age at HT was 33.2 ±11.7 years and 66.4% were male. There were 55 (36.9%) patients with univentricular physiology and 94 (63.1%) with biventricular physiology. Baseline characteristics according to physiological models of repair are compared in Table 1. Univentricular patients were transplanted younger and had a higher number of previous surgeries due to a higher number of thoracotomies compared to biventricular patients. Univentricular patients had lower oxygen saturation, higher haemoglobin concentration and haematocrit levels. They presented more preoperative supraventricular tachycardia. The mean CPB time and ischaemic time were significantly longer in the univentricular group (250.0 ± 128.3 vs 194.0 ± 86.4; P = 0.003 and 231.2 ± 67.0 vs 198.2 ± 63.0; P = 0.004, respectively).

Table 1:
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Baseline demographics, clinical characteristics and outcomes according to cardiac physiology at diagnosis (univentricular versus biventricular)

n (%) or mean ± standard deviationUniventricular n = 55 (%)Biventricular n = 94 (%)P-value
Recipient
 Age at listing (years)28.8 ± 10.034.9 ± 12.10.002
 Age at transplant (years)29.3 ± 9.935.4 ± 12.20.002
 Female sex23 (41.8)27 (28.7)0.110a
 Time on waiting list (days)191.8 ± 296.0186.2 ± 252.00.903
 Recipient BMI (kg/m2)21.0 ± 4.022.4 ± 4.20.051
Medical history
 History of previous surgery49 (90.7)88 (93.6)0.530b
 Number of previous surgery2.9 ± 1.62.3 ± 1.40.018
 More than 3 previous surgery35 (63.6)36 (38.3)0.003a
 Previous sternotomy1.9 ± 1.52.0 ± 1.30.931
 Previous thoracotomy1.0 ± 0.90.4 ± 0.5<0.001
 ICD before listing0 (0.0)26 (27.7)<0.001b
 CRT before listing6 (10.9)23 (24.5)0.044a
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle27 (49.1)58 (61.7)0.133a
 Previous SVT30 (54.6)34 (36.2)0.029a
 Protein-losing enteropathy6 (10.9)0 (0.0)0.002b
 Fistulae or collateral vessels8 (14.6)2 (2.1)0.005b
 Haematocrit (%)50.0 ± 10.039.1 ± 6.9<0.001
 Haemoglobin (g/dl)16.3 ± 3.313.1 ± 2.3<0.001
 Oxygen saturation (%)84.9 ± 9.495.7 ± 5.2<0.001
 Creatinine clearance <60 ml/min8 (14.6)19 (20.2)0.386a
 Priority HT listing14 (25.9)28 (30.1)0.588a
 At home before HT40 (72.7)57 (60.6)0.135a
 ECMO/VAD dependent before HT3 (5.5)20 (21.3)0.010b
 Inotrope-dependent before HT10 (18.2)25 (26.6)0.242a
 UNOS status 112 (21.8)33 (35.1)0.095a
Donor
 Female donor23 (42.6)38 (41.8)0.922a
 Age (years)35.3 ± 13.741.3 ± 13.90.012
 BMI (kg/m2)23.7 ± 4.424.7 ± 4.80.210
 Need for inotropic agent44 (80.0)75 (79.8)0.812a
Peri-operative data
 Ischaemic time (min)231.2 ± 67.0 198.2 ± 63.00.004
 Bypass time (min)250.0 ± 128.3194.0 ± 86.40.003
 Prior femoral cannulation10 (19.2)9 (9.8)0.108a
 Additional procedure22 (40.0)9 (9.6)<0.001a
 Haemostasis revision14 (25.5)24 (25.5)0.992a
Survival outcomes
 Death (overall)30 (54.6)34 (36.2)0.016a
 Post-HT VA-ECMO19 (34.6)28 (29.8)0.546a
 In-hospital mortality24 (43.6)23 (24.5)0.009a
 One-year mortality25 (45.5)25 (26.6)0.008a
Causes of death
 Graft dysfunction10 (18.2)9 (9.6)0.128a
 Haemorrhage7 (12.7)3 (3.2)0.025b
 Sepsis8 (14.6)5 (5.3)0.054b
 Stroke1 (1.8)2 (2.1)0.897b
 Rejection1 (1.8)1 (1.1)0.699b
 Others3 (5.5)13 (13.8)0.111b
Long-term outcomes
 Dialysis3 (5.5)2 (2.1)0.288b
 Re-heart transplantation2 (3.6)3 (3.2)0.903b
 Cancer3 (5.5)5 (5.3)0.972b
 Cellular rejection14 (25.5)25 (26.6)0.878a
 Graft coronary disease4 (7.3)5 (5.3)0.641a
 Humour rejection2 (3.6)2 (2.1)0.582a
n (%) or mean ± standard deviationUniventricular n = 55 (%)Biventricular n = 94 (%)P-value
Recipient
 Age at listing (years)28.8 ± 10.034.9 ± 12.10.002
 Age at transplant (years)29.3 ± 9.935.4 ± 12.20.002
 Female sex23 (41.8)27 (28.7)0.110a
 Time on waiting list (days)191.8 ± 296.0186.2 ± 252.00.903
 Recipient BMI (kg/m2)21.0 ± 4.022.4 ± 4.20.051
Medical history
 History of previous surgery49 (90.7)88 (93.6)0.530b
 Number of previous surgery2.9 ± 1.62.3 ± 1.40.018
 More than 3 previous surgery35 (63.6)36 (38.3)0.003a
 Previous sternotomy1.9 ± 1.52.0 ± 1.30.931
 Previous thoracotomy1.0 ± 0.90.4 ± 0.5<0.001
 ICD before listing0 (0.0)26 (27.7)<0.001b
 CRT before listing6 (10.9)23 (24.5)0.044a
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle27 (49.1)58 (61.7)0.133a
 Previous SVT30 (54.6)34 (36.2)0.029a
 Protein-losing enteropathy6 (10.9)0 (0.0)0.002b
 Fistulae or collateral vessels8 (14.6)2 (2.1)0.005b
 Haematocrit (%)50.0 ± 10.039.1 ± 6.9<0.001
 Haemoglobin (g/dl)16.3 ± 3.313.1 ± 2.3<0.001
 Oxygen saturation (%)84.9 ± 9.495.7 ± 5.2<0.001
 Creatinine clearance <60 ml/min8 (14.6)19 (20.2)0.386a
 Priority HT listing14 (25.9)28 (30.1)0.588a
 At home before HT40 (72.7)57 (60.6)0.135a
 ECMO/VAD dependent before HT3 (5.5)20 (21.3)0.010b
 Inotrope-dependent before HT10 (18.2)25 (26.6)0.242a
 UNOS status 112 (21.8)33 (35.1)0.095a
Donor
 Female donor23 (42.6)38 (41.8)0.922a
 Age (years)35.3 ± 13.741.3 ± 13.90.012
 BMI (kg/m2)23.7 ± 4.424.7 ± 4.80.210
 Need for inotropic agent44 (80.0)75 (79.8)0.812a
Peri-operative data
 Ischaemic time (min)231.2 ± 67.0 198.2 ± 63.00.004
 Bypass time (min)250.0 ± 128.3194.0 ± 86.40.003
 Prior femoral cannulation10 (19.2)9 (9.8)0.108a
 Additional procedure22 (40.0)9 (9.6)<0.001a
 Haemostasis revision14 (25.5)24 (25.5)0.992a
Survival outcomes
 Death (overall)30 (54.6)34 (36.2)0.016a
 Post-HT VA-ECMO19 (34.6)28 (29.8)0.546a
 In-hospital mortality24 (43.6)23 (24.5)0.009a
 One-year mortality25 (45.5)25 (26.6)0.008a
Causes of death
 Graft dysfunction10 (18.2)9 (9.6)0.128a
 Haemorrhage7 (12.7)3 (3.2)0.025b
 Sepsis8 (14.6)5 (5.3)0.054b
 Stroke1 (1.8)2 (2.1)0.897b
 Rejection1 (1.8)1 (1.1)0.699b
 Others3 (5.5)13 (13.8)0.111b
Long-term outcomes
 Dialysis3 (5.5)2 (2.1)0.288b
 Re-heart transplantation2 (3.6)3 (3.2)0.903b
 Cancer3 (5.5)5 (5.3)0.972b
 Cellular rejection14 (25.5)25 (26.6)0.878a
 Graft coronary disease4 (7.3)5 (5.3)0.641a
 Humour rejection2 (3.6)2 (2.1)0.582a
a

