Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

AIM: Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. METHODS: In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. RESULTS: In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. CONCLUSION: While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

German Registry for Cardiac Operations and Interventions in Congenital Heart Disease: Annual Report 2022.

BACKGROUND: The German Registry for Cardiac Operations and Interventions in Patients with Congenital Heart Disease is a voluntary registry initiated by the German Society for Thoracic and Cardiovascular Surgery and the German Society for Pediatric Cardiology and Congenital Heart Defects. Since 2012, the registry collects data for the assessment of treatment and outcomes of surgical and interventional procedures in patients with congenital heart disease (CHD) of all age groups. METHODS: This real-world, prospective all-comers registry collects clinical and procedural characteristics, adverse events (AEs), mortality, and medium-term outcomes (up to 90 days) of patients undergoing surgical and interventional. A unique pseudonymous personal identifier (PID) allows longitudinal data acquisition in case of further invasive treatment in any participating German heart center. Prior to evaluation, all data sets are monitored for data completeness and integrity. Evaluation includes risk stratification of interventional and surgical procedures and classification of AEs. Each year's data are summarized in annual reports containing detailed information on the entire cohort, all subgroups, and 15 index procedures. In addition, each participating center receives an institutional benchmark report for comparison with the national results. This paper presents a comprehensive summary of the annual report 2021. RESULTS: In 2021, a total of 5,439 patients were included by 22 participating centers. In total, 3,721 surgical, 3,413 interventional, and 34 hybrid procedures were performed during 6,122 hospital stays. 2,220 cases (36.3%) could be allocated to the 15 index procedures. The mean unadjusted in-hospital mortality ranged from 0.4% among interventional and 2% among surgical cases up to 6.2 % in cases with multiple procedures. In-hospital mortality among index procedures accounted for 2.3% in total cavopulmonary connection, 20.3% in Norwood procedures, and 0.4% following interventional closure of patent ductus arteriosus. For the remaining seven surgical and five interventional index procedures, no in-hospital deaths were recorded. The 10-year longitudinal evaluation of 1,795 patients after tetralogy of Fallot repair revealed repeat interventional or surgical procedures in 21% of the patients. Over the same period, 31.1% of 2,037 patients, following initial treatment of native coarctation, required at least one additional hospital admission, 39.4% after initial interventional, and 21.3% after initial surgical therapy. CONCLUSION: The annual report 2021 of the German Registry for Cardiac Operations and Interventions in CHD shows continuously good results in accordance with previous data of the registry. Compared to international registries on CHD, it can be ascertained that in Germany invasive treatment of CHD is offered on a high medical level with excellent quality. The proven fact that patients with various malformations like tetralogy of Fallot and coarctation of the aorta require repeat procedures during follow-up confirms the urgent requirement for longitudinal assessment of all patients presenting with complex lesions.

Outcomes of transcatheter pulmonary SAPIEN 3 valve implantation: an international registry.

BACKGROUND AND AIMS: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI. METHODS: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries. RESULTS: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively. CONCLUSIONS: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.

Case report: Beneficial long-term effect of the atrial-flow-regulator device in a pediatric patient with idiopathic pulmonary arterial hypertension and recurring syncope.

We report the long-term effect after successfully implanting an 8 mm Atrial-flow-regulator (AFR) device in a 7-year-old girl with idiopathic pulmonary hypertension with persistent syncope under triple therapy with significant improvement after implantation and absence of any further syncope. Early Implantation of the AFR device (Occlutech, Germany) can be efficient and safe interventional therapy option for pulmonary arterial hypertension with a history of syncope.

Evaluation of the diagnostic and prognostic potential of optical coherence tomography (OCT) of the pulmonary arteries during standardised right heart catheterisation in patients with pulmonary hypertension: a cross-sectional single-centre experience.

