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Background: Data on closure of atrial septal defects (ASD) in elderly patients with a fenestrated Amplatzer septal occluder (ASO) device is limited. Methods: A hemodynamically significant ASD was closed with a fenestrated ASO in 3 patients with ages >62 years. Prior to implant a 4-mm fenestration was created by balloon dilatation without additional suture fixation just adjacent to the stent part of the device. Indications for fenestration were restrictive left ventricular physiology and/or pulmonary hypertension. Heparin had been administered during and for 48 hours after the procedure. Two patients were maintained on phenprocoumon because of chronic atrial fibrillation, the remaining patient on aspirin and clopidogrel for 3 months after implant. Transesophageal echocardiography (TEE) and hemodynamic evaluation were performed 4-18 months after ASD closure. Results: A trace or small fenestration through the ASO with left-to-right shunt was detected by TEE in all 3 patients without any hemodynamic significance. No thrombus formation was observed. Pulmonary hypertension improved in the affected patient. Pulmonary arterial wedge pressure and cardiac index improved in the second patient with improvement in heart failure symptoms and of quality of life in both. The third patient, after initial improvement for 6 months, developed significant comorbidities and clinical deterioration at 18 months follow-up. Conclusion: The modified fenestration of the ASO decreased significantly in size at follow-up. Applying this technique to selected patients judged to be at risk for ASD closure avoids acute decompensation and allows gradual diminuition of right ventricular volume overload during mid-term follow-up. (J Interven Cardiol 2011;24:485-490) [ABSTRACT FROM AUTHOR]

Objective: Despite their clinical introduction 10 years ago, no human series on the healing response to Amplatzer and Starflex devices in humans have been reported yet. We sought to investigate the biocompatibility of Amplatzer and Cardioseal/Starflex septal occluder devices in humans and compare the findings to results in experimental animals. Methods: The healing response of Amplatzer and Cardioseal/Starflex septal occluder devices in humans (n = 12, follow-up periods from 5 days to 4 years) and in experimental animals (n = 32, follow-up periods from 4 days to 1 year) was studied using a uniform work up protocol. Histological sections of paraffin-wax- embedded or methacrylate-embedded specimen and scanning electron microscopy were used for biocompatibility screening. Results: Neoendothelialisation of all examined devices was complete after 3 months in vivo. Protruding metal frame parts, like screw threads and spring arms, were covered last. The initial deposition of fibrin and blood cells on the polyester fabric was subsequently organised by ingrown fibroblastic cells. Loosely arranged and poorly vascularised young granulation tissue was transformed time-dependently into quiescent fibre-rich connective repair tissue poor of cellular and capillary vessel components. Consistently, a mild chronic inflammatory response directed against textile fibres of both types of implants characterised by lymphocytic infiltration and multinucleated foreign body giant cells was observed equally in human and animal explants. Conclusions: Systematic biocompatibility screening in a series of explanted human septal occluder devices showed results corresponding to findings in animal studies with regard to neoendothelialisation, cellular organisation of initial thrombus and persisting immune response. [ABSTRACT FROM AUTHOR]

Objectives: We sought to test the hypothesis that interventional atrial septal defect (ASD) closure can be performed safely and effectively using a bioresorbable occluder matrix. Background: The ideal septal occluder scaffold should promote the healthiest and most complete healing response while eventually facilitating the full resorption of the material and leaving “native” tissue behind, thus minimizing the potential for future complications from chronic foreign body and maintaining the possibility for later unobstructed transseptal access to the left atrium. Methods: The STARFlex occluders (NMT Medical Inc., Boston, Massachusetts) were modified by substituting the conventional polyester fabric for a bioengineered, acellular type-I collagen matrix derived from porcine submucosa with a heparin-coated surface (BioSTAR occluder, NMT Medical Inc.). Comparative transcatheter closure of ASDs was performed in young sheep (n = 36). Gross pathology and histopathology were obtained after follow-up periods ranging from 7 days to 2 years. Results: The STARFlex (control) devices were encapsulated time-dependently by ingrown fibrous tissue. Histology showed a mild but chronically persisting foreign body reaction. By contrast, BioSTAR devices exhibited a mild-to-moderate transient cellular immune response. Heparin coating of the BioSTAR surface improved the biocompatibility of the device by reducing surface thrombogencity. A remodeling process of the collagen scaffold, starting after 30 days in vivo, resulted in the full replacement of the matrix by host tissue after 2 years of follow-up. Conclusions: The BioSTAR device is the first septal occluder with a totally bioresorbable matrix that is fully replaced by host tissue during the healing process. The promising results of this study support testing of the BioSTAR device in clinical trials. [Copyright &y& Elsevier]

