Fetal Echocardiography in Predicting Postnatal Outcome in Borderline Left Ventricle.

OBJECTIVES: Prenatal prediction of postnatal univentricular versus biventricular circulation in patients with borderline left ventricle (bLV) remains challenging. This study investigated prenatal fetal echocardiographic parameters and postnatal outcome of patients with a prenatally diagnosed bLV. METHODS: We report a retrospective study of bLV patients at four prenatal centers with a follow-up of one year. BLV was defined as z-scores of the left ventricle (LV) between -2 and -4. Single-ventricle palliation (SVP), biventricular repair (BVR), and no surgical or catheter-based intervention served as the dependent outcome. Prenatal ultrasound parameters were used as independent variables. Cut-off values from receiver operating characteristic curves (ROC) were determined for significant discrimination between outcomes. RESULTS: A total of 54 patients were diagnosed with bLV from 2010 to 2018. All were live births. Out of the entire cohort, 8 (15 %) received SVP, 34 (63 %) BVR, and 12 (22 %) no intervention. There was no significant difference with regard to genetic or extracardiac anomalies. There were significantly more patients with endocardial fibroelastosis (EFE) in the SVP group compared to the BVR group (80 % vs. 10 %), (p < 0.001). Apex-forming LV (100 % vs. 70 %) and lack of retrograde arch flow (20 % vs. 80 %) were associated with no intervention (p < 0.001). With respect to BVR vs. SVP, the LV sphericity index provided the highest specificity (91.7 %) using a cutoff value of ≤ 0.5. CONCLUSION: The majority of bLV patients maintained biventricular circulation. EFE, retrograde arch flow, and LV sphericity can be helpful parameters for counseling parents and further prospective studies can be developed.

Natural history of pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (CPS) and prediction of outcome.

OBJECTIVES: To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS). METHODS: We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 (< 24 weeks), 2 (24-30 weeks) and 3 (> 30 weeks). RESULTS: 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p < 0.001). Tricuspid insufficiency (TI)-Vmax > 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax < 2.5 m/s, TV/MV ratio < cutoff) to a score, non-BV outcome was correctly predicted when > 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention. CONCLUSION: TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated.

Pediatric cardiac waitlist mortality-Still too high.

Cardiac transplantation for children with end-stage cardiac disease with no other medical or surgical options is now standard. The number of children in need of cardiac transplant continues to exceed the number of donors considered "acceptable." Therefore, there is an urgent need to understand which recipients are in greatest need of transplant before becoming "too ill" and which "marginal" donors are acceptable in order to reduce waitlist mortality. This article reviewed primarily pediatric studies reported over the last 15 years on waitlist mortality around the world for the various subgroups of children awaiting heart transplant and discusses strategies to try to reduce the cardiac waitlist mortality.

Anesthesia for bilateral pulmonary banding as part of hybrid stage I approach palliating neonates with hypoplastic left heart syndrome.

BACKGROUND: Neonatal management of patients with hypoplastic left heart syndrome and complex remains a challenging task, whereby the "hybrid" palliation is often reserved for high-risk patients as a "rescue" procedure. AIM: This study documents the anesthetic challenges and potential complications associated with the Giessen hybrid stage I approach. METHODS: The Giessen hybrid stage I approach is focused on surgical bilateral pulmonary artery banding. Retrospective perioperative data were analyzed. Contrary to a stable group A, inotropic treatment before surgery for treatment of postnatal shock classified patients as unstable (Group B). Clinical outcomes considered were inhospital mortality, duration of postoperative mechanical ventilation, postoperative time at the intensive care unit, perioperative vasoactive medication requirements, and red blood cell transfusion. RESULTS: From June 1998 to December 2015, 185 patients were allocated to Group A (n = 165) and Group B (n = 20). The inhospital mortality was 2.2% with no difference between the groups. There was also no difference in the postoperative time on mechanical ventilation and the time in the intensive care unit. Vasoactive medication was more often required in Group B (100%) compared to Group A (19%). In Group B, more red blood cells were transfused 6.0 ± 8.3 vs 2.0 ± 5.8 mL/kg in Group A (P < .05, 95% CI 0.0 - 2.6). CONCLUSION: Considering a learning curve, anesthesia for surgical bilateral pulmonary artery banding palliating patients with hypoplastic left heart syndrome and complex can safely be performed, independent from the preoperative clinical status.

Outcome and Associated Findings in Individuals with Pre- and Postnatal Diagnosis of Tetralogy of Fallot (TOF) and Prediction of Early Postnatal Intervention.

