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Background Right ventricular outflow tract (RVOT) stenosis after repair of tetralogy of Fallot has been linked with favorable right ventricular remodeling but adverse outcomes. The aim of our study was to assess the hemodynamic impact and prognostic relevance of right ventricular pressure load in this population. Methods and Results A total of 296 patients with repaired tetralogy of Fallot (mean age, 17.8±7.9 years) were included in a prospective cardiovascular magnetic resonance multicenter study. Myocardial strain was quantified by feature tracking technique at study entry. Follow‐up, including the need for pulmonary valve replacement, was assessed. The combined end point consisted of ventricular tachycardia and cardiac death. A higher echocardiographic RVOT peak gradient was significantly associated with smaller right ventricular volumes and less pulmonary regurgitation, but lower biventricular longitudinal strain. During a follow‐up of 10.1 (0.1–12.9) years, the primary end point was reached in 19 of 296 patients (cardiac death, n=6; sustained ventricular tachycardia, n=2; and nonsustained ventricular tachycardia, n=11). A higher RVOT gradient was associated with the combined outcome (hazard ratio [HR], 1.03; 95% CI, 1.00–1.06; P =0.026), and a cutoff gradient of ≥25 mm Hg was predictive for cardiovascular events (HR, 3.69; 95% CI, 1.47–9.27; P =0.005). In patients with pulmonary regurgitation ≥25%, a mild residual RVOT gradient (15–30 mm Hg) was not associated with a lower risk for pulmonary valve replacement. Conclusions Higher RVOT gradients were associated with less pulmonary regurgitation and smaller right ventricular dimensions but were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not protect from pulmonary valve replacement. These results may have implications for the indication for RVOT reintervention in this population.

The truncus arteriosus communis is a very complex congenital cardiac malformation occurring in less than 1% of all congenital heart disease patients. Early repair remains one of the most challenging procedures in congenital cardiac surgery. Due to improvement in surgical reconstruction strategies over the past years, there is an acceptable short and long-term survival for those patients. However, each new case represents a “high mountain to climb” in ambition to achieve physiological repair with acceptable hemodynamic and a good long-term survival. We therefore present a very special case with anomalous origin and intramural course of the right coronary artery.

Chylothorax occurs in 2.8-5% of infants after cardiac surgery and can increase morbidity and mortality. First-line conservative treatment consists of a chest tube drainage and a fat-free and medium-chain triglyceride (MCT)-enriched diet. This typically leads to a discontinuity of breast milk feeding due to high content of long-chain triglycerides within the breast milk. Modified breast milk with low fat content (LFBM) could provide numerous benefits like immunological properties of breast milk even for patients with chylothorax. This study was conducted at Herzzentrum Leipzig comparing clinical and growth outcomes between infants with chylothorax after surgery for congenital heart disease treated with LFBM (n = 13) versus MCT-Formula (n = 10). LFBM was prepared by centrifugation of native breast milk added with MCT-oil and fortifier. There were no differences in volume and duration of chest tube drainage between LFBM and MCT-formula treatment groups. Furthermore, no statistically significant differences with regard to weight and length gains could be observed between both feeding groups. LFBM is an efficient and unharmful treatment for chylothorax following cardiac surgery in young children.

OBJECTIVES We evaluated 4384 procedures performed between 1957 and 2018, collected in the National Register for Congenital Heart Defects, conducted on 997 patients with 1823 pulmonary valve replacements (PVRs), including 226 implanted via catheter [transcatheter valve (TCV)]. Main study targets are as follows: TCV benefit, valve type durability, decade-wise treatment changes and procedure frequencies over the lifetime of a PVR patient. METHODS We studied TCV impact on surgical valve replacement (via Kaplan–Meier); pulmonary valve type-specific performance (Kaplan–Meier and Cox regressions with age group as stratification or ordinary variable); procedure interval changes over the decades (Kaplan–Meier); procedure load, i.e. frequency of any procedure/surgical PVR/interventional or surgical PVR by patient age (multistate analyses). RESULTS TCV performance was equivalent to surgical PVRs and extended durability significantly. Homografts were most durable; Contegras lasted comparably less in older; and Hancock devices lasted less in younger patients. Matrix P-valves showed poorer performance. Age group stratification improves the precision of valve-specific explantation hazard estimations. The current median interval between procedures is 2.6 years; it became significantly shorter in most age groups below 40 years. At 30 years, 80% of patients had undergone ≥3 procedures, 20% ≥3 surgical PVRs and 42% ≥3 surgical or interventional PVRs. CONCLUSIONS TCVs doubled freedom from explantation of conventional valves. Homografts’ age group-specific explantation hazard ratio was lowest; Matrix P’s hazard ratio was highest. Age-stratified Cox regressions improve the precision of prosthesis durability evaluations. The median time between procedures for PVR patients shortened significantly to 2.6 years. At 30 years, 42% had ≥3 PVRs.