The ideal septal occluder scaffold should promote the healthiest and most complete healing response possible while eventually facilitating the full resorption of the material, leaving “native” tissue behind. An excellent biocompatibility of the scaffold tissue is a prerequisite for quick, complete, and firm ingrowth of the device, optimizing outcomes and minimizing the potential for complications. Intestinal collagen layer (ICL) is a highly purified (acellular) bioengineered type-1 collagen derived from porcine submucosa. It is gradually resorbed by the host organism and subsequently replaced by the host tissue. CardioSEAL® occluders were modified by substituting the conventional polyester fabric for an intestinal collagen layer (ICL). Percutaneous transcatheter closure of interventionally created atrial septal defects was performed in lambs using these modified occluders. A complete pathomorphological investigation including histology was carried out after 2, 4, and 12 weeks follow-up. Standard CardioSEAL implants served as a control group. After 2 weeks in vivo the devices were already covered completely by neo-endothelium. Compared with the conventional synthetic scaffold, ICL devices showed a quicker endothelialization, decreased thrombogenicity, and superior biocompatibility with no significant cellular infiltration observed in the histology of explants with ICL fabrics. After 3 months in vivo the collagen layer remained mechanically intact, but began to show the first histological signs of mild disintegration, gradual resorption, and remodeling. In conclusion, short-term results from preliminary in vivo experiments using a bioengineered collagen matrix as the occluder tissue scaffold showed excellent biocompatibility. This resulted in superior overall results: quicker endothelialization, a decreased thrombogenicity, and decreased immunological host response. (J Interven Cardiol 2003;16:149–152). [ABSTRACT FROM AUTHOR]

Objective: Atrial septal defect (ASD) occluders are permanent implants in paediatric cardiology which serve as mechanical shields until complete overgrowth and incorporation of the occluding device by autologous tissue has occurred. Thereafter, the foreign body material making up the device is dispensable and bears potential long-term adverse effects. Rapid, firm and complete incorporation into the atrial septal wall should be a prerequisite for biodegradable devices. In this study, the feasibility of using autologous cell-seeded devices was investigated by (a) testing the influence of a collagen coating on cellular stress resistance in vitro and (b) comparing the short-term effects between cell-seeded, collagen-coated and acellular ASD occluders in vivo. Methods: Native and collagen-coated Dacon fabrics and Starflex-devices were pre-seeded with autologous fibroblasts (skin biopsy) and evaluated using various mechanical stress tests. In a sheep model interventionally created ASDs were closed using either autologous pre-seeded or conventional (acellular) Starflex-devices. Results: ASD closure devices were successfully pre-seeded with autologous cells. The incubation period needed, the cellular density achieved and the mechanical stability of the cytolayer after mechanical stressing (implantation) were improved by applying a collagen matrix on the fabric. Compared to the thin layer of ingrown tissue seen on conventional occluders after 30 days in vivo, a thicker layer of organising, newly formed granulation tissue on pre-seeded collagen-coated devices embedded not only the Dacron fabric, but also completely covered the spring arms of the device underneath a layer of neo-endothelium. Conclusion: Autologous cell pre-seeding of interventional closure devices is feasible since the cells survive the mechanical stress encountered during implantation. Rapid, firm and complete ingrowth of occluder devices into a thicker layer of young fibrous granulation tissue can be achieved, but an increased thrombogenicity currently limits the in vivo application. [ABSTRACT FROM PUBLISHER]

Cardiomyocyte maturation during pre- and postnatal development requires multiple intertwined processes, including a switch in energy generation from glucose utilization in the embryonic heart towards fatty acid oxidation after birth. This is accompanied by a boost in mitochondrial mass to increase capacities for oxidative phosphorylation and ATP generation required for efficient contraction. Whether cardiomyocyte differentiation is paralleled by augmented capacities to deal with reactive oxygen species (ROS), physiological byproducts of the mitochondrial electron transport chain (ETC), is less clear. Here we show that expression of genes and proteins involved in redox homeostasis and protein quality control within mitochondria increases after birth in the mouse and human heart. Using primary embryonic, neonatal and adult mouse cardiomyocytes in vitro we investigated how excessive ROS production induced by mitochondrial dysfunction affects cell survival and stress response at different stages of maturation. Embryonic and neonatal cardiomyocytes largely tolerate inhibition of ETC complex III by antimycin A (AMA) as well as ATP synthase (complex V) by oligomycin but are susceptible to complex I inhibition by rotenone. All three inhibitors alter the intracellular distribution and ultrastructure of mitochondria in neonatal cardiomyocytes. In contrast, adult cardiomyocytes treated with AMA undergo rapid morphological changes and cellular disintegration. At the molecular level embryonic cardiomyocytes activate antioxidative defense mechanisms, the integrated stress response (ISR) and ER stress but not the mitochondrial unfolded protein response upon complex III inhibition. In contrast, adult cardiomyocytes fail to activate the ISR and antioxidative proteins following AMA treatment. In conclusion, our results identified fundamental differences in cell survival and stress response in differentiated compared to immature cardiomyocytes subjected to mitochondrial dysfunction. The high stress tolerance of immature cardiomyocytes might allow outlasting unfavorable intrauterine conditions thereby preventing fetal or perinatal heart disease and may contribute to the regenerative capacity of the embryonic and neonatal mammalian heart. [Display omitted] • Capacities for redox homeostasis increase parallel to cardiomyocyte maturation. • Embryonic and neonatal cardiomyocytes largely tolerate mitochondrial dysfunction. • The site of mitochondrial ROS generation determines outcome in immature cardiomyocytes. • Adult cardiomyocytes are highly susceptible to mitochondrial dysfunction. • Cardiomyocyte maturation alters the molecular response to mitochondrial impairment. [ABSTRACT FROM AUTHOR]