PURPOSE: The aim of our retrospective evaluation was to compare the outcome of patients with prenatal and postnatal diagnosis of Tetralogy of Fallot (TOF) and to analyze prenatal echocardiographic parameters predicting intervention within 30 days postnatal. MATERIALS AND METHODS: We evaluated 142 patients in our pediatric heart center and prenatal diagnosis center and prenatal practice Praenatal plus in Cologne between 01/08-06/16. RESULTS: Within the prenatal diagnosis group, 6/74 fetuses (8.1 %) had TOF with pulmonary atresia (TOF-PA), and 6 (8.1 %) had absent pulmonary valve syndrome (TOF-APVS). 14 (18.9 %) had an abnormal karyotype including 9/14 (64.3 %) with microdeletion 22q11.2. 25 (33.8 %) had extracardiac malformation. 4 (5.4 %) had agenesis of ductus arteriosus (DA), 22 (29.7 %) had right aortic arch (RAA) and 9 (12.2 %) had major aortopulmonary collateral arteries (MAPCAs). Within the postnatal diagnosis group, no patient had TOF-PA, 4/68 (5.9 %) had TOF-APVS. 12 (17.6 %) had extracardiac malformations, 9 (13.2 %) had an abnormal karyotype including 2/9 with microdeletion 22q11.2. 10 (14.7 %) had RAA, 9 (13.2 %) had MAPCAs. There were no cases with agenesis of DA. Increasing z-score values of the left/right pulmonary artery (LPA/RPA) prenatally were associated with a lower probability for early postnatal intervention (RPA: p = 0.017; LPA: p = 0.013). Within the prenatal diagnosis group, 12 of 41 (29.3 %) live-born patients with follow-up and intention to treat needed early intervention versus 7 (10.3 %) in the postnatal diagnosis group (p = 0.02). Within the postnatal diagnosis group, there were no deaths, while 2 (4.9 %) post-intervention deaths occurred in the prenatal diagnosis group. CONCLUSION: There are no significant differences concerning post-intervention survival in the prenatal diagnosis group versus the postnatal diagnosis group. Complex cases may be underrepresented in the postnatal diagnosis group. Smaller RPA/LPA values prenatally seem to be associated with early postnatal intervention.

Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: palliative treatment with a rapamycin analog.

Noonan syndrome with multiple lentigines (NSML) frequently manifests with hypertrophic cardiomyopathy (HCM). Recently, it was demonstrated that mTOR inhibition reverses HCM in NSML mice. We report for the first time on the effects of treatment with a rapamycin analog in an infant with LS and malignant HCM. In the boy, progressive HCM was diagnosed during the first week of life and a diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in PTPN11. Immunoblotting with antibodies against pERK, pAkt, and pS6RP in fibroblasts demonstrated enhanced Akt/mTOR pathway activity. Because of the patient's critical condition, everolimus therapy was started at age 24 weeks and continued until heart transplantation at age 36 weeks. Prior to surgery, heart failure improved from NYHA stage IV to II and brain natriuretic peptide values decreased from 9,600 to <1,000 pg/ml, but no reversal of cardiac hypertrophy was observed. Examination of the explanted heart revealed severe hypertrophy and myofiber disarray with extensive perivascular fibrosis. These findings provide evidence that Akt/mTOR activity is enhanced in NSML with HCM and suggest that rapamycin treatment could principally be feasible for infantile NSML. The preliminary experiences made in this single patient indicate that therapy should start early to prevent irreversible cardiac remodelling.

Fifteen-year single center experience with the "Giessen Hybrid" approach for hypoplastic left heart and variants: current strategies and outcomes.

Presented is a retrospective outcome study of a 15-year single institutional experience with a contemporary cohort of patients with hypoplastic left heart syndrome and complex that underwent a "Giessen Hybrid" stage I as initial palliation. Hybrid approach consisting of surgical bilateral pulmonary artery banding and percutaneous duct stenting with or without atrial septum manipulation was developed from a rescue approach to a first-line procedure. Comprehensive Aristotle score defined pre-operative condition. Fifteen-year follow-up mortality is reported as occurring within the staged univentricular palliation or before and after biventricular repair. Hybrid stage I was performed in 154 patients; 107 should be treated by single ventricle palliation, 33 by biventricular repair (BVR), 7 received heart transplantation, and 7 were treated by comfort care, respectively. Overall 34 children died. The Aristotle score (mean value 18.2 ± 3) classified for univentricular circulations in newborns did not have statistical impact on the outcome. Two patients died during stage I (1.2%), and the interstage I mortality was 6.7%, and stage II mortality 9%, respectively. Stage III was up to now performed in 57 patients without mortality. At 1 year, the overall unadjusted survival of HLHS and variants was 84% and following BVR 89%, respectively. The Fifteen-year survival rate for HLHS and variants was 77%, with no significant impact of birth weight of less than 2.5 kg. In conclusion, Hybrid stage I fulfilled the criteria of life-saving approach. In our institution, Hybrid procedure replaced Norwood-staged palliation with a considerable mid- and long-term survival rate. Considering interstage mortality close surveillance is mandatory.