Background: Pulmonary hypertension (PH) is diagnosed based on an invasive evaluation of the mean pulmonary artery (PA) pressure. The morphological assessment of the pulmonary arteries was only recently not feasible. With the advent of optical coherence tomography (OCT)-imaging, an accessible tool allows to study PA morphology longitudinally. The primary hypothesis was that OCT distincts the PA structure of PH patients from control subjects. The secondary hypothesis was that PA wall thickness (WT) correlates with the progression of PH. Methods: This is a retrospective monocentric study of 28 paediatric patients with (PH group) and without PH (control group) who had undergone cardiac catheterisation including OCT imaging of the PA branches. OCT parameters analysed were WT and the quotient of WT and diameter (WT/DM) and those were compared between the PH group and the control group. In addition, the OCT parameters were aligned with the haemodynamic parameters to evaluate the potential of OCT as a risk factor for patients with PH. Results: WT and WT/DM in the PH group were significantly higher compared to the control group {WT: 0.150 [0.230, range (R): 0.100-0.330] vs. 0.100 [0.050, R: 0.080-0.130] mm, P<0.001; WT/DM: 0.06 [0.05] vs. 0.03 [0.01], P=0.006}. There were highly significant correlations between WT and WT/DM with the haemodynamic parameters mean pulmonary arterial pressure (mPAP) [Spearman correlation coefficient (rs) =0.702, P<0.001; rs=0.621, P<0.001], systolic pulmonary arterial pressure (sPAP) (rs=0.668, P<0.001; rs=0.658, P<0.001) and WT and pulmonary vascular resistance (PVR) (rs=0.590, P=0.02). Also, there was a significant correlation between WT and WT/DM and the risk factors quotient of mPAP and mean systemic arterial pressure (mSAP) (mPAP/mSAP) (rs=0.686, P<0.001; rs=0.644, P<0.001) and pulmonary vascular resistance index (PVRI) (rs=0.758, P=0.002; rs=0.594, P=0.02). Conclusions: OCT can detect significant differences in WT of the PA in patients with PH. Furthermore, the OCT parameters correlate significantly with haemodynamic parameters and risk factors for patients with PH. More investigations are required to evaluate to what extent the impact of OCT can contribute to the clinical care of children with PH.

Oscillometric pulse wave velocity estimated via the Mobil-O-Graph shows excellent accuracy in children, adolescents and young adults: an invasive validation study.

AIMS: Increased arterial stiffness, measured as arterial pulse wave velocity (PWV) is associated with an elevated cardiovascular risk. Although noninvasive PWV measurement methods have been validated by invasive measurement, there is little such data on pediatric patients. The purpose of this study was to 'fill the gap' by validating PWV obtained by Mobil-O-Graph in children, adolescents in comparison to young adults. METHODS: Sixty patients (25 male, mean age 16.6 years; range 3-35 years) were included in this study. Fifty-one patients underwent cardiac catheterization after a heart transplantation (HTX) and nine for interventional atrial septal defect-closure. Specific invasive pulse wave velocities were assessed for the ascending aorta (aPWV) and entire central aorta (cPWV). These invasive PWV results were compared to simultaneously measured brachial cuff readings using Mobil-O-Graph (oPWV) stratified by age in two groups (PEDIATRICS <18 years|ADULTS ≥18 years). RESULTS: Correlation analysis showed a positive linear relation between both invasive PWV measurements and the oPWV in all ages (cPWV/oPWV: r  = 0.417, aPWV/oPWV: r  = 0.628; P  < 0.001). The oPWV data agreed better with the aPWV in mean-value comparisons and correlations with mean difference in PEDIATRICS was 0.41 ±â€Š0.41 m/s (95% confidence interval 0.27-0.55). We also found the cPWV to be faster than the aPWV particularly in adults. In addition, cPWV correlated closer with age ( r  = 0.393, P  < 0.05). CONCLUSION: Estimated oPWV using the Mobil-O-Graph demonstrated excellent accuracy in adults and pediatric patients. Therefore, the Mobil-O-Graph can be implemented as an ambulatory PWV measuring tool for pediatric cardiovascular risk stratification. CLINICAL TRIAL REGISTRATION: German clinical trial registration, DRKS00015066.

