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Tricuspid annular plane systolic excursion (TAPSE) is important in the noninvasive echocardiographic assessment of right heart function. This retrospective observational study shows correlations of TAPSE with invasive right heart catheterization parameters after pediatric heart transplantation (HTx). The study included patients after pediatric HTx with cardiac catheterizations in 2018/2019 and measurement of TAPSE (n = 52 patients with 57 examinations; 50.9% adults, 52.6% female, median age: 18.54 years). TAPSE was compared with normal values. Stepwise, linear and multiple regression were used to show influencing variables on TAPSE. Mean TAPSE z-score was -3.48 (SD: 2.25) and 68.4% of HTx-recipients showed abnormally reduced TAPSE (z-score ←2) compared to normal values. Multiple regression (p-value <0.001; corrected R 2 = 0.338) showed significant correlations of time since HTx (p-value <0.001) and mPAP (p-value: 0.008) with TAPSE z-scores. Divided into subgroups (time since HTx <10 and ≥10 years), TAPSE and mPAP correlated only ≥10 years after HTx (p-value = 0.002). This study provides data of TAPSE even ≥10 years after pediatric HTx. Most patients showed a decreased TAPSE early after HTx, which improved over time. TAPSE z-scores correlated significantly with time since HTx and mPAP, especially ≥10 years post-HTx. Therefore, TAPSE must be used carefully in the early follow-up., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Cardiac allograft vasculopathy (CAV) and nephrotoxicity affect long-term survival after heart transplantation (HTX). Studies, mostly conducted in adults, showed a positive effect of everolimus (EVL) on these problems. We describe the effects of conversion of the immunosuppressive therapy to an everolimus including regime on CAV, renal function, and safety in heart transplanted children/adolescents., Methods: This retrospective single-center study included 36 participants (mean time after HTX 6.3 ± 4.7 years). Descriptive pre/post-comparisons were performed with an observation period partially up to 4 years. Impact on CAV was assessed based on intravascular imaging and Stanford grading. Safety analysis included cytomegalovirus (CMV)-infection and acute rejection., Results: In terms of CAV (9 out of 36 patients) four showed no progression, three an improvement, one a worsening; one new diagnosis. The average CrCl showed a significant improvement 6, 12, and 24 months after conversion regarding all patients (n = 29). There was no acute rejection or CMV-infection., Conclusion: Conversion to an EVL-based therapy after pediatric HTX is a safe immunosuppressive regime without increasing risk of acute rejection or CMV-infection. There was some evidence of reduction in progression of CAV and a significant improvement of the renal function., (© 2020 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Objective: The aim of the current study is to measure long-term executive function, motor outcome, and QoL in children, adolescents, and young adults after VAD and Htx., Methods: Patients were examined during routine follow-up. Investigation tools were used as follows: Examination for MND of motor outcomes, Epitrack ® for attention and executive functioning, and Kidscreen-52 and EQ-5D-5L questionnaires for QoL. Additional data were retrospectively obtained by an analysis of patient medical records., Results: Out of 145 heart transplant recipients at the department of pediatric cardiology of the University Hospital Munich, 39 were implanted with a VAD between 1992 and 2016. Seventeen (43.6%) patients died before or after Htx; 22 (56.4%) patients were included in our study. Mean age at transplant was 9.52 years (range: 0.58-24.39 years, median 9), and the mean follow-up time after Htx was 6.18 years (range: 0.05-14.60 years, median 5.82). MND examination could be performed in 13 patients (normal MND: n = 11, simple MND: n = 1, complex MND: n = 1). Executive functioning was tested in 15 patients. Two (13.3%) patients had good results, six (40%) average results, three (20%) borderline results, and four (26.7%) impaired results. QoL (Kidscreen n = 7, EQ-5D-5L n = 8) was similar to a healthy German population., Conclusion: Motor outcome, executive functioning and QoL in survivors of VAD bridging therapy and Htx can be good, though underlying diseases and therapies are associated with a high risk of cerebral ischemic or hemorrhagic complications., (© 2019 The Authors. Pediatric Transplantation published by Wiley Periodicals, Inc.)