We aimed to evaluate retrospectively associated anomalies and outcome in prenatal aortic arch anomalies (AAAs). We included ninety patients with aberrant right subclavian artery (ARSA), right aortic arch (RAA) with mirror image branching (RAA-mirror) or aberrant left subclavian artery (RAA-ALSA) and double aortic arch (DAA) between 2011 and 2020. In total, 19/90 (21.1%) had chromosomal anomalies, the highest rate being within the ARSA subgroup (17/46, 37%). All (13/13) of the RAA-mirror subgroup, 10/27 (37.0%) of RAA-ALSA, 13/46 (28.3%) of ARSA and 0/4 within the DAA subgroup had additional intracardiac anomaly. The rate of extracardiac anomalies was 30.7% in RAA-mirror, 28.3% in ARSA, 25.0% in DAA and 22.2% in the RAA-ALSA subgroup. A total of 42/90 (46.7%) had isolated AAAs: three (7.1%) with chromosomal anomalies, all trisomy 21 (3/26, 11.5%) within the ARSA subgroup. Out of 90, 19 (21.1%) were lost to follow-up (FU). Two (2.2%) intrauterine deaths occurred, and six (6.7%) with chromosomal anomalies terminated their pregnancy. In total, 63 (70.0%) were liveborn, 3/63 (4.8%) with severe comorbidity had compassionate care and 3/60 (5.0%) were lost to FU. The survival rate in the intention-to-treat cohort was 53/57 (93%). Forty-one (77.4%) presented with vascular ring/sling, two (4.9%) with RAA-ALSA developed symptoms and one (2.4%) needed an operation. We conclude that intervention due to vascular ring is rarely necessary. NIPT could be useful in isolated ARSA cases without higher a priori risk for trisomy 21 and after exclusion of other anomalies. [ABSTRACT FROM AUTHOR]

We present results of the histopathological work-up of an atrial septal defect occluder that was explanted 15 months after interventional implantation due to a significant residual shunt. Complete endothelialization of the surface and a mild inflammatory reaction was demonstrated. [ABSTRACT FROM AUTHOR]

RASopathies are caused by mutations in genes that alter the MAP kinase pathway and are marked by several malformations with cardiovascular disorders as the predominant cause of mortality. Mechanistic insights in the underlying pathogenesis in affected cardiac tissue are rare. The aim of the study was to assess the impact of RASopathy causing mutations on the human heart. Using single cell approaches and histopathology we analyzed cardiac tissue from children with different RASopathy-associated mutations compared to age-matched dilated cardiomyopathy (DCM) and control hearts. The volume of cardiomyocytes was reduced in RASopathy conditions compared to controls and DCM patients, and the estimated number of cardiomyocytes per heart was ∼4–10 times higher. Single nuclei RNA sequencing of a 13-year-old RASopathy patient (carrying a PTPN11 c.1528C > G mutation) revealed that myocardial cell composition and transcriptional patterns were similar to <1 year old DCM hearts. Additionally, immaturity of cardiomyocytes is shown by an increased MYH6/MYH7 expression ratio and reduced expression of genes associated with fatty acid metabolism. In the patient with the PTPN11 mutation activation of the MAP kinase pathway was not evident in cardiomyocytes, whereas increased phosphorylation of PDK1 and its downstream kinase Akt was detected. In conclusion, an immature cardiomyocyte differentiation status appears to be preserved in juvenile RASopathy patients. The increased mass of the heart in such patients is due to an increase in cardiomyocyte number (hyperplasia) but not an enlargement of individual cardiomyocytes (hypertrophy). [Display omitted] • Pediatric patients with RASopathies exhibit an increased heart mass. • Cardiomyocyte size and volume are reduced in pediatric patients with RASopathies. • Cardiomyocyte numbers per heart are increased in pediatric RASopathy patients. • Cardiomyocytes in juvenile RASopathy have an immature state. • Elevated LV mass in RASopathy patients is mainly due to cardiomyocyte hyperplasia. [ABSTRACT FROM AUTHOR]