Introduction:Cardiopulmonary bypass surgery is accompanied by an inflammatory response and pulmonary dysfunction that renders patients vulnerable to postoperative complications. The majority of studies investigating the inflammatory response in cardiopulmonary bypass focus on cytokine measurements. This study investigated the early response of peripheral blood cell types and early changes in lung tissue in on-pump versus off-pump cardiopulmonary bypass surgery.Methods:Landrace pigs were assigned to the following groups (n = 6 per group): 1. off-pump cardiopulmonary bypass, 2. conventional cardiopulmonary bypass, 3. heparin-coated cardiopulmonary bypass, 4. surface-reduced cardiopulmonary bypass, and 5. surface-reduced cardiopulmonary bypass plus lung perfusion. Surgery was performed under mild hyperthermia (32°C), with 90-minute ischemia and 180-minute reperfusion. Histological and flow cytometric analyses were performed.Results:Lung water content increased during reperfusion in heparin-coated (84.63 ± 2.99%) compared to conventional cardiopulmonary bypass (76.33 ± 4.56%, p = 0.04). Alveolar septal thickness increased during ischemia at heparin-coated (p +CD4+(p = 0.03) and CD3+CD8+(p = 0.01) T cells compared to an uncoated device. Natural killer and mature B lymphocytes decreased at conventional and surface-reduced cardiopulmonary bypass plus lung perfusion. Activated granulocytes and macrophages increased at conventional cardiopulmonary bypass and heparin-coated cardiopulmonary bypass.Conclusion:Off-pump cardiopulmonary bypass induces less immunological response and lung injury than on-pump surgery. The reduction of cardiopulmonary bypass surface reduces the inflammatory immune response induced by cardiopulmonary bypass. Lung perfusion of surface-reduced cardiopulmonary bypass diminished the extravasation caused by surface reduction of the cardiopulmonary bypass.

Myocardial bridging is a congenital coronary artery anomaly in which the coronary artery has a partly “tunnelled” intramyocardial course. This tunnelling leads to compression of the affected vessel segment during ventricular systole. It is considered to be a benign variation of the norm in about 25% of the population caused by an aberrancy of embryologic coronary development. The bridging is also thought to cause severe cardiac conditions in a few of those affected. The series of six young patients presented here is the largest series so far to report on symptomatic myocardial bridging in children with different underlying heart diseases. All patients recently presented to our centre with signs of myocardial ischaemia. They subsequently underwent coronary angiography, which revealed myocardial bridging of the ramus interventricularis anterior. In all patients, therapy with β blockers was started to reduce heart rate and myocardial contractility. β Blocker treatment was also given in order to prolong diastole and improve coronary artery blood flow. Two patients underwent surgical exposure of the involved coronary segment: a 2-year-old boy because of recurrent, severe myocardial ischaemia in combination with a reduction of general health, changes in ST-segments, and the presence of a dilative cardiomyopathy; and a 13-year-old girl because of evidence of myocardial ischaemia during exercise testing after surviving sudden cardiac death. Surgery was successful and recovery was complete and uneventful. The presented series shows that myocardial bridging can be symptomatic and may require urgent treatment and even surgical intervention in early childhood in rare cases.