Chi-square test.

b

Fisher test.

BMI: body mass index; CRT: cardiac resynchronization therapy; ECMO: extracorporeal membrane oxygenation; HT: heart transplantation; ICD: implantable cardioverter defibrillator; SVT: supraventricular tachycardia; UNOS: United Network for Organ Sharing; VA: veno-arterial; VAD: ventricular assist device.

Table 1:
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Baseline demographics, clinical characteristics and outcomes according to cardiac physiology at diagnosis (univentricular versus biventricular)

n (%) or mean ± standard deviationUniventricular n = 55 (%)Biventricular n = 94 (%)P-value
Recipient
 Age at listing (years)28.8 ± 10.034.9 ± 12.10.002
 Age at transplant (years)29.3 ± 9.935.4 ± 12.20.002
 Female sex23 (41.8)27 (28.7)0.110a
 Time on waiting list (days)191.8 ± 296.0186.2 ± 252.00.903
 Recipient BMI (kg/m2)21.0 ± 4.022.4 ± 4.20.051
Medical history
 History of previous surgery49 (90.7)88 (93.6)0.530b
 Number of previous surgery2.9 ± 1.62.3 ± 1.40.018
 More than 3 previous surgery35 (63.6)36 (38.3)0.003a
 Previous sternotomy1.9 ± 1.52.0 ± 1.30.931
 Previous thoracotomy1.0 ± 0.90.4 ± 0.5<0.001
 ICD before listing0 (0.0)26 (27.7)<0.001b
 CRT before listing6 (10.9)23 (24.5)0.044a
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle27 (49.1)58 (61.7)0.133a
 Previous SVT30 (54.6)34 (36.2)0.029a
 Protein-losing enteropathy6 (10.9)0 (0.0)0.002b
 Fistulae or collateral vessels8 (14.6)2 (2.1)0.005b
 Haematocrit (%)50.0 ± 10.039.1 ± 6.9<0.001
 Haemoglobin (g/dl)16.3 ± 3.313.1 ± 2.3<0.001
 Oxygen saturation (%)84.9 ± 9.495.7 ± 5.2<0.001
 Creatinine clearance <60 ml/min8 (14.6)19 (20.2)0.386a
 Priority HT listing14 (25.9)28 (30.1)0.588a
 At home before HT40 (72.7)57 (60.6)0.135a
 ECMO/VAD dependent before HT3 (5.5)20 (21.3)0.010b
 Inotrope-dependent before HT10 (18.2)25 (26.6)0.242a
 UNOS status 112 (21.8)33 (35.1)0.095a
Donor
 Female donor23 (42.6)38 (41.8)0.922a
 Age (years)35.3 ± 13.741.3 ± 13.90.012
 BMI (kg/m2)23.7 ± 4.424.7 ± 4.80.210
 Need for inotropic agent44 (80.0)75 (79.8)0.812a
Peri-operative data
 Ischaemic time (min)231.2 ± 67.0 198.2 ± 63.00.004
 Bypass time (min)250.0 ± 128.3194.0 ± 86.40.003
 Prior femoral cannulation10 (19.2)9 (9.8)0.108a
 Additional procedure22 (40.0)9 (9.6)<0.001a
 Haemostasis revision14 (25.5)24 (25.5)0.992a
Survival outcomes
 Death (overall)30 (54.6)34 (36.2)0.016a
 Post-HT VA-ECMO19 (34.6)28 (29.8)0.546a
 In-hospital mortality24 (43.6)23 (24.5)0.009a
 One-year mortality25 (45.5)25 (26.6)0.008a
Causes of death
 Graft dysfunction10 (18.2)9 (9.6)0.128a
 Haemorrhage7 (12.7)3 (3.2)0.025b
 Sepsis8 (14.6)5 (5.3)0.054b
 Stroke1 (1.8)2 (2.1)0.897b
 Rejection1 (1.8)1 (1.1)0.699b
 Others3 (5.5)13 (13.8)0.111b
Long-term outcomes
 Dialysis3 (5.5)2 (2.1)0.288b
 Re-heart transplantation2 (3.6)3 (3.2)0.903b
 Cancer3 (5.5)5 (5.3)0.972b
 Cellular rejection14 (25.5)25 (26.6)0.878a
 Graft coronary disease4 (7.3)5 (5.3)0.641a
 Humour rejection2 (3.6)2 (2.1)0.582a
n (%) or mean ± standard deviationUniventricular n = 55 (%)Biventricular n = 94 (%)P-value
Recipient
 Age at listing (years)28.8 ± 10.034.9 ± 12.10.002
 Age at transplant (years)29.3 ± 9.935.4 ± 12.20.002
 Female sex23 (41.8)27 (28.7)0.110a
 Time on waiting list (days)191.8 ± 296.0186.2 ± 252.00.903
