Pediatric heart transplantation in infants and small children under 3 years of age: Single center experience – “Early and long-term results”
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.
Section snippets
Study population and study design
In our patients collective were not performed any combined transplantation (heart- and kidney transplantation or heart- and liver transplantation). Heart- and lung-transplantations analysis were studied in a separate report (in processing), and ABO incompatible heart transplantations were also analyzed in separate study (in processing). Because of several different immunosuppression regimen, patients after heart- and lung-transplantation and after ABO incompatible heart transplantation were
Results
See in Table 2, Figs. 1a, 2b.
The median (IQR) follow-up time was 13.2 years (5.7–19.5).
Median age (years) of patients at time to HTx was 0.9 (0.25–2.05). 52% of them were male. Median body weight (kg) was 6.8 (4.3–10.0), median BMI (kg/m2) was 14.2 (12.3–15.7). In 37% (n = 17) of patients was CHF the indication to HTx, in 33% (n = 15) of them occurred a single ventricular physiology. All patients were in end-stage heart failure.
Concomitant surgical repairs were required in 17 (37%) cases (e.g.
Discussion
Heart transplantation in infants and young children remains one of the special challenges in pediatric cardiac surgery. At first, children with CHD usually have one or more previous heart palliations/repairs and at second, fewer suitable donors are available, which means that patients spend longer time on the waiting list and many of them require more VAD support prior to transplantation.
When retransplantation was performed in setting of early graft failure, the results were quite poor [18], we
Conclusion
In conclusion, pediatric heart transplantation is still the best therapeutic option in infants and children in end-stage cardiac failure. Long-term survival are acceptable and comparable to international results. Early and late graft failure as reason to death was high, as reason to retransplantation acceptable and comparable to international results. The history of TVP influenced graft failure. The number of patients with HLHS (with prior HTx or Norwood failure) as indication to pHTx has
Financial support
No grants used, the funding is by hospital funding only
Authors statement
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. All authors had full control of the design of the study, methods used, and outcome parameters, analysis of data and production of the written report.
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.
Declaration of Competing Interest
There is no conflict of interest by any of the authors regarding this report.
Acknowledgments
We would like to express our gratitude to cardiac surgeon Prof. Bruno Reichart and pediatric cardiologist Prof. Heinrich Netz for their role in advancing pediatric heart transplantation at our institution.
We would also like to thank Dr. Linda Zimmerling for improving the study data from October 1988 to October 2015 as part of her doctoral thesis (D.M.).
We thank Alexander Crispin (Institute for Medical Information Processing, Biometry and Epidemiology; IBE) of the Ludwig-Maximilians-University,
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