Background Endomyocardial biopsies (EMB) are the gold standard for the diagnosis of myocarditis in children and adults. The existing WHO/ISFC criteria for lymphocytic cell infiltrates by are based on the myocardium of adults. The aim of this study was to present a paediatric control cohort for the evaluation of inflammation in EMB of children. Methods In this study endomyocardial tissue from 62 children under 4 years of age was investigated, being collected during a planned open heart surgery with routine resection from ventricular site. Patients had no history of infection or myocardial inflammation. The heart tissue was formalin fixed and embedded in paraffin. Four μm thick tissue sections were stained with haematoxylin and eosin, Masson's trichrome, and Giemsa. Immunohistochemical stainings included quantitative evaluation of CD3+ T cells, CD20+ B cells, CD68+ macrophages and MHCII expression. Results The myocardium was obtained in 96.8% (n = 60) of the cases from the right and in 3.2% (n = 2) from the left ventricle. The median age (interquartile range) at biopsy was 0.5 years (0.3–0.9), 66.1% male. Within this cohort, a median of 2.5/mm2 (1.0–4.0) CD3+ T cells, 0.5/mm2 (0.0–0.6) CD20+ B cells and 4.0/mm2 (2.5–6.0) CD68+ macrophages were detected. The MHC II grade was 0 in 71.0% (n = 44) and 1 in 29.0% (n = 18). Conclusion This is the first paediatric control cohort being relevant for the correct interpretation of inflammatory heart diseases in EMB. The lymphocytic cell numbers in children needing congenital heart surgery without myocardial inflammation are below the existing values in adults.

Lung dysfunction constitutes a severe complication after major cardiac surgery with cardiopulmonary bypass (CPB), substantially contributing to postoperative morbidity and mortality. The current possibilities of preventive and therapeutic interventions, however, remain insufficient. We, therefore, investigated the effects of intraoperative application of the antioxidant and anti-inflammatory green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on CPB-associated lung injury.Thirty piglets (8-15 kg) were divided into four groups: sham-operated and saline-treated control group (n = 7); sham-operated and EGCG-treated control group (EGCG-control group; n = 7); CPB group (n = 10); and CPB + EGCG group (n = 6). The CPB groups underwent 120 min of CPB followed by 90 min of recovery time. In the CPB + EGCG group, EGCG (10 mg/kg body weight) was administered intravenously before and after CPB. Hemodynamic monitoring, blood gas analysis, hematoxylin-eosin staining, and immunohistochemistry of lung tissue were performed.Histologic examination revealed thickening of the alveolar wall and enhanced alveolar neutrophil infiltration in the CPB group (P0.05) compared with those in the control group, which was prevented by EGCG (P0.05). In the CPB group, higher formation of poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor was detected in comparison with those in the control group (P0.001), which were both reduced in the CPB + EGCG group (P0.001). Compared with the control group, the EGCG-control group showed thickening of the alveolar wall and increased neutrophil infiltration (P0.05).CPB leads to lung edema, pulmonary neutrophil infiltration, and presumably initiation of poly(ADP-ribose) polymerase-dependent cell death signaling in the lung. EGCG appears to attenuate CPB-associated lung injury, suggesting that this may provide a novel pharmacologic approach.

Introduction Dilatation of the ascending aorta is a common finding in Tetralogy of fallot (TOF). We sought to provide aortic dimensions in children and adolescents after corrected TOF obtained by contrast-enhanced cardiac-magnetic-resonance angiography (CE-CMRA) that could serve as reference values. Materials and methods We enrolled 101 children and adolescents (56 male) with a median age of 10.9 years. All patients underwent CE-CMRA imaging using a 3-dimensional spoiled gradient-echo-sequence. Aortic diameters were measured at the level of the aortic valve (AV), aortic sinus (AS), sino-tubular junction (STJ) and the ascending aorta (AA) and compared with normal values obtained from literature. Sex-specific aortic dimensions are given as percentile curves as well as z scores. Furthermore CMR volumetric and functional parameters as well as clinical and anamnestic data were analyzed to identify parameters that are associated with aortic dilatation. Results Diameters for aortic size for males were 3.6 + 16.6*BSA0.5 at the AV level, 7.0 + 19.5*BSA0.5 at the AS level, 7.0 + 14.4*BSA0.5 at the STJ level and 7.3 + 15.5*BSA0.5 at the AA level. Diameters for females were 5.8 + 14.1*BSA0.5 at the AV level, 7.2 + 17.6*BSA0.5 at the AS level, 5.2 + 15.4*BSA0.5 at the STJ level and 2.0 + 17.8*BSA0.5 at the AA level. All diameters in TOF patients were larger compared with normal values. The postoperative interval and age at examination were the only parameters associated with aortic size at all measured levels. Conclusion We provide CE-CMRA data of aortic dimensions in children and adolescents after correction of TOF. Our data might be useful for an estimation of the “normal” aortic size in this patient cohort and can serve as a basis for future longitudinal studies adding prognostic data.