Background: Cardiomyopathies (CMs) are a heterogeneous and severe group of diseases that shows a highly variable cardiac phenotype and an incidence of app. 1/100.000. Genetic screening of family members is not yet performed routinely. Patients and methods: Three families with dilated cardiomyopathy (DCM) and pathogenic variants in the troponin T2, Cardiac Type (TNNT2) gene were included. Pedigrees and clinical data of the patients were collected. The reported variants in the TNNT2 gene showed a high penetrance and a poor outcome, with 8 of 16 patients dying or receiving heart transplantation. The age of onset varied from the neonatal period to the age of 52. Acute heart failure and severe decompensation developed within a short period in some patients. Conclusion: Family screening of patients with DCM improves risk assessment, especially for individuals who are currently asymptomatic. Screening contributes to improved treatment by enabling practitioners to set appropriate control intervals and quickly begin interventional measures, such as heart failure medication or, in selected cases, pulmonary artery banding. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Dilated cardiomyopathy (DCM) is a leading cause of death in children with heart failure. The outcome of pediatric heart failure treatment is inconsistent, and large cohort studies are lacking. Progress may be achieved through personalized therapy that takes age- and disease-related pathophysiology, pathology, and molecular fingerprints into account. We present single nuclei RNA sequencing from pediatric patients with DCM as the next step in identifying cellular signatures.Methods: We performed single nuclei RNA sequencing with heart tissues from 6 children with DCM with an age of 0.5, 0.75, 5, 6, 12, and 13 years. Unsupervised clustering of 18 211 nuclei led to the identification of 14 distinct clusters with 6 major cell types.Results: The number of nuclei in fibroblast clusters increased with age in patients with DCM, a finding that was confirmed by histological analysis and was consistent with an age-related increase in cardiac fibrosis quantified by cardiac magnetic resonance imaging. Fibroblasts of patients with DCM >6 years of age showed a profoundly altered gene expression pattern with enrichment of genes encoding fibrillary collagens, modulation of proteoglycans, switch in thrombospondin isoforms, and signatures of fibroblast activation. In addition, a population of cardiomyocytes with a high proregenerative profile was identified in infant patients with DCM but was absent in children >6 years of age. This cluster showed high expression of cell cycle activators such as cyclin D family members, increased glycolytic metabolism and antioxidative genes, and alterations in ß-adrenergic signaling genes.Conclusions: Novel insights into the cellular transcriptomes of hearts from pediatric patients with DCM provide remarkable age-dependent changes in the expression patterns of fibroblast and cardiomyocyte genes with less fibrotic but enriched proregenerative signatures in infants. [ABSTRACT FROM AUTHOR]

Children with CHD, especially heart-transplanted patients, are predisposed to have caries lesions, gingivitis and other oral findings like gingival hyperplasia. The aim of the study was the implementation of a specific oral hygiene program in these patients and its effect on the improvement of oral health, especially gingival overgrowth. For this, we used a newly developed systematic GHI to evaluate and describe this gingival alteration. Thirty-three children, aged 6 to 15 years with cardiac transplants (9 girls, 24 boys), were examined and introduced into a specific oral hygiene program. Each child showed evidence of gingival hyperplasia. They were randomly divided into three groups with the following oral care measurements: Group ZZ tooth brushing, Group ZZS tooth brushing and mouth rinsing, Group ZZSS tooth brushing, mouth rinsing and the use of an additional single and sulcus toothbrush. A significant decline of all oral health parameters could be proven in all groups. Gingival hyperplasia (GHI) improved as well as plaque accumulation (QHI). The children who used in addition to toothbrushing rinsing solutions and/or additional miniature toothbrushes showed better parameters of the gingival hygiene indexes from the baseline examination until the end of the study. The results show that any infant with cardiac transplant has to be introduced into an individualized oral hygiene program underlining the need of comprehensive dental care in cooperation with pediatric cardiology. [ABSTRACT FROM AUTHOR]