 Recipient BMI (kg/m2)21.0 ± 4.022.4 ± 4.20.051
Medical history
 History of previous surgery49 (90.7)88 (93.6)0.530b
 Number of previous surgery2.9 ± 1.62.3 ± 1.40.018
 More than 3 previous surgery35 (63.6)36 (38.3)0.003a
 Previous sternotomy1.9 ± 1.52.0 ± 1.30.931
 Previous thoracotomy1.0 ± 0.90.4 ± 0.5<0.001
 ICD before listing0 (0.0)26 (27.7)<0.001b
 CRT before listing6 (10.9)23 (24.5)0.044a
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle27 (49.1)58 (61.7)0.133a
 Previous SVT30 (54.6)34 (36.2)0.029a
 Protein-losing enteropathy6 (10.9)0 (0.0)0.002b
 Fistulae or collateral vessels8 (14.6)2 (2.1)0.005b
 Haematocrit (%)50.0 ± 10.039.1 ± 6.9<0.001
 Haemoglobin (g/dl)16.3 ± 3.313.1 ± 2.3<0.001
 Oxygen saturation (%)84.9 ± 9.495.7 ± 5.2<0.001
 Creatinine clearance <60 ml/min8 (14.6)19 (20.2)0.386a
 Priority HT listing14 (25.9)28 (30.1)0.588a
 At home before HT40 (72.7)57 (60.6)0.135a
 ECMO/VAD dependent before HT3 (5.5)20 (21.3)0.010b
 Inotrope-dependent before HT10 (18.2)25 (26.6)0.242a
 UNOS status 112 (21.8)33 (35.1)0.095a
Donor
 Female donor23 (42.6)38 (41.8)0.922a
 Age (years)35.3 ± 13.741.3 ± 13.90.012
 BMI (kg/m2)23.7 ± 4.424.7 ± 4.80.210
 Need for inotropic agent44 (80.0)75 (79.8)0.812a
Peri-operative data
 Ischaemic time (min)231.2 ± 67.0 198.2 ± 63.00.004
 Bypass time (min)250.0 ± 128.3194.0 ± 86.40.003
 Prior femoral cannulation10 (19.2)9 (9.8)0.108a
 Additional procedure22 (40.0)9 (9.6)<0.001a
 Haemostasis revision14 (25.5)24 (25.5)0.992a
Survival outcomes
 Death (overall)30 (54.6)34 (36.2)0.016a
 Post-HT VA-ECMO19 (34.6)28 (29.8)0.546a
 In-hospital mortality24 (43.6)23 (24.5)0.009a
 One-year mortality25 (45.5)25 (26.6)0.008a
Causes of death
 Graft dysfunction10 (18.2)9 (9.6)0.128a
 Haemorrhage7 (12.7)3 (3.2)0.025b
 Sepsis8 (14.6)5 (5.3)0.054b
 Stroke1 (1.8)2 (2.1)0.897b
 Rejection1 (1.8)1 (1.1)0.699b
 Others3 (5.5)13 (13.8)0.111b
Long-term outcomes
 Dialysis3 (5.5)2 (2.1)0.288b
 Re-heart transplantation2 (3.6)3 (3.2)0.903b
 Cancer3 (5.5)5 (5.3)0.972b
 Cellular rejection14 (25.5)25 (26.6)0.878a
 Graft coronary disease4 (7.3)5 (5.3)0.641a
 Humour rejection2 (3.6)2 (2.1)0.582a
a

Chi-square test.

b

Fisher test.

BMI: body mass index; CRT: cardiac resynchronization therapy; ECMO: extracorporeal membrane oxygenation; HT: heart transplantation; ICD: implantable cardioverter defibrillator; SVT: supraventricular tachycardia; UNOS: United Network for Organ Sharing; VA: veno-arterial; VAD: ventricular assist device.

The initial CHD diagnoses of patients are summarized in Table 2. Among the 55 patients with univentricular physiology, 31 were partially (partial cavopulmonary connection, PA banding, aortopulmonary shunt) or not palliated. The most common diagnosis for univentricular patients was tricuspid atresia and transposition of great arteries for biventricular patients. Figure 1 shows the proportion of HT in univentricular and biventricular patients per 3 years. Pre-transplant panel reactive antibodies were only available in 42 (28.2%) patients. Retrospective cross-matches were negative in all patients and prohibited antigens were absent in the donors.

Proportion of HT according to initial physiology per 3 years.
Figure 1:

Proportion of HT according to initial physiology per 3 years.