Pediatric heart allocation and transplantation in Eurotransplant.

Pediatric heart allocation in Eurotransplant (ET) has evolved over the past decades to better serve patients and improve utilization. Pediatric heart transplants (HT) account for 6% of the annual transplant volume in ET. Death rates on the pediatric heart transplant waiting list have decreased over the years, from 25% in 1997 to 18% in 2011. Within the first year after listing, 32% of all infants (<12 months), 20% of all children aged 1-10 years, and 15% of all children aged 11-15 years died without having received a heart transplant. Survival after transplantation improved over the years, and in almost a decade, the 1-year survival went from 83% to 89%, and the 3-year rates increased from 81% to 85%. Improved medical management of heart failure patients and the availability of mechanical support for children have significantly improved the prospects for children on the heart transplant waiting list.

Left Ventricular Physiology and Ventricular-Vascular Interactions in Young Patients After Heart Transplantation.

Background In patients after heart transplantation, systemic arterial hypertension and enhanced central aortic stiffness contribute to increased ventricular afterload, which might lead to graft dysfunction. The aim of our study was to characterize systemic arterial elastance and its impact on left ventricular function and ventriculo-arterial coupling in a cohort of children, adolescents, and young adults after heart transplantation using invasive conductance catheter technique. Methods and Results Thirty patients who had heart transplants (age, 20.0±6.5 years, 7 female) underwent invasive cardiac catheterization including pressure-volume loop analysis. Load-independent parameters of systolic (ventricular elastance [Ees]) and diastolic (ventricular compliance) function as well as systemic arterial elastance (Ea, end-systolic pressure/stroke volume) and ventriculo-arterial coupling (Ea/Ees) were assessed at baseline level and during dobutamine infusion (10 µg/kg/min). Ees showed an appropriate increase under inotropic stimulation from 0.43 (0.11-2.52) to 1.00 (0.20-5.10) mm Hg/mL/m2 (P<0.0001), whereas ventricular compliance remained rather unchanged (0.16±0.10 mm Hg/mL/m2 to 0.12±0.07 mm Hg/mL/m2; P=0.10). Ventriculo-arterial coupling Ea/Ees was abnormal at rest and did not improve significantly under dobutamine (1.7 [0.6-6.7] to 1.3 [0.5-4.9], P=0.70) due to a simultaneous rise in Ea from 0.71 (0.37-2.82) to 1.10 (0.52-4.03) mm Hg/mL/m2 (P<0.0001). Both Ees and ventricular compliance were significantly associated with Ea at baseline and under dobutamine infusion. Conclusions Patients who underwent heart transplantation show impaired ventriculo-arterial coupling at rest and under inotropic stimulation despite preserved left ventricular contractile reserve. An abnormal response in vascular function resulting in increased afterload seems to represent an important factor that may play a role for the development of late graft failure.

Renal function in children with heart transplantation after switching to CNI-free immunosuppression with everolimus.

Renal impairment because of CNI contributes to long-term morbidity. Therefore, CNI avoiding or sparing treatment strategies are important. In this article, we describe the results of a CNI-free treatment protocol with regard to recovery of renal function. Twenty-eight patients with heart transplantation were switched from CNI regimen to everolimus and mycophenolate, when cGFR was <75 mL/min/1.73 m(2). In all patients, CNI was stopped, when everolimus trough levels of 5-8 ng/L were achieved. Serum creatinine and cGFR were determined before and after 6 and 12 months. Median serum creatinine decreased from 1.2 mg/dL (range 0.7-3.7) before everolimus to 1.0 (range 0.6-1.8) and 1.0 (range 0.5-1.9) mg/dL after 6 and 12 months. Median cGFR was 47.81 (range 18.3-72.6) mL/min/1.73 m(2) before everolimus and 63.1 (range 37.8-108.7) mL/min/1.73 m(2) at six months and 64.8 (range 37.7-106.6) mL/min/1.73 m(2) after 12 months. All changes from baseline to six and 12 months were statistically significant (p < 0.05). Adverse events were infections (n = 3) and rejections (n = 3). Therapy was discontinued in four patients. Conversion to CNI-free immunosuppression resulted in significant improvements of renal function within six months of CNI withdrawal. Side effects are common. However, more studies are required to demonstrate the effectiveness in children.

Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R).

AIM: Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. METHODS AND RESULTS: The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. CONCLUSION: The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

Aetiology and 30-Year Long-Term Outcome of Children with Cardiomyopathy Necessitating Heart Transplantation.

Studies assessing the long-term outcome after heart transplantation HTX in patients with cardiomyopathy (CM) in the paediatric age range are rare. The aim of this study was to determine the survival rate of children with CM undergoing HTX and to analyse how aetiology of cardiomyopathy influenced morbidity and mortality. We retrospectively analysed the medical records of children; who were transplanted in our centre between June 1988 and October 2019. 236 heart transplantations were performed since 1988 (9 re-transplants). 98 of 227 patients (43.2%) were transplanted because of CM. Survival rates were 93% after 1; 84% after 10 and 75% after 30 years. Overall; the aetiology of CM could be clearly identified in 37 subjects (37.7%). This rate increased up to 66.6% (12/19) by applying a comprehensive diagnostic workup since 2016. The survival rate was lower (p < 0.05) and neurocognitive deficits were more frequent (p = 0.001) in subjects with systemic diseases than in individuals with cardiac-specific conditions. These data indicate that the long-term survival rate of children with CM after HTX in experienced centers is high. A comprehensive diagnostic workup allows unraveling the basic defect in the majority of patients with CM undergoing HTX. Aetiology of CM affects morbidity and mortality in subjects necessitating HTX.

Clinical characteristics and outcomes of patients with adult congenital heart disease listed for heart and heart‒lung transplantation in the Eurotransplant region.

BACKGROUND: The therapeutic success in patients with congenital heart disease (CHD) leads to a growing number of adults with CHD (adult CHD [ACHD]) who develop end-stage heart failure. We aimed to determine patient characteristics and outcomes of ACHD listed for heart transplantation. METHODS: Using data from all the patients with ACHD in 20 transplant centers in the Eurotransplant region from 1999 to 2015, we analyzed patient characteristics, waiting list, and post-transplantation outcomes. RESULTS: A total of 204 patients with ACHD were listed during the study period. The median age was 38 years, and 62.3% of the patients were listed in high urgency (HU), and 37.7% of the patients were in transplantable (T)-listing status. A total of 23.5% of the patients died or were delisted owing to clinical worsening, and 75% of the patients underwent transplantation. Median waiting time for patients with HU-listing status was 4.18 months and with T-listing status 9.07 months. There was no difference in crude mortality or delisting between patients who were HU status listed and T status listed (p = 0.65). In multivariable regression analysis, markers for respiratory failure (mechanical ventilation, hazard ratio [HR]: 1.41, 95% CI: 1.11-1.81, p = 0.006) and arrhythmias (anti-arrhythmic medication, HR: 1.42, 95% CI: 1.01-2.01, p = 0.044) were associated with a higher risk of death or delisting. In the overall cohort, post-transplantation mortality was 26.8% after 1 year and 33.4% after 5 years. CONCLUSIONS: Listed patients are at high risk of death without differences in the urgency of listing. Respiratory failure requiring invasive ventilation and possibly arrhythmias requiring anti-arrhythmic medication indicate worse outcomes on waiting list.

Hemodynamic effects of dobutamine and dopexamine after cardiopulmonary bypass in pediatric cardiac surgery.