Single ventricle (SV) patients with a Fontan circulation are at risk for functional deterioration. The aim of this study was to assess longitudinal Fontan hemodynamics using serial cardiovascular magnetic resonance (CMR) data and to study the impact of aortopulmonary collateral (APC) flow and type of SV morphology. Forty-one Fontan patients (age at first CMR 13.4 ± 6.0 years) with two CMR examinations within a time interval of at least 4 years (follow-up 5.3 ± 0.9 years) were included. The protocol consisted of short-axis cine volumetry and 2-dimensional blood flow measurements in the inferior vena cava (IVC), superior vena cava (SVC) and ascending aorta (Ao). APC flow was calculated as Ao – (SVC + IVC). Myocardial strain/strain rate was assessed using feature tracking technique. SV end-diastolic volume (p = 0.14) and ejection fraction (p = 0.70) remained constant. No significant changes in CMR derived myocardial strain/strain rate values were observed. Ao flow decreased (p = 0.01), IVC flow remained unchanged (p = 0.52), while SVC flow (p = 0.003) and APC flow (p = 0.006) decreased significantly. Patients with a systemic right ventricle (RV) showed unchanged APC flow and a further increase in SV size over time compared to patients with a systemic left ventricle. Longitudinal CMR data in a cohort of clinically stable Fontan patients revealed no significant changes in SV dimensions and myocardial performance while APC flow decreased spontaneously. Patients with a systemic RV seem to be at risk for permanent SV volume overload through APCs and might therefore benefit from consequent interventional APC embolization. • In a clinically stable Fontan cohort SV size and function remained unchanged after 4-year follow-up. • APC flow decreased spontaneously in the entire study population. • The group with a systemic RV showed unchanged APC flow and progressive SV dilatation. • Systemic RV patients may therefore benefit from consequent interventional APC embolization. [ABSTRACT FROM AUTHOR]

Objective To assess feasibility, safety and effectiveness of right ventricular outflow tract (RVOT) stenting in symptomatic young infants. Methods Multicentre evaluation of 35 patients intended to undergo RVOT stenting in 11 pediatric cardiac centres from 2009 to August 2011. Results Median age and weight at the time of first stent implantation were 8 weeks and 3.3 kg, with 40% of patients <3 kg. A total of 19 patients had suffered from hypoxemic spells, 8 patients were ventilated, 6 on inotropic support and 5 on prostaglandin infusion. Severe concomitant malformations were present in 11 patients, and acute infections in 2. Stenting of the RVOT was successfully performed in 33 patients, improving oxygen saturation from a median of 77 to 90% 2 days after intervention. Besides the 2 patients in whom RVOT stenting was not successful for technical reasons, there were no procedural complications. In 17 of 33 patients, 1-3 reinterventions were performed during follow-up, less than half of those were reinterventions in the RVOT. A total of 27 patients have undergone successful surgical repair 4-162 (median 19.5) weeks after initial RVOT stent implantation, 2 patients are still waiting. There were no perioperative deaths. Conclusions Stenting of the RVOT provides a safe and effective management strategy for initial palliation in symptomatic young infants, including those patients not suitable or at higher risk for surgical therapy. (J Interven Cardiol 2015;28:279-287) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The surgical creation of a Potts shunt has been reported in children with suprasystemic idiopathic pulmonary artery (PA) hypertension (IPAH) refractory to any medical therapy. This surgical approach allows acute decompression of the right ventricle (RV) and thereby avoids ventricular failure. We present 4 newborns and infants with different causes of pulmonary hypertension (PH) in whom interventional stenting of the patent ductus arteriosus (PDA) was used to create a “functional” Potts shunt. Methods: Suprasystemic PH was diagnosed by cardiac catheterization in 2 newborns with complex left heart obstructive lesions, a patient with persistent PH of the newborn (PPHN), and an infant with IPAH and was accompanied by RV dilation and imminent RV failure. Results: Stenting of the PDA was performed uneventfully during cardiac catheterization in all patients and led to stabilization of clinical symptoms. The 2 patients with complex cardiac lesions subsequently underwent successful biventricular repair. In the PPHN patient, the stented PDA was closed interventionally when PA pressures dropped and a significant left-to-right shunt occurred. PA pressures in the patient with IPAH remained high while the stented PDA still served as RV decompression in avoidance of lung transplantation. Conclusions: Newborns and infants with suprasystemic PH of varying etiologies may benefit from the creation of a functional Potts shunt by stenting the PDA. This strategy should be considered in patients with suprasystemic IPAH or PPHN as a temporary or permanent therapy when a PDA can be identified at cardiac catheterization. It may also be beneficial in patients with PH due to left heart obstructions by serving as a bridge to further corrective surgery. [Copyright &y& Elsevier]