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Table 2:
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Congenital heart disease diagnoses and major physiology categories

Primary diagnosis, n (%)n (%)
2 V with systemic right ventricle37 (24.8)
 D-TGA (atrial switch)26 (17.4)
 Congenitally corrected TGA11 (7.4)
2 V with systemic left ventricle57 (38.3)
 TOF22 (14.8)
 Congenital valvular diseasea22 (14.8)
 Ventricular septal defect5 (3.4)
 Others (miscellaneous)6 (4.0)
 TOF with pulmonary atresia2 (1.3)
1 V partially or not palliated31 (20.8)
 Single ventricle12 (8.1)
 Double inlet left ventricle9 (6.0)
 Tricuspid atresia6 (4.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Congenitally corrected TGA1 (0.7)
 Congenital valvular diseaseb1 (0.7)
1 V with total cavopulmonary connection (Fontan-type circulation)24 (16.1)
 Tricuspid atresia13 (8.8)
 Single ventricle6 (4.0)
 Double inlet left ventricle3 (2.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Total149
Primary diagnosis, n (%)n (%)
2 V with systemic right ventricle37 (24.8)
 D-TGA (atrial switch)26 (17.4)
 Congenitally corrected TGA11 (7.4)
2 V with systemic left ventricle57 (38.3)
 TOF22 (14.8)
 Congenital valvular diseasea22 (14.8)
 Ventricular septal defect5 (3.4)
 Others (miscellaneous)6 (4.0)
 TOF with pulmonary atresia2 (1.3)
1 V partially or not palliated31 (20.8)
 Single ventricle12 (8.1)
 Double inlet left ventricle9 (6.0)
 Tricuspid atresia6 (4.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Congenitally corrected TGA1 (0.7)
 Congenital valvular diseaseb1 (0.7)
1 V with total cavopulmonary connection (Fontan-type circulation)24 (16.1)
 Tricuspid atresia13 (8.8)
 Single ventricle6 (4.0)
 Double inlet left ventricle3 (2.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Total149
a

Congenital valvular disease (n) included: Ebstein anomaly (3), other tricuspid regurgitation (1), congenital aortic stenosis (4), mitral stenosis (2) and mitral regurgitation (1).

b

Congenital valvular disease included an Ebstein anomaly.

TGA: transposition of the great arteries; TOF: tetralogy of Fallot; 1 V: univentricular physiology; 2 V: biventricular physiology.

Table 2:
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Congenital heart disease diagnoses and major physiology categories

Primary diagnosis, n (%)n (%)
2 V with systemic right ventricle37 (24.8)
 D-TGA (atrial switch)26 (17.4)
 Congenitally corrected TGA11 (7.4)
2 V with systemic left ventricle57 (38.3)
 TOF22 (14.8)
 Congenital valvular diseasea22 (14.8)
 Ventricular septal defect5 (3.4)
 Others (miscellaneous)6 (4.0)
 TOF with pulmonary atresia2 (1.3)
1 V partially or not palliated31 (20.8)
 Single ventricle12 (8.1)
 Double inlet left ventricle9 (6.0)
 Tricuspid atresia6 (4.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Congenitally corrected TGA1 (0.7)
 Congenital valvular diseaseb1 (0.7)
1 V with total cavopulmonary connection (Fontan-type circulation)24 (16.1)
 Tricuspid atresia13 (8.8)
 Single ventricle6 (4.0)
 Double inlet left ventricle3 (2.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Total149
Primary diagnosis, n (%)n (%)
2 V with systemic right ventricle37 (24.8)
 D-TGA (atrial switch)26 (17.4)
 Congenitally corrected TGA11 (7.4)
2 V with systemic left ventricle57 (38.3)
 TOF22 (14.8)
 Congenital valvular diseasea22 (14.8)
 Ventricular septal defect5 (3.4)
 Others (miscellaneous)6 (4.0)
 TOF with pulmonary atresia2 (1.3)
1 V partially or not palliated31 (20.8)
 Single ventricle12 (8.1)
 Double inlet left ventricle9 (6.0)
 Tricuspid atresia6 (4.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Congenitally corrected TGA1 (0.7)
 Congenital valvular diseaseb1 (0.7)
1 V with total cavopulmonary connection (Fontan-type circulation)24 (16.1)
 Tricuspid atresia13 (8.8)
 Single ventricle6 (4.0)
 Double inlet left ventricle3 (2.0)
 Pulmonary atresia with intact ventricular septum2 (1.3)
 Total149
a

Congenital valvular disease (n) included: Ebstein anomaly (3), other tricuspid regurgitation (1), congenital aortic stenosis (4), mitral stenosis (2) and mitral regurgitation (1).

b

Congenital valvular disease included an Ebstein anomaly.

TGA: transposition of the great arteries; TOF: tetralogy of Fallot; 1 V: univentricular physiology; 2 V: biventricular physiology.

Early mortality and outcomes

The mean follow-up time after HT was 10.1 ± 7.8 years excluding the early deaths and no patients were lost to follow-up. Sixty-four patients died during follow-up, including 47 deaths before discharge from hospital.

Early mortality was 32.5% (95% CI: 0.26–0.41). Of the 47 patients who died before being discharged, the cause of death was primary graft failure in 19 patients, haemorrhage in 10, sepsis in 9, stroke in 3 and others in 6 (Supplementary Material, Table S1).

A third of patients (n = 47, 31.5%) required postoperative venoarterial extracorporeal membrane oxygenation (VA-ECMO) and the mean VA-ECMO time was 9.6 ± 13.3 days (1–83). Among them, 18 patients (38.3%) survived after being discharged. Thirty-eight patients (25.5%) had a postoperative haemorrhage requiring surgical revision.

Early mortality was significantly higher (P = 0.009) in the univentricular group (n = 24, 43.6%) compared to the biventricular group (n = 23, 24.5%). The main causes of early mortality are presented in Table 1, with significantly more deaths due to haemorrhage in the univentricular group. The proportion of patients who needed post-HT VA-ECMO was not different.