BACKGROUND: After surgical repair of congenital heart disease, inotropic support is sometimes necessary to wean from cardiopulmonary bypass. In pediatric cardiac surgery, dobutamine and dopamine are often used as inotropic support. Dopexamine is a synthetic catecholamine, which has positive inotropic and vasodilating properties. Because the hemodynamic effects of catecholamines are modified after cardiopulmonary bypass, the aim of this study was to investigate the effects of dobutamine and dopexamine on cardiac index and systemic vascular resistance index after cardiopulmonary bypass in pediatric cardiac surgery. METHODS: The study was performed in a prospective, randomized, and double-blinded cross-over design. The investigation included 11 children for elective, noncomplex congenital heart surgery. After weaning from cardiopulmonary bypass and a 20-min period of steady state, children received either 2.5 microg x kg(-1) x min(-1) dobutamine or 1 microg x kg(-1) x min(-1) dopexamine for 20 min. Cardiac index (transpulmonary thermodilution), mean arterial pressure, central venous pressure, stroke volume, systemic vascular resistance, and central venous oxygen saturation were determined. The primary outcome variable was cardiac index. RESULTS: No difference in cardiac index was observed between the two groups (P = 0.594). Both drugs increased cardiac index, dopexamine from 3.9 +/- 0.6 to 4.7 +/- 0.8 l x min(-1) x m(-2) (P = 0.003) and dobutamine from 4.1 +/- 0.7 to 4.8 +/- 0.7 l x min(-1) x m(-2) (P = 0.004). During treatment with dobutamine, children presented with significantly higher mean arterial pressure (P = 0.003) and systemic vascular resistance index (P = 0.026). CONCLUSIONS: This trial demonstrates that low-dose dobutamine and dopexamine both increase cardiac index during pediatric cardiac surgery but with different hemodynamic effects.

Ideal intensive care unit course following comprehensive stage II in hypoplastic left heart syndrome.

Comprehensive stage II is the advanced surgical part of the staged treatment of a newborn with hypoplastic left heart syndrome (HLHS) palliated initially by a Giessen-Hybrid approach. We report an almost ideal course following comprehensive stage II operation with focus on postoperative intensive care strategy. Following a short introduction of the postnatally performed Giessen-Hybrid approach, in which the surgical part is focused on bilateral pulmonary banding and duct stenting as well as manipulation of the atrial septum is postponed to transcatheter approach, it should be emphasized, that the quality of inter-stage I is eminently important for the success of the following comprehensive stage II. Furthermore, the interplay of the responsible surgeon, anesthesiologist, cardiologist and intensivist is mandatory for working as a team with a similar pathophysiological background. Presupposed a sophisticated surgical and anesthesiologic management, the immediate post-operative intensive care is crucial for the patient's final outcome, not only in terms of mortality but even morbidity (long-term neurological condition). Detailed treatment strategies are presented by pathophysiological reasonable hypotheses and the current pharmacological knowledge. Aiming to improve systemic and regional oxygen delivery and lowering oxygen consumption, as a sine qua none for a favorable patient's outcome.

Improvement of survival in low-weight children on the Berlin Heart EXCOR ventricular assist device support†.

OBJECTIVES: Publications on the paediatric Berlin Heart EXCOR ventricular assist device have revealed that low body weight <10 kg is a significant risk factor for mortality with children weighing <5 kg being at the highest risk. However, these studies are limited to implantation periods prior to 2011. Since then, progress has been made in the optimization of patient selection and management. This study investigated whether the survival of children weighing <10 kg supported with the EXCOR assist device has improved in recent years and sought to determine the risk factors for mortality. METHODS: The Berlin Heart EXCOR prospective registry (n = 1832) was retrospectively reviewed between 2000 and 2017 to compare the outcomes of different weight cohorts: A (<5 kg; n = 204), B (5-10 kg; n = 633) and C (>10 kg; n = 995) in different eras [era 1: January 2000-December 2012 (n = 1089) and era 2: January 2013-June 2017 (n = 743)]. RESULTS: Overall survival in groups A and B significantly increased from era 1 to era 2 (group A 51% vs 65%, P < 0.001; group B 74% vs 78%, P = 0.001), whereas it remained stable in group C (78% vs 73%). In era 2, the survival of group B was not significantly different from group C. On the multivariable analysis of children weighing <5 kg, congenital heart disease, preoperative extracorporeal life support and biventricular support were independently associated with increased mortality in era 1 [hazard ratio 2.04 (95% confidence interval 1.18-3.53); 2.44 (1.36-4.37) and 1.93 (1.11-3.34), respectively] but not in era 2. CONCLUSIONS: Paediatric EXCOR ventricular assist device therapy has significantly improved for patients weighing <10 kg. Withholding a ventricular assist device is not justified on the basis of the body weight alone.

Anesthesia for Pediatric Heart Transplantation: Are Patients With a Failing Hemi-Fontan- or Fontan-Physiology Different?