Background In patients with anomalous left coronary artery from the pulmonary artery (ALCAPA) left ventricular (LV) dilatation and dysfunction evolves due to diminished myocardial perfusion caused by coronary steal phenomenon. Using late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) imaging, myocardial scarring has been shown in ALCAPA patients late after repair, however the incidence of scarring before surgery and its impact on postoperative course after surgical repair remained unknown. Methods 8 ALCAPA-patients (mean age 10.0 ± 5.8 months) underwent CMR before and early after (mean 4.9 ± 2.5 months) coronary reimplantation procedures. CMR included functional analysis and LGE for detection of myocardial scars. Results LV dilatation (mean LVEDVI 171 ± 94 ml/m2) and dysfunction (mean LV-EF 22 ± 10 %) was present in all patients and improved significantly after surgery (mean LVEDV 68 ± 42 ml/m2, p = 0.02; mean LV-EF 58 ± 19 %, p < 0.001). Preoperative CMR revealed myocardial scarring in 2 of the 8 patients and did not predict postoperative course. At follow-up CMR, one LGE-positive patient showed delayed recovery of LV function while myocardial scarring was still present in both patients. In two patients new-onset transmural scarring was found, although functional recovery after operation was sufficient. One of them showed a stenosis of the left coronary artery and required resurgery. Conclusions Despite diminished myocardial perfusion and severely compromised LV function, myocardial scarring was preoperatively only infrequently present. Improvement of myocardial function was independent of new-onset scarring while the impact of preoperative scarring still needs to be defined. [ABSTRACT FROM AUTHOR]

Background: Dilated cardiomyopathy (DCM) in childhood has a considerable morbidity and mortality and high incidence of heart transplantation. Pulmonary artery banding (PAB) has been proposed in patients with corrected transposition of the great arteries to retrain the sub-pulmonic left ventricle (LV) and to improve a failing sub-aortic right ventricle. We evaluated the short-term and medium-term effects of PAB in young patients with LVDCM. Methods: A retrospective single-center observational study was performed to evaluate the possible benefits of a dilatable surgical PAB in infants and young children with LVDCM. Results: Reported are 12 patients (10 infants, 2 toddlers) with LVDCM referred for heart transplant who received a surgical PAB. There were no hospital deaths. Clinical functional status improved in all patients. The pressure gradient across the PAB increased within 20 days from 28 ± 7 to 43 ± 15 mm Hg. The LV ejection fraction increased from 14.5% ± 5% pre-PAB to 27% ± 13% at hospital discharge and to 47% ± 10% at 3 to 6 months. The LV end-diastolic diameter (z-score) decreased (p > 0.001) from 46 ± 6.1 (+7.0 ± 1.3) to 35 ± 15 mm (+3.0 ± 1.3) after 3 to 6 months and to 34 ± 15 mm (+1.3 ± 1.14) after a median age of 2 years (maximum 6.6 years), respectively. Plasma B-type natriuretic peptide levels decreased from 3431 ± 2610 to 288 ± 321 pg/ml at discharge and to 102 ± 96 pg/ml 22 months later. Eight children were subsequently de-banded by transcatheter technique and 6 of them are currently at Ross Heart Failure Classification for Children class I. Two patients, both with non-compaction DCM, deteriorated at 5 and 6 months after PAB debanding and finally died. Conclusion: In young children with LVDCM and still-preserved right ventricular function, PAB led to an improvement of LV and mitral valve function by ventricular interaction. [ABSTRACT FROM AUTHOR]

Preservation of the pulmonary valve, even at the expense of a mild residual stenosis, is the current surgical policy for the management of patients with tetralogy of Fallot (TOF). This study aimed to assess the long-term effect of a residual right ventricular outflow tract obstruction (RVOTO) on RV dimension and function. This study prospectively assessed 53 children (mean age, 13.4 ± 6.4 years) after repair of TOF using cardiovascular magnetic resonance imaging. Residual RVOTO on echocardiography was defined as a peak systolic RVOT gradient of 25 mmHg or higher. Patients with RVOTO ( n = 29) had significantly less pulmonary regurgitation (25.2 ± 10.6 %) than patients without RVOTO (30.8 ± 9.3 %; p = 0.05) ( n = 24). Compared with patients who had no RVOTO, children with RVOTO had significantly smaller RV end-diastolic volume (94.0 ± 2.6 vs 104.0 ± 20.7 ml/m; p < 0.05) and end-systolic volume (42.9 ± 20.0 vs 48.9 ± 13.2 ml/m; p < 0.05), whereas RV ejection fraction did not differ significantly between the two groups (55.5 ± 8.4 vs 54.0 ± 6.6 %). Restrictive physiology, assessed by late diastolic forward flow in the main pulmonary artery, was equally distributed within the two groups (31 vs 25 %; nonsignificant difference). According to the study data, residual RVOTO after repair of TOF does not affect RV function, whereas RV dimensions and the degree of pulmonary regurgitation are more favorable in the long-term follow-up evaluation of those patients. These results confirm the beneficial effects of the current strategy for repair of TOF. [ABSTRACT FROM AUTHOR]