Uni- and multivariable analyses of risk factors associated with early mortality in the study population are listed in Table 3. In multivariable analysis, female recipient gender (odds ratio: 2.99; 95% CI 1.33–6.74, P = 0.008) and univentricular physiology (odds ratio: 2.76; 95% CI 1.23–6.19, P = 0.014) were independently associated with higher risk of early mortality.

Table 3:
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Factors associated with early mortality in binary logistic regression analyses

VariableUnivariable analysis
Multivariable analysis
OR (95% CI)P-valueAdjusted OR (95% CI)P-value
Recipient
 Femalea3.05 (1.48–6.30)0.0032.99 (1.33–6.74)0.008
 Age at listing (years)(0.98–1.04)0.526
 Age at transplant (years)1.01 (0.98–1.04)0.534
 Recipient BMIa (kg/m2)1.05 (0.97–1.14)0.232
 HT before 20041.10 (0.50–2.42)0.806
Medical history
 Univentricular physiologya2.39 (1.17–4.86)0.0162.76 (1.23–6.20)0.014
 More than 3 previous surgerya1.78 (0.88–3.58)0.106
 ICD before listing0.79 (0.32–1.95)0.610
 CRT before listing0.76 (0.30–1.97)0.578
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle0.90 (0.45–1.81)0.772
 Previous SVT1.11 (0.55–2.22)0.772
 Haematocrit (%)1.01 (0.97–1.05)0.675
 Haemoglobin (g/dl)1.01 (0.90–1.13)0.926
 Oxygen saturationa (%)0.97 (0.93–1.01)0.101
 Creatinine clearance <60 ml/mina1.99 (0.85–4.67)0.115
 Priority HT listing0.68 (0.31–1.51)0.343
 ECMO/VAD dependent before HT0.73 (0.27–1.99)0.541
 Inotrope dependent before HT0.69 (0.30–1.62)0.398
Donor
 Age (years)1.00 (0.97–1.02)0.897
 BMI (kg/m2)0.99 (0.92–1.07)0.815
 Femalea1.72 (0.85–3.47)0.130
Perioperative data
 Ischaemic time (min)1.00 (1.00-1.01)0.267
VariableUnivariable analysis
Multivariable analysis
OR (95% CI)P-valueAdjusted OR (95% CI)P-value
Recipient
 Femalea3.05 (1.48–6.30)0.0032.99 (1.33–6.74)0.008
 Age at listing (years)(0.98–1.04)0.526
 Age at transplant (years)1.01 (0.98–1.04)0.534
 Recipient BMIa (kg/m2)1.05 (0.97–1.14)0.232
 HT before 20041.10 (0.50–2.42)0.806
Medical history
 Univentricular physiologya2.39 (1.17–4.86)0.0162.76 (1.23–6.20)0.014
 More than 3 previous surgerya1.78 (0.88–3.58)0.106
 ICD before listing0.79 (0.32–1.95)0.610
 CRT before listing0.76 (0.30–1.97)0.578
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle0.90 (0.45–1.81)0.772
 Previous SVT1.11 (0.55–2.22)0.772
 Haematocrit (%)1.01 (0.97–1.05)0.675
 Haemoglobin (g/dl)1.01 (0.90–1.13)0.926
 Oxygen saturationa (%)0.97 (0.93–1.01)0.101
 Creatinine clearance <60 ml/mina1.99 (0.85–4.67)0.115
 Priority HT listing0.68 (0.31–1.51)0.343
 ECMO/VAD dependent before HT0.73 (0.27–1.99)0.541
 Inotrope dependent before HT0.69 (0.30–1.62)0.398
Donor
 Age (years)1.00 (0.97–1.02)0.897
 BMI (kg/m2)0.99 (0.92–1.07)0.815
 Femalea1.72 (0.85–3.47)0.130
Perioperative data
 Ischaemic time (min)1.00 (1.00-1.01)0.267
a

Variables included in a multivariable model.

BMI: body mass index; CI: confidence interval; CRT: cardiac resynchronization therapy; ECMO: extracorporeal membrane oxygenation; HT: heart transplantation; ICD, implantable cardioverter defibrillator; OR: odds ratio; SVT, supraventricular tachycardia; VAD, ventricular assist device.

Table 3:
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Factors associated with early mortality in binary logistic regression analyses