Background. The absolute number of patients presenting with failure of the hemi-Fontan or Fontan circulation for cardiac transplantation (cTx) will continuously rise. We aimed to analyze the intraoperative differences in patients undergoing cTx for a failing hemi-Fontan or Fontan circulation (group A) with those undergoing cTx for cardiomyopathy and congenital heart disease (group B). Methods. Data of patients undergoing cTx during a 10-year period were compared between group A and group B patients. Results. cTx was performed in 83 patients (group A, n = 21; group B, n = 62). Surgical times including median incision-suture time (549 minutes vs 386 minutes, P < .05) and median organ ischemia time (305 minutes vs 233 minutes, P < .05) were longer in group A patients. After weaning off cardiopulmonary bypass a higher median modified Vasoactive Inotropic Score (16 vs 10, P < .05) was necessary in group A patients. During surgery more fresh frozen plasma (44 mL/kg vs 20 mL/kg, P < .05), platelet concentrates (20 mL/kg vs 14 mL/kg, P < .05), and coagulation factor concentrates were given in group A patients. Mortality during the first 90 days after cTx was higher in group A (23.8% vs 6.5%, P < .05). Conclusion. Patients undergoing cTx for a failing hemi-Fontan or Fontan circulation are challenging. They require an intensive vasoactive and inotropic support; furthermore, special attention should be paid to the management of bleeding complications. cTx for this group of patients is associated with higher 90 days mortality.

Genetic basis of hypertrophic cardiomyopathy in children.

BACKGROUND: Previous investigations assessing the genetic cause of pediatric hypertrophic cardiomyopathy (HCM) found underlying genetic mutations in 50-60% of cases. The purpose of our study was to analyze whether this number can be augmented by applying next-generation sequencing and directing further diagnostics by discussing unsolved cases in a multidisciplinary board. METHODS AND RESULTS: 42 patients with the diagnoses of HCM made before age 18 years were treated in our center from 2000 to 2016. Genetic analysis was performed in 36 subjects, a genetic defect was detected in 29 (78%) patients. 15 individuals (42%) had pathogenic variants in genes encoding sarcomere proteins, and 5 (14%) in genes coding for components of the RAS/MAPK signaling pathway. 4 subjects (11%) had mutations in the GAA gene (Pompe disease), and 3 (8%) had Frataxin repeat expansions (Friedreich's ataxia). One patient each showed a mutation in BAG3 and LMNA. Discussion of unsolved HCM cases after performing next-generation sequencing (28 genes) in an interdisciplinary board unraveled the genetic cause in 9 subjects (25%). CONCLUSION: A definite genetic diagnosis can be reached in nearly 80% with HCM of childhood onset. Next-generation sequencing in conjunction with a multidisciplinary cooperation can enhance the diagnostic yield substantially. This may be important for risk stratification, treatment planning and genetic counseling.

Reduced Biventricular Volumes and Myocardial Dysfunction Long-term After Pediatric Heart Transplantation Assessed by CMR.

BACKGROUND: Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function. METHODS: Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y). RESULTS: LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (-12 ± 6 versus -15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (ß = -0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance. CONCLUSIONS: Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.

Antithrombotic therapy in pediatric ventricular assist devices: Multicenter survey of the European EXCOR Pediatric Investigator Group.

OBJECTIVES: Mechanical circulatory support for pediatric heart failure patients with the Berlin Heart EXCOR ventricular assist system is the only approved and established bridging strategy for recovery or heart transplantation. In recent years, the burden of thromboembolic events has led to modifications of the recommended antithrombotic therapy. Therefore, we aimed to assess modifications of antithrombotic practice among the European EXCOR Pediatric Investigator Group members. METHODS: We sent a questionnaire assessing seven aspects of antithrombotic therapy to 18 European hospitals using the EXCOR device for children. Returned questionnaires were analyzed and identified antithrombotic strategies were descriptively compared to "Edmonton protocol" recommendations developed for the US EXCOR pediatric approval study. RESULTS: Analysis of 18 received surveys revealed substantial deviations from the Edmonton protocol, including earlier start of heparin therapy at 6-12 h postoperatively and in 50% of surveyed centers, monitoring of heparin effectiveness with aPTT assay, administering vitamin K antagonists before 12 months of age. About 39% of centers use higher international normalized ratio targets, and platelet inhibition is changed in 56% including the use of clopidogrel instead of dipyridamole. Significant inter-center variability with multiple deviations from the Edmonton protocol was discovered with only one center following the Edmonton protocol completely. CONCLUSION: Current antithrombotic practice among European EXCOR users representing the treatment of more than 600 pediatric patients has changed over time with a trend toward a more aggressive therapy. There is a need for systematic evidence-based evaluation and harmonization of developmentally adjusted antithrombotic management practices in prospective studies toward revised recommendations.