Pediatric heart transplantation in infants and small children under 3 years of age: Single center experience – “Early and long-term results”

Highlights

• First because, patients with congenital heart disease in end-stage heart failure have already undergone one or more previous heart operations.

• Second, because of shortage suitable donors many patients need mechanically assist device support as bridge to transplantation.

• Heart transplantation in infants and young children remains one of the majority challenges in pediatric cardiac surgery.

• Our goal was to identify serious adverse events associated with mortality and graft failure after pediatric heart transplantation.

Abstract

Objectives

We analyzed the early and long-term survival after ABO-compatible heart transplantation in children under 3 years of age from 1991 to 2021 at our center. This retrospective and descriptive study aimed to identify serious adverse events associated with mortality after pediatric heart transplantation.

Patients and methods

46 patients with congenital heart failure (37%) in end-stage heart failure have undergone a pediatric heart transplantation. Primary outcome of interest was survival at follow-up time.

Results

Median (IQR) follow-up time (y), age (y), body-weight (kg) and BMI (kg/cm²) were 13.2 (5.7–19.5), 0.9 (0.2–2.0), 6.8 (4.3–10.0) and 14.2 (12.3–15.7). Twenty-four (52%) patients were male. 15 patients (33%) had a single ventricle physiology. At 30- days survival rate was 94 ± 4%. Survival rate at 1, 5, 10 and 15 years post HTx was 87 ± 5%, 84 ± 6%, 79 ± 6% and 63 ± 8%. One child underwent re-transplantation after 4 years, and another one after 11 years – in both cases due to graft failure. Higher early mortality in patients under 3 months of age and in patients with single ventricle physiology. Transplant free survival at 15 years was in children with cardiomyopathy better (71 ± 10%) than in those with congenital heart disease (50 ± 13%). One or more previous heart surgeries prior to HTx (n = 21) were associated to more mortality.

Conclusion

Pediatric heart transplantation has acceptable long-term results and is still the best therapeutic option in children with end-stage cardiac failure. Underlying anomalies and single ventricle physiology, age below 3 months had a significant impact on survival.

Introduction

The first pediatric heart transplantation was performed in an infant under 3 months of age at time to transplantation in September 1991 at our center.

With the advent of better immunosuppressive therapy, which began with the introduction of cyclosporine A in 1981, the first successful HTx was performed in Germany in 1983 in Munich. From then on, HTx was the only treatment approved in patients with severe heart failure, with good long-term results [9,11].

Forty- six pediatric patients after heart transplantation were analyzed. Primary outcome of interest was survival at follow-up time. Secondary outcome was early and late graft failure. We report the impact of donor/recipient mismatch for gender, BMI, CMV-IgG, and EBV-IgG; main indication; single ventricle physiology, previous heart procedure, pre- HTx ECLS/ECMO and pre-pHTx VAD support on early and long-term outcomes.

Ethical approval statement: The study followed the ethical standards of the Declaration of Helsinki and was approved by the institutional review board of the Ludwig Maximilians University of Munich.

Definitions:

Early survival outcomes were assessed at 30- days post transplant and long-term survival was determined at the last follow- up time.

Histopathological classification of cellular rejection reaction was defined as by ISHLT – classification. Rejection reaction was diagnosed in echocardiography with decreasing of diastolic LV function or in catheterization with biopsy and histology.

Early graft failure was described as rejection reaction with diastolic graft dysfunction in the first 90 days after HTx or necessity of permanent cardiac pacing. Late graft failure was demarked first in existing diastolic graft dysfunction in long-term after 90 days post-transplant with rejection reactions, and then in development of transplant vasculopathy, or ongoing cardiac arrhythmia with requiring pacemaker implantation.

BMI mismatch was defined in cases of 0.8 > donor/ recipient >1.2.

Gender mismatch in donor / recipient was marked in m/f or in f/m.

CMV- IgG or EBV- IgG of donor / recipient were termed as positive/ negative or negative/ positive.

Renal dysfunction was demarked as creatinine level > o.3–1.4 mg/dl (according to age), or urea level > 36 mg/dl and creatinine clearance <80–90 ml/min x 1.73 m². Oliguria and anuria with high level of creatinine and creatinine clearance and necessity of long-term dialysis after transplantation was defined as renal failure.

Statistics: Data were analyzed using SPSS Statistics 27 software (IBM®). Continuous variables were expressed as median (IQR) and categorical variables were expressed as frequencies with percentages (%). Differences between means were confirmed using the Chi-squared exam. Statistical significance was set at p < 0.050. Cumulative survival curves were constructed using the Kaplan-Meier method. A log-rank test was performed to compare survival between the groups expending a hazard ratio (HR) by univariable Cox regression analysis. We used one-way analysis of variance (one-way ANOVA), the Chi-squared and Fischer's exact test to analyze perioperative factors and technical methods to determine the effect of postoperative results with a statistical significance level 95.0% between the conditions and p < 0.05.