VariableUnivariable analysis
Multivariable analysis
OR (95% CI)P-valueAdjusted OR (95% CI)P-value
Recipient
 Femalea3.05 (1.48–6.30)0.0032.99 (1.33–6.74)0.008
 Age at listing (years)(0.98–1.04)0.526
 Age at transplant (years)1.01 (0.98–1.04)0.534
 Recipient BMIa (kg/m2)1.05 (0.97–1.14)0.232
 HT before 20041.10 (0.50–2.42)0.806
Medical history
 Univentricular physiologya2.39 (1.17–4.86)0.0162.76 (1.23–6.20)0.014
 More than 3 previous surgerya1.78 (0.88–3.58)0.106
 ICD before listing0.79 (0.32–1.95)0.610
 CRT before listing0.76 (0.30–1.97)0.578
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle0.90 (0.45–1.81)0.772
 Previous SVT1.11 (0.55–2.22)0.772
 Haematocrit (%)1.01 (0.97–1.05)0.675
 Haemoglobin (g/dl)1.01 (0.90–1.13)0.926
 Oxygen saturationa (%)0.97 (0.93–1.01)0.101
 Creatinine clearance <60 ml/mina1.99 (0.85–4.67)0.115
 Priority HT listing0.68 (0.31–1.51)0.343
 ECMO/VAD dependent before HT0.73 (0.27–1.99)0.541
 Inotrope dependent before HT0.69 (0.30–1.62)0.398
Donor
 Age (years)1.00 (0.97–1.02)0.897
 BMI (kg/m2)0.99 (0.92–1.07)0.815
 Femalea1.72 (0.85–3.47)0.130
Perioperative data
 Ischaemic time (min)1.00 (1.00-1.01)0.267
VariableUnivariable analysis
Multivariable analysis
OR (95% CI)P-valueAdjusted OR (95% CI)P-value
Recipient
 Femalea3.05 (1.48–6.30)0.0032.99 (1.33–6.74)0.008
 Age at listing (years)(0.98–1.04)0.526
 Age at transplant (years)1.01 (0.98–1.04)0.534
 Recipient BMIa (kg/m2)1.05 (0.97–1.14)0.232
 HT before 20041.10 (0.50–2.42)0.806
Medical history
 Univentricular physiologya2.39 (1.17–4.86)0.0162.76 (1.23–6.20)0.014
 More than 3 previous surgerya1.78 (0.88–3.58)0.106
 ICD before listing0.79 (0.32–1.95)0.610
 CRT before listing0.76 (0.30–1.97)0.578
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventricle0.90 (0.45–1.81)0.772
 Previous SVT1.11 (0.55–2.22)0.772
 Haematocrit (%)1.01 (0.97–1.05)0.675
 Haemoglobin (g/dl)1.01 (0.90–1.13)0.926
 Oxygen saturationa (%)0.97 (0.93–1.01)0.101
 Creatinine clearance <60 ml/mina1.99 (0.85–4.67)0.115
 Priority HT listing0.68 (0.31–1.51)0.343
 ECMO/VAD dependent before HT0.73 (0.27–1.99)0.541
 Inotrope dependent before HT0.69 (0.30–1.62)0.398
Donor
 Age (years)1.00 (0.97–1.02)0.897
 BMI (kg/m2)0.99 (0.92–1.07)0.815
 Femalea1.72 (0.85–3.47)0.130
Perioperative data
 Ischaemic time (min)1.00 (1.00-1.01)0.267
a

Variables included in a multivariable model.

BMI: body mass index; CI: confidence interval; CRT: cardiac resynchronization therapy; ECMO: extracorporeal membrane oxygenation; HT: heart transplantation; ICD, implantable cardioverter defibrillator; OR: odds ratio; SVT, supraventricular tachycardia; VAD, ventricular assist device.

Conditional survival and outcomes

Three patients died after discharge but within the first year and 14 died after the first year. Post-transplant Kaplan–Meier survival curve for the entire cohort is presented in Supplementary Material, Fig. S1. Five patients underwent reHT during the study period, 2 of them died. Nine patients experienced cardiac allograft vasculopathy, and 5 required long-term dialysis. Neoplasia occurred in 8 patients. Among long-term complications, summarized in Table 1, humour rejection occurred more frequently in the univentricular group.

Survival was significantly lower in the univentricular group compared to the biventricular group, P = 0.016 (Fig. 2). The early conditional long-term survival was excellent in both groups without difference between univentricular and biventricular patients (P = 0.764) (Fig. 3).

Post-transplant survival according to cardiac physiology at heart transplantation.
Figure 2:

Post-transplant survival according to cardiac physiology at heart transplantation.

Open in new tabDownload slide
Early conditional survival post-heart transplantation according to cardiac physiology.
Figure 3:

Early conditional survival post-heart transplantation according to cardiac physiology.

Open in new tabDownload slide

Univentricular physiology was not a factor associated with worse conditional survival in the multivariable Cox regression analyses summarized in Table 4. Uni- and multivariable analyses of risk factors associated with overall long-term mortality are listed in Supplementary Material, Table S2.

Table 4:
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Factors associated with conditional survival in multivariable Cox regression

VariableUnivariable analysis
Multivariable analysis
HR (95% CI)P-valueAdjusted HR (95% CI)P-value
Recipient
 Female1.03 (0.33–3.18)0.961
 Age at listing (years)1.01 (0.97–1.06)0.589
 Age at transplant (years)1.01 (0.97 –1.06)0.453
 Recipient BMI (kg/m2)1.02 (0.88–1.17)0.803
 HT after 20040.75 (0.25–2.24)0.606
Medical history
 Univentricular physiologya1.17 (0.43 -3.14)0.7781.24 (0.46–3.36)0.678
 More than 3 previous surgery1.43 (0.54-3.73)0.463
 ICD before listing0.41 (0.05 –3.16)0.392
 CRT before listing2.26 (0.69 –7.42)0.178
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventriclea2.62 (0.86–8.06)0.0922.66 (0.87–8.19)0.088
 Previous SVTa0.54 (0.20–1.47)0.225
 Haematocrit (%)1.01 (0.95–1.07)0.843
 Haemoglobin (g/dl)0.99 (0.83–1.19)0.907
 Oxygen saturationa (%)0.96 (0.91–1.01)0.103
 Creatinine clearance <60 ml/min1.35 (0.38–4.74)0.642
 Priority HT listing1.44 (0.48–4.32)0.514
 ECMO/VAD-dependent before HTa2.51 (0.78–8.08)0.122
 Inotrope-dependent before HTa2.01 (0.67–6.06)0.214
Donor
 Age (years)0.99 (0.95–1.03)0.588
 BMI (kg/m2)1.04 (0.95–1.15)0.404
 Female0.90 (0.33–2.44)0.831
Perioperative data
 Ischaemic time (min)1.00 (0.99–1.01)0.512
VariableUnivariable analysis
Multivariable analysis
HR (95% CI)P-valueAdjusted HR (95% CI)P-value
Recipient
 Female1.03 (0.33–3.18)0.961
 Age at listing (years)1.01 (0.97–1.06)0.589
 Age at transplant (years)1.01 (0.97 –1.06)0.453
 Recipient BMI (kg/m2)1.02 (0.88–1.17)0.803
 HT after 20040.75 (0.25–2.24)0.606
Medical history
 Univentricular physiologya1.17 (0.43 -3.14)0.7781.24 (0.46–3.36)0.678
 More than 3 previous surgery1.43 (0.54-3.73)0.463
 ICD before listing0.41 (0.05 –3.16)0.392
 CRT before listing2.26 (0.69 –7.42)0.178
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventriclea2.62 (0.86–8.06)0.0922.66 (0.87–8.19)0.088
 Previous SVTa0.54 (0.20–1.47)0.225
 Haematocrit (%)1.01 (0.95–1.07)0.843
 Haemoglobin (g/dl)0.99 (0.83–1.19)0.907
 Oxygen saturationa (%)0.96 (0.91–1.01)0.103
 Creatinine clearance <60 ml/min1.35 (0.38–4.74)0.642
 Priority HT listing1.44 (0.48–4.32)0.514
 ECMO/VAD-dependent before HTa2.51 (0.78–8.08)0.122
 Inotrope-dependent before HTa2.01 (0.67–6.06)0.214
Donor
 Age (years)0.99 (0.95–1.03)0.588
 BMI (kg/m2)1.04 (0.95–1.15)0.404
 Female0.90 (0.33–2.44)0.831
Perioperative data
 Ischaemic time (min)1.00 (0.99–1.01)0.512
a