German Registry for Cardiac Operations and Interventions in Patients with Congenital Heart Disease: Report 2021 and 9 Years' Longitudinal Observations on Fallot and Coarctation Patients.

BACKGROUND: The annual report of the German Quality Assurance of Congenital Heart Disease displays a broad overview on outcome of interventional and surgical treatment with respect to patient's age and risk categorization. Particular features of the German all-comers registry are the inclusion of all interventional and surgical procedures, the possibility to record repeated treatments with distinct individual patient assignment, and to record various procedures within one case. METHODS: International Pediatric and Congenital Cardiac Code terminology for diagnoses and procedures as well as classified adverse events, also recording of demographic data, key procedural performance indicators, and key quality indicators (mortality, adverse event rates). Surgical and interventional adverse events were classified according to the Society of Thoracic Surgeons and to the Congenital Heart Disease Adjustment for Risk Method of the congenital cardiac catheterization project on outcomes. Annual analysis of all cases and additional long-term evaluation of patients after repair of Fallot and primary treatment of native coarctation of the aorta were performed. RESULTS: In 2020, 5,532 patients with 6,051 cases (hospital stays) with 6,986 procedures were treated in 23 German institutions. Cases dispense on 618 newborns (10.2%), 1,532 infants (25.3%), 3,077 children (50.9%), and 824 adults (13.6%). Freedom from adverse events was 94.5% in 2,795 interventional cases, 67.9% in 2,887 surgical cases, and 42.9% in 336 cases with multiple procedures (without considering the 33 hybrid interventions). In-hospital mortality was 0.5% in interventional, 1.6% in surgical, and 5.7% in cases with multiple treatments. Long-term observation of 1,632 patient after repair of Fallot depicts the impact of previous palliation in 18% of the patients on the rate of 20.8% redo cases. Differentiated analysis of 1,864 patients with native coarctation picture clear differences of patient, age, and procedure selection and outcome. The overall redo procedure rate in this patient population is high with 30.8%. CONCLUSION: Improvement in quality of care requires detailed analysis of risks, performance indicators, and outcomes. The high necessity of redo procedures in patients with complex congenital heart disease underlines the imperative need of long-term observations.

3D-printed heart models for hands-on training in pediatric cardiology - the future of modern learning and teaching?

Background: This project aims to develop a new concept in training pediatric cardiologists to meet the requirements of interventional cardiac catheterizations today in terms of complexity and importance. This newly developed hands-on training program is supposed to enable the acquisition of certain skills which are necessary when investigating and treating patients in a catheter laboratory. Methods: Based on anonymous CT-scans of pediatric patients' digital 3D heart models with or without cardiac defects were developed and printed three-dimensionally in a flexible material visible under X-ray. Hands-on training courses were offered using models of a healthy heart and the most common congenital heart defects (CHD). An evaluation was performed by quantifying fluoroscopy times (FL-time) and a questionnaire. Results: The acceptance of theoretical and practical contents within the hands-on training was very positive. It was demonstrated that it is possible to master various steps of a diagnostic procedure and an intervention as well as to practice and repeat them independently which significantly reduced FL-time. The participants stated that the hands-on training led to more confidence in interventions on real patients. Conclusion: With the development of a training module using 3D-printed heart models, basic and advanced training in the field of diagnostic cardiac examinations as well as interventional therapies of CHD is possible. The learning effect for both, practical skills and theoretical understanding, was significant which underlines the importance of integrating such hands-on trainings on 3D heart models in education and practical training.

Assessment of sex- and age-dependency of risk factors for intimal hyperplasia in heart transplant patients using the high resolution of optical coherence tomography.