Cardiopulmonary bypass (CPB) often is required for the operative correction of congenital heart defects in small infants. Unfortunately, CPB is associated with injury of inner organs such as the brain, kidney, lung, and liver. Renal failure and increase in liver enzymes are typical side effects observed after CPB. Here, we investigate whether organ protection of the kidney and liver can be achieved with the application of minocycline, which is known-besides its anti-infective effects-to act as a poly-ADP-ribose-polymerase inhibitor. Twenty-nine 4-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into four groups: control group (n = 8), CPB group (n = 9), minocycline-control group (n = 6), and the minocycline-CPB group (n = 6). CPB groups were thoracotomized and underwent CPB for 120 min (cross-clamp, 90 min; reperfusion, 30 min) followed by a 90-min recovery time. The control groups also were thoracotomized but not connected to CPB. The minocycline group received 4 mg/kg minocycline before and 2 mg/kg after CPB. In the kidneys, CPB histologically resulted in widening of Bowman's capsule, and-mainly in tubules-formation of poly-ADP-ribose, nitrosylation of tyrosine-residues, nuclear translocation of hypoxia-induced factor HIF-1α, and of apoptosis-inducing factor (AIF). In addition, we found significantly less ATP in the kidney and significantly increased plasma urea and creatinine. Similar but gradually attenuated changes were found in the liver together with significantly elevated de-Ritis coefficient. These changes in the kidney and liver were significantly diminished by minocycline (except AIF in the liver which was similar in all groups). In conclusion, CPB causes damage in the kidney and-to a lower degree-in the liver, which can be attenuated by minocycline.

We describe a rescue operation in a neonate with a large left ventricular tumor obstructing the left ventricular outflow tract. Surgical resection was performed through an aortotomy and transseptal approach. We excised the main part of the tumor, which was obstructing the outflow tract, leaving a portion that was strongly attached to posterior wall of the left ventricle and mitral valve annulus, which was not feasible to remove. Histological examination showed a rhabdomyoma with benign features. The girl was doing well after 3 months, with no residual tumor growth and no signs of obstruction of the left ventricular outflow tract.

Objectives Somatic development is impaired in children with congenital heart defects (CHDs), and head circumference seems to be a strong predictor of neurodevelopmental prognosis. The aim of this study was to generate up-to-date reference values for the somatic development (head circumference, body weight, and length/height) of children with CHDs. Study design Our study population consisted of all patients included in the PAN study (Pravalenz angeborener Herzfehler bei Neugeborenen in Deutschland), which was conducted prospectively over a 3-year study period by the Competence Network for Congenital Heart Defects. All children with mild, moderate, and severe CHDs born in 2006-2009 in Germany were enrolled. For computing of z-scores, only children with the following characteristics were included: appropriate for gestational age, nonsyndromic disease, term or post-term delivery, and no cardiac surgery. Results There were 2818 patients included. New z-scores for the described somatic measures of children with mild, moderate, and severe CHDs were computed. Comparisons with the KiGGS study (Gesundheit von Kindern und Jugendlichen in Deutschland) and the Berlin Longitudinal Study revealed significantly lower measurements for all measures—most notably in children with severe CHDs and/or cardiac surgery. In our cohort, no catch-up growth was seen after cardiac surgery. Conclusion Children with severe CHDs demonstrated the most abnormal pattern in growth, including head circumference before and after cardiac surgery, which is indicative of accompanying brain pathology unrelated to operative injury.