Variables included in a multivariable model.

BMI: body mass index; CI: confidence interval; CRT: cardiac resynchronization therapy; ECMO: extracorporeal membrane oxygenation; HR: hazard ratio; HT: heart transplantation; ICD: implantable cardioverter defibrillator; SVT: supraventricular tachycardia; VAD: ventricular assist device.

Table 4:
Open in new tab

Factors associated with conditional survival in multivariable Cox regression

VariableUnivariable analysis
Multivariable analysis
HR (95% CI)P-valueAdjusted HR (95% CI)P-value
Recipient
 Female1.03 (0.33–3.18)0.961
 Age at listing (years)1.01 (0.97–1.06)0.589
 Age at transplant (years)1.01 (0.97 –1.06)0.453
 Recipient BMI (kg/m2)1.02 (0.88–1.17)0.803
 HT after 20040.75 (0.25–2.24)0.606
Medical history
 Univentricular physiologya1.17 (0.43 -3.14)0.7781.24 (0.46–3.36)0.678
 More than 3 previous surgery1.43 (0.54-3.73)0.463
 ICD before listing0.41 (0.05 –3.16)0.392
 CRT before listing2.26 (0.69 –7.42)0.178
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventriclea2.62 (0.86–8.06)0.0922.66 (0.87–8.19)0.088
 Previous SVTa0.54 (0.20–1.47)0.225
 Haematocrit (%)1.01 (0.95–1.07)0.843
 Haemoglobin (g/dl)0.99 (0.83–1.19)0.907
 Oxygen saturationa (%)0.96 (0.91–1.01)0.103
 Creatinine clearance <60 ml/min1.35 (0.38–4.74)0.642
 Priority HT listing1.44 (0.48–4.32)0.514
 ECMO/VAD-dependent before HTa2.51 (0.78–8.08)0.122
 Inotrope-dependent before HTa2.01 (0.67–6.06)0.214
Donor
 Age (years)0.99 (0.95–1.03)0.588
 BMI (kg/m2)1.04 (0.95–1.15)0.404
 Female0.90 (0.33–2.44)0.831
Perioperative data
 Ischaemic time (min)1.00 (0.99–1.01)0.512
VariableUnivariable analysis
Multivariable analysis
HR (95% CI)P-valueAdjusted HR (95% CI)P-value
Recipient
 Female1.03 (0.33–3.18)0.961
 Age at listing (years)1.01 (0.97–1.06)0.589
 Age at transplant (years)1.01 (0.97 –1.06)0.453
 Recipient BMI (kg/m2)1.02 (0.88–1.17)0.803
 HT after 20040.75 (0.25–2.24)0.606
Medical history
 Univentricular physiologya1.17 (0.43 -3.14)0.7781.24 (0.46–3.36)0.678
 More than 3 previous surgery1.43 (0.54-3.73)0.463
 ICD before listing0.41 (0.05 –3.16)0.392
 CRT before listing2.26 (0.69 –7.42)0.178
Clinical status and laboratory values at transplant
 Clinical signs of right heart ventriclea2.62 (0.86–8.06)0.0922.66 (0.87–8.19)0.088
 Previous SVTa0.54 (0.20–1.47)0.225
 Haematocrit (%)1.01 (0.95–1.07)0.843
 Haemoglobin (g/dl)0.99 (0.83–1.19)0.907
 Oxygen saturationa (%)0.96 (0.91–1.01)0.103
 Creatinine clearance <60 ml/min1.35 (0.38–4.74)0.642
 Priority HT listing1.44 (0.48–4.32)0.514
 ECMO/VAD-dependent before HTa2.51 (0.78–8.08)0.122
 Inotrope-dependent before HTa2.01 (0.67–6.06)0.214
Donor
 Age (years)0.99 (0.95–1.03)0.588
 BMI (kg/m2)1.04 (0.95–1.15)0.404
 Female0.90 (0.33–2.44)0.831
Perioperative data
 Ischaemic time (min)1.00 (0.99–1.01)0.512
a

Variables included in a multivariable model.

BMI: body mass index; CI: confidence interval; CRT: cardiac resynchronization therapy; ECMO: extracorporeal membrane oxygenation; HR: hazard ratio; HT: heart transplantation; ICD: implantable cardioverter defibrillator; SVT: supraventricular tachycardia; VAD: ventricular assist device.

DISCUSSION

In this large French multicentre study of adult patients with CHD who underwent HT, we observed an overall mortality of 42.7% at 10 years with better early survival for biventricular patients. We found that univentricular physiology and female recipient gender were associated with early in the multivariable analysis. However, the early conditional long-term survival was excellent in both groups, without difference in multivariate analysis.