Arterial hypertension complicates the follow-up of heart- and heart/lung-transplanted children. We investigated the evolution of BRS as short-time BP regulation mechanism and BP after heart and heart/lung transplantation. Twenty patients (15 males; mean age 15.1 ± 4.3 yr) were studied twice at intervals of 2.96 ± 0.87 yr. BRS was calculated using non-invasive beat-to-beat BP measurement system. HRV was calculated (LF, sympathetic influence; HF, parasympathetic influence). BRS increased in 10 patients (3.67 ± 1.43 ms/mmHg vs. 7.59 ± 3.40 mmHg, p = 0.005) (group 1). Six of 10 patients received antihypertensive medication. BRS decreased or remained unchanged in 10 patients (8.93 ± 7.9 ms/mmHg vs. 5.32 ± 6.6 ms/mmHg, p = 0.008) (group 2) with 9/10 patients necessitating antihypertensive medication. Group 1 showed LF/HF increase (LF/HF 1.03 ± 0.9 vs. 4.36 ± 2.32, p = 0.03); group 2 showed LF/HF decrease (LF/HF 3.7 ± 2.1 vs. 1.84 ± 1.1, p = 0.023). Evolution of BRS after heart and heart/lung transplantation in childhood seems to influence the necessity of antihypertensive medication. With time, increasing short-time BP regulation involving sympathetic reinnervation may improve BP., (© 2011 John Wiley & Sons A/S.)

Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p < 0.001), with more patients having protective antibody levels against diphtheria (p < 0.02) and tetanus (p < 0.001). There was no increased proliferation in non-stimulated or stimulated cultures after vaccination. The number of T-lymphocytes activated by the vaccination antigens was similar pre- and post-vaccination, whereas HLA-DR-expression on stimulated and non-stimulated CD4(+) T-cells increased significantly. Increase in antibodies was negatively correlated with tacrolimus dose, and impaired cellular immunity was associated with higher tacrolimus dose and steroid use. Adverse events were similar to the general population; serious adverse events and rejection did not occur. Vaccination with inactivated vaccines can be performed safely in immunosuppressed children after thoracic transplantation and induces protective antibody levels in the majority of patients. Impaired induction of specific cellular immunity is correlated with intensity of immunosuppression and may explain reduced sustainability of antibodies., (© 2011 John Wiley & Sons A/S.)

Context: Cardiovascular disease caused by atherosclerosis is a major cause of morbidity and mortality in adult diabetic patients. In children, we detected signs of subclinical atherosclerosis in a large patient cohort. This study reports the results of a longitudinal observation in this patient group., Patients and Methods: Of the 37/150 diabetic children in whom an increased intima-media thickness (IMT) of the carotid artery had been found, 27 (mean age 14.6 +/- 2.6 yrs) could be reevaluated 2 yrs after the initial study. Of the 27, 5 patients were on medication with angiotensin-converting enzyme (ACE) inhibitors, and all patients underwent detailed counselling of their lifestyle, sports activity, and nutritional habits., Results: Mean IMT increased significantly (0.49 +/- 0.02 mm vs. 0.51 +/- 0.026 mm, p < 0.05) However, there was no significant change compared to normal values (mean IMT z-score 2.4 +/- 0.3 vs. 2.6 +/- 0.5). Of the 27, 13 patients (48%) showed a progression of the IMT whereas in 14/27 patients the IMT values remained stable. In these subgroups, patients with IMT progression showed a higher hemoglobin A1c (HbA1c) (7.5 +/- 0.8 vs. 7.1 +/- 0.7, p < 0.05) and a slightly higher systolic blood pressure (120 +/- 14.4 vs. 113.9 +/- 12.1, p = 0.08)., Conclusions: In a well-selected group of diabetic children, mean IMT progression during a 2-yr period did not exceed the physiological increase. Children with a higher HbA1c and a higher systolic blood pressure showed a progression of the IMT. Control of atherogenic risk factors in diabetic children may help to avoid subclinical atherosclerosis progression.