PURPOSE Dilatation of the thoracic aorta is a well-known finding in corrected Tetralogy of Fallot. Complications are rare but can be life-threatening. Standard 1-dimensional (1D) measurements have several limitations. We sought to establish contrast-enhanced magnetic resonance angiography cross-sectional areas of the aorta that could serve as reference values and to identify parameters that are associated with aortic dilatation. MATERIALS AND METHODS We enrolled 101 children and adolescents. The aortic areas were measured at the level of the aortic sinus (AS), the sinotubular junction (STJ), the ascending aorta (AA), the brachiocephalic trunk (TBC), and the descending aorta (DA). Sex-specific aortic dimensions were presented as percentile curves as well as regression equations. Furthermore volumetric and functional parameters as well as clinical data were analyzed to identify parameters that are associated with aortic dilatation. RESULTS Aortic areas (mm) for female subjects were 139+366×body surface area (BSA) for the AS, 134+255×BSA for the STJ, 113+239×BSA for the AA, 88+185×BSA proximal to the TBC, and 2.9+88×BSA for the DA. Aortic areas (mm) for male subjects were 162+403×BSA for the AS, 171+258×BSA for the STJ, 151+233×BSA for the AA, 73+206×BSA proximal to the TBC, and 21+80×BSA for the DA. The postoperative interval and age at examination were parameters associated with aortic size. CONCLUSIONS We provide aortic areas in children and adolescents after correction of Tetralogy of Fallot measured by contrast-enhanced magnetic resonance angiography. Our 2D data may better depict the geometry of enlarged aortae than standard 1D diameters and serve as reference values for evaluating aortic disease in these patients.

A main problem with bioprosthesis used for surgical correction of congenital cardiac malformation is its tendency to shrink and to calcify. Recently, a new material, that is, decellularized bovine pericardium (CardioCel), was introduced in clinics. It was proposed that this new patch material should not calcify and should be particularly suitable for the correction of vascular defects in inborn cardiac diseases. The aim of our chronic minipig study was to evaluate the performance of CardioCel patches implanted in aortic and pulmonary artery position, respectively. Ten minipigs aged 3 months were operated on. A CardioCel patch was implanted in the aorta ascendens and arteria pulmonalis, respectively. Seven minipigs completed the 12 months' follow-up. Angiography of both vessels, measurement of pressure gradients, and histologic evaluation of the implanted patches were carried out. Angiography of both great vessels revealed a good clinical outcome without stenosis. However, histologic examination of the patches showed calcification and neo-formation of hyaline cartilage in both vessel types. Staining of collagen and elastic fibers as well as α-smooth muscle actin demonstrated that the patches did not remodel into an anatomic vascular structure during the 1 year of implantation. In our chronic piglet model, CardioCel patches, when implanted in the ascending aorta and the pulmonary artery, led to calcification and neo-formation of hyaline cartilage in both vessel types 1 year after implantation. The present study indicates that the ideal patch biomaterial for repair of inborn cardiac diseases is still a goal not achieved yet.

Aims Results of catheter based interventional treatment for pulmonary vein stenosis (PVS) following radiofrequency ablation (RFA) for atrial fibrillation remain suboptimal. Surgical repair may represent an alternative therapy, though long-term results have not been thoroughly investigated. Methods and results We retrospectively assessed all patients in our centre undergoing surgical repair for radiofrequency-induced PVS. Data regarding surgical technique, clinical outcome, and rate of pulmonary vein (PV) restenosis were collected and analysed. Between 2004 and 2016, the rate for PVS resulting from RFA for atrial fibrillation in our institution was 0.79% (76/9633). During this period, five male patients with multiple PVS (3 ± 1) underwent surgical repair of a total of 13 symptomatic PVS. Surgery was performed in a standard setting under cardiopulmonary bypass. Stenotic veins were incised longitudinally followed by a patch augmentation plasty using either bovine pericard (n = 7) or polytetrafluoroethylene (PTFE) patches (n = 5). Localization of incision was on the anterior side of the PV only (n = 8) or on both the anterior and posterior sides (n = 4). In one PVS lesion, mechanical dilatation was sufficient. Long-term follow-up after 60 ± 69 months revealed an average restenosis rate of 38%. Restenosis was defined as narrowing >70%. All patients reported clinical improvement of symptoms at follow-up. Conclusion Even in the era of wide circumferential lesions, PVS still occurs. While surgical PV patch plasty represents a valuable treatment option, restenosis remains an issue during follow-up. Nevertheless, surgical repair achieves highly acceptable long-term results for RFA-acquired PVS. Hence, it should be routinely discussed as a therapeutic option in cases with multiple PVS.