Objectives The purpose of our study was to assess pulmonary endothelial function by vasodilator response to acetylcholine (Ach) administered in segmental pulmonary arteries in children with idiopathic pulmonary arterial hypertension (IPAH). We hypothesized that there was a relationship among pulmonary endothelial response to Ach, severity of the disease, and clinical outcome. Background IPAH may be associated with pulmonary endothelial dysfunction; however, data regarding the impact of endothelial dysfunction on severity and prognosis of this disease are limited. Methods Forty-three children and adolescents (mean age: 10.4 ± 5.5 years) with IPAH were included in the study. Changes in pulmonary blood flow in response to Ach were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. Results Mean PFR of all patients was 1.58 ± 0.67. Mean follow-up after catheterization was 55.7 ± 41.9 months. Freedom from serious cardiovascular events (lung transplantation or death) was 83% after 2 years, 76% after 3 years, and 57% after 5 years. PFR was related significantly to World Health Organization functional class. Receiver-operating characteristic curves revealed a PFR of 1.4 as the best cutoff value. Kaplan-Meier analysis demonstrated that a PFR of <1.4 was highly predictive for cardiovascular events (log-rank [Mantel Cox] chi-square: 12.49, p < 0.0001). Conclusions Our study demonstrates a strong relationship between pulmonary endothelial response to Ach and prognosis of children with IPAH. As an adjunct to the usual testing protocol, this method provides additional information for therapeutic guidance. [ABSTRACT FROM AUTHOR]

Ductal stenting for pulmonary blood supply in newborns with cyanotic congenital heart disease (CHD) might be a low risk and safe alternative to the surgical aorto-to-pulmonary artery (AP) shunt in dual-source lung perfusion. Ductal stenting in truly duct-dependent pulmonary circulation has not been evaluated. Prospective interventional and clinical follow-up trial. Ductal stenting based on variable access sites, a 2-wire technique when crossing a tortuous ductus, and use of premounted coronary stents. Primary outcome measures were procedural success and complication rates presented as early and mid-term results. From 2003-2009, 58 duct-dependent newborns underwent ductal stenting; 27 of them were truly duct dependent, 20 had pulmonary atresia (PA)/ventricular septum defect or complex CHD, 4 had PA/intact ventricular septum, 2 had PA with Ebstein anomaly, and 1 had PA with tricuspid atresia. Ductal stenting was performed without procedure-related mortality; 3 of 27 required an acute surgical AP-shunt (stent migration in 1, acute duct obstruction in 2). During mid-term follow-up, 4 of 24 needed an AP-shunt and two others stent redilation. Three patients died prior to follow-up surgery (1 unexpectedly at home and 2 due to syndromatic disease). Fifteen patients received staged univentricular palliation, 8 had a biventricular repair, and 1 is awaiting follow-up operation. Ductal stenting is a feasible, safe, and effective palliation in newborns with truly duct-dependent pulmonary circulation irrespective of duct morphology. Vasucular access from various locations is important for technical success rate. Ductal stenting is a minimally invasive procedure to achieve adequate pulmonary artery growth for subsequent palliative or corrective surgery. (J Interven Cardiol 2010;23:581-588) [ABSTRACT FROM AUTHOR]

Novel surgical strategies have dramatically improved the initial outcome of newborns with hypoplastic left heart syndrome. However, the single systemic right ventricle remains a major challenge, with limited effectiveness of pharmacologic therapy. The present case documents that the intracoronary administration of autologous bone marrow-derived progenitor cells is technically feasible in a critically ill infant with hypoplastic left heart syndrome and severe heart failure after a hybrid comprehensive stage II procedure. Cell therapy might represent an option before heart transplantation in children with single ventricle physiology presenting with severe heart failure. [Copyright &y& Elsevier]

During neonatal cardiac development, the heart changes its substrate preference from glucose to fatty acids. The aim of this study was to investigate the changes in mRNA expression levels of genes involved in the control of cardiac fatty acid metabolism in the transition from neonatal to adult life. [ABSTRACT FROM AUTHOR]