In the first two yr of life blood-group incompatible (ABO-incompatible) heart transplantation can be performed leading to immune tolerance to donor blood group. Antibody titers should be below 1:4. VAD use is correlated with sensitization toward blood-group antigens. A boy was diagnosed with dilated cardiomyopathy at nine months of age and listed for 0-compatible transplantation. Progressive heart failure required implantation of a left VAD. His listing was extended for ABO-incompatible transplantation despite antibody titers of 1:32 anti-A and 1:8 anti-B. After 26 days on VAD, he was transplanted with a B donor heart. No hyperacute or acute rejection occurred in 12 months post-transplant. Anti-B antibodies rose to a maximum of 1:2. No use of rituximab or plasmapheresis was required. There are no signs of graft vasculopathy. This indicates that inclusion criteria for ABO-incompatible transplantation may be extended to immediate cases. This is the first case with a healthy immune system to show signs of tolerance development after ABO-incompatible heart transplantation with increased prior antibody titers and without specific treatment.

Children after heart transplantation are considered as at-risk patients for extracardiac atherosclerotic complications. Noninvasive ultrasound measurement of the common carotid artery (IMT) provides valid information about the endothelial structure of the vascular system. Twenty-two patients (17 male, mean age 12.4 +/- 4.5 yr) after heart and (5.7 +/- 4.5 yr) heart-lung transplantation were enrolled. The mean IMT was measured and compared with a control group (18 children, 10 male, mean age 11.8 +/- 1.8 yr) and to normative data. Transplanted children had a higher IMT than controls (0.453 +/- 0.003 vs. 0.424 +/- 0.002 mm, p < 0.001). IMT-SDS was increased as well (1.6 +/- 0.1 vs. 0.8 +/- 0, p < 0.001). Transplanted children had a higher LDL/HDL-ratio (2.2 +/- 0.2 vs. 1.2 +/- 0.1, p < 0.001). Time after transplantation, age at the time of transplantation, or medical therapy did not influence the findings. We found evidence for subclinical atherosclerosis in children after heart and heart-lung transplantation. Even if single atherosclerotic risk factors could not be identified, transplanted children seem to be at risk for atherosclerosis. Our findings support the recently published statement of the AHA-Expert panel: after heart transplantation atherosclerotic complications may occur with increased incidence. We propose the IMT-measurement in these patients as an easy method to assess the vascular status and to guide preventive measures.

Introduction: Heart rate variability (HRV) is reduced in adults and children after cardiac transplantation. Testing of HRV has been used to assess re-innervation of the cardiac graft; its reliability in ruling out acute graft rejection is still under investigation. This study used a short-term test on HRV in 23 heart and heart-lung transplanted children and adolescents and compared the results with 24-h ECG recordings., Patients and Methods: Twenty-three subjects (16.3+/-4.2 yr; 10 females) underwent a 10-min HRV test at two occasions and one 24-h ECG. HRV was calculated according to the time domain method (RR interval, standard deviation of RR interval) and the frequency domain method (total power, LF and HF for assessment of sympathovagal modulation of heart rate)., Results: Correlation between the short-term tests and 24-h ECG was high with regard to the frequency domain analysis of HRV. Correlation was less pronounced in the time domain method., Conclusions: In heart and heart-lung-transplanted children and adolescents, due to reduced overall HRV short-term testing may give as reliable data as 24-h ECG. Therefore, especially when power spectral analysis has to be performed as a longitudinal assessment of re-innervation of the cardiac graft, short-term testing may offer an easily applicable and non-invasive diagnostic tool. Further studies are warranted to investigate whether HRV testing may contribute to rule out acute graft rejection.