BACKGROUND: Intimal hyperplasia in cardiac allograft vasculopathy (CAVIH) is limiting survival in pediatric and adult patients after heart transplantation (HTx). Analysis of risk factors for CAVIH using the high resolution of intracoronary optical coherence tomography (OCT) is scarce, particularly in children, and recommendations for CAV prevention are largely based on data obtained in adults. Whether the predictive value of risk factors is age- or sex-dependent is unknown. METHODS AND RESULTS: We used OCT to test the age- and sex-dependency of established risk factors regarding pathological CAVIH in a cohort of 102 pediatric and adult HTx patients (35% <18 years, 69% male). Modifiable parameters such as lipid values, and the diagnoses of dyslipidemia and diabetes showed age- and sex-dependent differences. Regarding CAVIH, receiver-operating characteristic analysis showed that LDL-c was relevant only in female patients (area under the curve [AUC] 0.79, p = 0.007), and total cholesterol in female (AUC 0.81; p = 0.004) and pediatric patients (AUC 0.73, p < 0.05). The association of dyslipidemia with CAVIH was stronger in adult (odds ratio [OR] 6.33) than in pediatric patients (OR 5.00) and in women (OR 6.00) than in men (OR 4.57). Diabetes was associated with CAVIH only in women (OR 11.25). CONCLUSION: In our cohort, modifiable risk factors, particularly total cholesterol and dyslipidemia, had a different impact depending on age and sex. Targeting risk factors in selected patients might improve individual CAVIH prevention.

Acute phase of Kawasaki disease: a review of national guideline recommendations.

Key aspects of the medical management of Kawasaki disease (KD) are not yet supported by a high evidence level, thus making room for individual recommendations. We performed a structured comparison of existing international KD guidelines to analyze potential differences in the implementation of evidence-based KD recommendations regarding diagnosis and therapy. To identify country-specific guidelines, we took a multilateral approach including a comprehensive PubMed literature, online research, and directly contacting national pediatric associations. We then ran a structured guidelines' analysis and evaluated the diagnostic and therapeutic differences in the context of evidence-based medicine. In this structured guideline analysis, we identified nine national and one European guidelines. According to them all, the diagnosis of KD still relies on its clinical presentation with no reliable biomarker recommended. First-line treatment consistently involves only intravenous immunoglobulin (IVIG) therapy. Recommendations in terms of acetylsalicylic acid, corticosteroids, and additional therapeutic options vary considerably. CONCLUSION: According to all guidelines, KD is diagnosed clinically with some variance in defining incomplete KD and being a non-responder to treatment. First-line treatment consistently includes IVIG. Recommendations for additional therapeutic strategies are more heterogeneous. WHAT IS KNOWN: • The diagnosis of KD relies on the clinical presentation, entailing challenges in timely diagnosis. • Other treatment options then IVIG are not supported by a high evidence level, making room for individual recommendations. WHAT IS NEW: • Definition of incomplete KD and being non-responsive to an initial treatment vary to some extent between the national guidelines. • Only IVIG is consistently proposed throughout all guidelines, further therapeutic recommendations vary between the national recommendations.

Quality of life and patient satisfaction with outpatient care after heart transplantation in adult and pediatric patients - room for improvement?

Reduced adherence after heart transplantation increases the risk for acute rejection. Therefore, the aim of this study was to evaluate the patient's satisfaction with outpatient care and quality of life (QOL) after pediatric and adult heart transplantation. Observational study after pediatric (n = 22) and adult (n = 65) heart transplantation and the parents of the pediatric patients (n = 22) to evaluate the patients' satisfaction with outpatient care and QOL. Established standardized questionnaires were used for patient satisfaction (ZAP survey) and QOL (SF36); the latter was compared with the cohort of the BGS98 survey (BGS98 cohort). ZAP score: excellent results with almost all values >80. QOL: pediatric cohort showed significantly higher values in physical functioning (P = 0.041) and role physical (P = 0.003) but significantly lower values in the sub-scale general health (P = 0.02) compared to adult cohort. In comparison with BGS98 cohort, children showed almost similar results, whereas adult cohort showed worse values in physical and emotional functioning, but higher values regarding general health. The QOL of patients after pediatric heart transplantation is comparable to a standardized reference population in Germany, whereas adult patients show reduced physical and emotional functioning, but better values regarding general health. The patients' satisfaction with the outpatient care is very high.