Clinical data using the noncontact mapping system (Ensite 3000) suggest that characteristics of the reconstructed unipolar electrograms may predict the origin of electrical activation within the atrial and ventricular walls (endocardial vs myocardial vs epicardial origin). Experimental data are lacking. In ten open-chest pigs (mean body weight 62 kg) cardiac pacing was performed at a cycle length of 600 ms with a pulse width of 2 ms and twice diastolic threshold from the endo-, the myo-, and the epicardium, respectively. Pacing was undertaken at three right atrial and three left ventricular sites, and cardiac activation was recorded with the Ensite system. Reconstructed unipolar electrograms at the location of earliest endocardial activation assessed by color coded isopotential maps were analyzed systematically for differences in morphology. The positive predictive value of atrial electrograms exhibiting an initial R wave during pacing for a subendocardial origin (i.e., myocardial or epicardial) was 0.96. The negative predictive value was 0.48. Electrograms generated during myocardial pacing exhibited increased maximal negative voltage and maximal dV/dt (-3 ± 1.8 mV, -798 ± 860 mV/ms , respectively) than the electrograms obtained during endocardial (-2 ± 1 mV, -377 ± 251 mV/ms , respectively) and epicardial pacing (-2.1 ± 0.7 mV, -440 ± 401 mV/ms , respectively, P < 0.01 for both parameters). During pacing at the left ventricular wall, occurrence of an initial R wave did not differ significantly between electrograms reconstructed during endocardial and subendocardial pacing. All other characteristics of the unipolar ventricular electrograms analyzed, except latency, did not differ significantly when compared to stimulation depth. Morphological characteristics of unipolar electrograms generated by the noncontact mapping system during pacing of the atrium allowed for discrimination of an endocardial versus a subendocardial origin of activation. At the ventricular level, characteristics of unipolar electrograms did not predict the origin of cardiac activation in this experimental setting. (PACE 2003; 26:1970–1978) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Diet composition impacts metabolic and cardiovascular health with high caloric diets contributing to obesity related disorders. Dietary interventions such as caloric restriction exert beneficial effects in the cardiovascular system, but alteration of which specific nutrient is responsible is less clear. This study investigates the effects of a low protein diet (LPD) on morphology, tissue composition and function of the neonatal and adult mouse heart. Mice were subjected to LPD (8.8% protein) or standard protein diet (SPD, 22% protein) throughout intrauterine and postnatal life. At birth LPD female but not male offspring exhibit reduced body weight whereas heart weight was unchanged in both sexes. Cardiomyocyte cross sectional area was increased in newborn LPD females compared to SPD, whereas proliferation, cellular tissue composition and vascularization were unaffected. Adult female mice on LPD exhibit reduced body weight but normal heart weight compared to SPD controls. Echocardiography revealed normal left ventricular contractility in LPD animals. Histology showed reduced interstitial fibrosis, lower cardiomyocyte volume and elevated numbers of cardiomyocyte and non-myocyte nuclei per tissue area in adult LPD versus SPD myocardium. Furthermore, capillary density was increased in LPD hearts. In conclusion, pre- and postnatal dietary protein restriction in mice causes a potentially beneficial myocardial remodeling. [ABSTRACT FROM AUTHOR]

Background:Aortopulmonary collaterals (APCs) are frequently found in patients with a single-ventricle (SV) circulation. However, knowledge about the clinical significance of the systemic-to-pulmonary shunt flow in patients after the modified Fontan procedure and its potential causes is limited. Accordingly, the aim of our study was to detect and quantify APC flow using cardiovascular magnetic resonance (CMR) and assess its impact on SV volume and function as well as to evaluate the role of the size of the pulmonary arteries in regard to the development of APCs. Methods:60 patients (mean age 13.3 ± 6.8 years) after the Fontan procedure without patent tunnel fenestration underwent CMR as part of their routine clinical assessment that included ventricular functional analysis and flow measurements in the inferior vena cava (IVC), superior vena cava (SVC) and ascending aorta (Ao). APC flow was quantified using the systemic flow estimator: (Ao) - (IVC + SVC). Pulmonary artery index (Nakata index) was calculated as RPA + LPA area/body surface area using contrast enhanced MR angiography. The patient cohort was divided into two groups according to the median APC flow: group 1 < 0.495 l/min/m2 and group 2 > 0.495 l/min/m2. Results:Group 1 patients had significant smaller SV enddiastolic (71 ± 16 vs 87 ± 25 ml/m2; p=0.004) and endsystolic volumes (29 ± 11 vs 40 ± 21 ml/m2; p=0.02) whereas ejection fraction (59 ± 9 vs 56 ± 13%; p=0.38) differed not significantly. Interestingly, pulmonary artery size showed a significant inverse correlation with APC flow (r=-0.50, p=0.002). Conclusions:Volume load due to APC flow in Fontan patients affected SV dimensions, but did not result in an impairment of SV function. APC flow was related to small pulmonary artery size, suggesting that small pulmonary arteries represent a potential stimulus for the development of APCs. [ABSTRACT FROM AUTHOR]