Overall mortality related to HT in ACHD patients is a concern [10], especially early mortality recognized as the Achilles heel of transplantation in ACHD [16]. Indeed, a third of patients died the year following HT. Reasons for this high death rate are probably multifactorial, including the anatomical complexity inherent in CHD and anomalies of the pulmonary vascular bed. The time of cold graft ischaemia remains a debated risk factor of long-term mortality [17], in our cohort no association was found in univariate and multivariable analysis for early and long-term survival. Consistent with prior studies, graft dysfunction was the main cause of death [18]. However, interestingly, as shown in Fig. 3, conditional survival was excellent in both groups, with only 5 patients in the univentricular group and 9 patients in the biventricular group died during 20 years of follow-up. Several studies demonstrated in a long-term analysis study, that ACHD patients had better 1-year conditional long-term survival post-HT compared to non-ACHD patients [18].

The impact of univentricular physiology on mortality was, until now, uncertain in the literature. Two articles did not find any association [19, 20], whereas 3 others did [21–23]. However, methodological limitations preclude definitive conclusions. For example, 2 studies were not restricted to ACHD patients [20, 21], another was limited in power [19]. To our knowledge, this is the first study to find an independent association between univentricular physiology and higher risk of early mortality with detailed clinical and biological perioperative data for ACHD patients. To date, the underlying reasons are not completely understood and remain speculative. Biological disorders related to low oxygen saturation, such as polycythaemia, predispose to coagulation disorders aggravated by blood transfusions recognized as a risk factor for primary graft dysfunction and increased morbidity [24]. The high number of prior HT surgeries may also explain the higher number of femoral cannulation prior to the initiation of CPB to avoid damage related to reoperation in patients multioperated [25, 26]. The univentricular group required concomitant procedure during HT, especially on the great vessels but also on the PA branches, which could explain the prolongation of CPB time, aortic clamping and cold ischaemia of the graft, known as factors of mortality [21, 27, 28], primary graft dysfunction [24] and postoperative coagulopathy [22]. In addition, atrial arrhythmias, more important in the univentricular group, are a well-recognized factor of morbidity and mortality in CHD patients [29], especially in Fontan population [30].

Our multivariable analysis identified female recipient gender as independently associated with higher early mortality. Few studies have identified female recipient gender as a risk factor for early and late morality in paediatric population [31] and the 2004 International Society for Heart and Lung Transplantation report even identified female gender as a protective factor in the adult non-ACHD population [17]. The reason remains unclear but is likely multifactorial and may include immunologic, genetic, hormonal, and/or psycho-social causes.

The early mortality after HT in ACHD patients is an important issue that needs to be addressed, as the number of candidates for HT will continue to increase with the increased life expectancy of CHD patients, exacerbating the severe lack of grafts already prevalent today. The future challenges to improve the morbidity and mortality of ACHD patients at HT are therefore the best timing for listing patients in order to avoid any systemic complications. The optimal timing of HT remains a hot topic, especially in the univentricular population. Although not identified in our multivariable analysis, it seems essential to minimize cold ischaemia time by the management by cardiologists, surgeons and intensivists dedicated for CHD [32]. Finally, it seems interesting to elucidate the role of female gender as a risk factor of death.

Limitations

Our study has some limitations including all of those that apply to any retrospective study. Pre-transplant data for old-era patients were inconsistently available such as panel reactive antibody, peak oxygen consumption or preoperative pulmonary vascular resistance. Data on combined transplantation were not evaluated in this study. The long inclusion period is an issue in the interpretation of these results as the standard of care and patients’ profile has changed. The ejection fraction was not available or reliable for all the univentricular patients, especially for the oldest era. Our study was not designed to assess predictors of outcomes in the specific group of univentricular patients but will be the subject of another study.

CONCLUSION

ACHD recipients have a high incidence of overall mortality due to a high rate of early mortality. Univentricular physiology was associated with a significantly increased risk of early death compared to biventricular physiology. Once out of the initial post-operative period, late mortality was no longer different between the 2 physiologies. After an early high-risk period, the long-term survival was excellent for both groups. Further studies to assess risk factors for death and complications in univentricular patients are essential to determining appropriate candidates and the most appropriate timing for transplantation.

Presented at the 36th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Milan, Italy, 4–8 October 2022.

SUPPLEMENTARY MATERIAL

Supplementary material is available at EJCTS online.

ACKNOWLEDGEMENTS

The authors thank Fatima-Zohra Bouzina (Department of Cardio-Vascular Surgery, European George Pompidou Hospital) and Pascale Weber (Cardio-Thoracic Surgery Unit and Pathology Department, La Pitié-Salpétrière Hospital).

FUNDING

Nabil Dib is supported by the French Federation of Cardiology (FFC) and ADETEC grants.

Conflict of interest: none declared.

DATA AVAILABILITY

All relevant data are within the manuscript and its Supporting Information files.

Author contributions

Nabil Dib: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Validation; Writing—original draft. Laurence Iserin: Writing—review & editing. Shaida Varnous: Writing—review & editing. Romain Guillemain: Writing—review & editing. Sebastien Hascoet: Writing—review & editing. Emre Belli: Writing—review & editing. Sarah Cohen: Supervision; Validation; Writing—review & editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Sandeep Sainathan and the other anonymous reviewer(s) for their contribution to the peer review process of this article.

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ABBREVIATIONS

    ABBREVIATIONS
     
  • ACHD

    Adult congenital heart disease

    •  
  • CHD

    Congenital heart disease

    •  
  • CI

    Confidence interval

    •  
  • CPB

    Cardiopulmonary bypass

    •  
  • HF

    Heart failure

    •  
  • HT

    Heart transplantation

    •  
  • PA

    Pulmonary artery

    •  
  • VA-ECMO

    Venoarterial extracorporeal membrane oxygenation

© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/pages/standard-publication-reuse-rights)
Topic:
Subject
Fontan Operation Grown-up Congenital Heart Disease Heart Failure Surgery (Congenital) Univentricular Palliation
Issue Section:
CONGENITAL
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