Design and 3D printing of variant pediatric heart models for training based on a single patient scan.

BACKGROUND: 3D printed models of pediatric hearts with congenital heart disease have been proven helpful in simulation training of diagnostic and interventional catheterization. However, anatomically accurate 3D printed models are traditionally based on real scans of clinical patients requiring specific imaging techniques, i.e., CT or MRI. In small children both imaging technologies are rare as minimization of radiation and sedation is key. 3D sonography does not (yet) allow adequate imaging of the entire heart for 3D printing. Therefore, an alternative solution to create variant 3D printed heart models for teaching and hands-on training has been established. METHODS: In this study different methods utilizing image processing and computer aided design software have been established to overcome this shortage and to allow unlimited variations of 3D heart models based on single patient scans. Patient-specific models based on a CT or MRI image stack were digitally modified to alter the original shape and structure of the heart. Thereby, 3D hearts showing various pathologies were created. Training models were adapted to training level and aims of hands-on workshops, particularly for interventional cardiology. RESULTS: By changing the shape and structure of the original anatomy, various training models were created of which four examples are presented in this paper: 1. Design of perimembranous and muscular ventricular septal defect on a heart model with patent ductus arteriosus, 2. Series of heart models with atrial septal defect showing the long-term hemodynamic effect of the congenital heart defect on the right atrial and ventricular wall, 3. Implementation of simplified heart valves and addition of the myocardium to a right heart model with pulmonary valve stenosis, 4. Integration of a constructed 3D model of the aortic valve into a pulsatile left heart model with coarctation of the aorta. All presented models have been successfully utilized and evaluated in teaching or hands-on training courses. CONCLUSIONS: It has been demonstrated that non-patient-specific anatomical variants can be created by modifying existing patient-specific 3D heart models. This way, a range of pathologies can be modeled based on a single CT or MRI dataset. Benefits of designed 3D models for education and training purposes have been successfully applied in pediatric cardiology but can potentially be transferred to simulation training in other medical fields as well.

Rationale and feasibility of transcatheter pulmonary valve implantation in small conduits with the Edwards Sapien valves.

BACKGROUND: Conduit dilatation above 110% and TPVI in conduits <16 mm is not recommended. However, if we want to reach normal values for RVOT diameters and diminish reintervention rates, pushing these boundaries is essential. METHODS: Analysis of subsequent patients who underwent TPVI with Edwards Sapien valves in conduits ≤16 mm between 2010 and 2020. RESULTS: In n = 33 cases median age was 13 years (5-20 y) and median weight 47 kg (15-91 kg). Preexisting RVOT grafts were n = 28 Contegra® conduits and n = 5 homografts (12 mm n = 15; 14 mm n = 11; 16 mm n = 7). Implanted were the Sapien (n = 8), Sapien XT (n = 10) and Sapien 3 valve (n = 15) with 20 mm (n = 4), 23 mm (n = 19), 26 mm (n = 9) and 29 mm (n = 1). Mean minimal RVOT diameter after TPVI was 22,7 ± 2,3 mm (18-30 mm) which is 150% of the mean minimal RVOT diameter before TPVI (15,1 ± 4,3 mm). Covered stents were used in n = 10 cases. Contained conduit rupture occurred in n = 7 cases (21%). Residual RVOT gradients of 5,7 ± 4,9 mmHg (0-18 mmHg) showed adequate RV unloading. CONCLUSION: TPVI could be performed successfully in all patients. Dilatation above 150% and a valve/conduit diameter ratio up to 2,4 were well tolerated. There was a considerable amount of conduit rupture but all were confined without further need for intervention or surgery.