Mechanical stretch has been shown to provoke arrhythmia. We wanted to analyze ventricular arrhythmia induced by local left ventricular stretch in order to find out, where arrhythmias originate and whether they can be prevented pharmacologically. Isolated rabbit hearts (Langendorff technique) were submitted to increased left ventricular stretch at the left wall by insertion of an additional intraventricular balloon and adjusting the end-diastolic pressure (EDP) to 25 mmHg for 10 min followed by 20 min recovery at normal EDP of 5–8 mmHg. Activation and repolarization processes were investigated by ventricular 256 electrode epicardial mapping. The hearts were treated during the whole procedure either with vehicle, 0.5 μM flecainide (sodium channel blocker) or 100 μM streptomycin (here used as stretch-activated ion-channel blocker). In addition, we performed a series of experiments, in which we enhanced EDP to 30 mmHg (global stretch instead of local stretch) by inflating the left ventricular pressure balloon (strain, 0.148 ± 0.034). Each series was performed with n = 6. Stretch resulted in local strain of 25 % at the left wall together with a local slowing of the activation process at the left wall, in a change in the activation pattern, and in ventricular arrhythmia. Coronary flow was not affected. Ventricular arrhythmias originated from the border between the stretched area and the non-stretched region. Flecainide and streptomycin reduced the prolongation of the activation process at the stretched left wall and mitigated the difference in total activation time between left and front wall but only partially prevented arrhythmia. In the additional global stretch experiments relative coronary flow and the other parameters remained unchanged, in particular TAT. Thus, in contrast to the local stretch series, there was no difference in the change in TAT between left and front wall. Only rare single ventricular extrasystoles (

Increased body mass index (BMI) is often found to be a risk factor for cardiac disease. However, it is unclear whether BMI also affects the gap junction remodeling process in atrial fibrillation (AF). The aim of the study was to see if BMI can influence the connexin43 (Cx43) distribution in patients with sinus rhythm (SR) and AF.We investigated a total of 51 white Caucasian patients of both gender (mean age: 69 years, 30% diabetes mellitus, ejection fraction [EF] 50%) with SR or AF, with either BMI 27 or ≥ 27 undergoing cardiac surgery for mitral valve repair, aortic valve repair, or coronary heart disease. We obtained human right atrial tissue for immunohistochemistry and investigated the CX43-positive polar and lateral membrane length in the different BMI (BMI 27, BMI ≥ 27) and rhythm groups (SR or AF).In lean SR patients, Cx43 (BMI 27) was found mainly at the cell poles while only 2% of the lateral membrane stained positive for Cx43. In obese SR patients (BMI 27), 6.7 ± 0.7% of the lateral membrane was positive (p 0.05). In AF generally, there was significantly more lateral Cx43 staining, which was significantly enhanced in obese AF patients. In lean AF patients, lateral Cx43 positivity increased to 14 ± 1% (p 0.05), while in BMI 27 AF patients, this was significantly enhanced to 22 ± 2% (p 0.05). The BMI effect was independent from left atrial diameter, EF, and comorbidity.Enhanced BMI is associated with increased remodeling effects of AF on irregular Cx43 distribution.

Aim The aim of this study was to characterize an alternative treatment for dilated cardiomyopathy (DCM) using a novel cardiac biological assist device created from engineered heart tissue (EHT). Methods and results The EHTs were constructed in vitro from matrigel, collagen, and neonatal rat cardiomyocytes as small ring-like spontaneously contracting devices. DCM was induced in 50 rats by 6 weeks doxorubicin treatment (2.5 mg/kg/week). After 38 drug-free days, rats underwent either implantation of EHT (DCM-EHT, n = 13), which was sutured around the ventricles, or sham operation (DCM-Sham, n = 12). Eleven untreated healthy rats served as the control group. Rats were investigated using a Millar catheter for pressure–volume loop recording, and by echocardiography 30 days after operation. Thereafter, the hearts were excised and investigated functionally, histologically, and biochemically. Doxorubicin led to the development of DCM with reduced fractional shortening (FS), reduced dP/dtmax, increased systolic and diastolic LV diameters, and reduced response to dobutamine. In DCM-Sham, these changes were further enhanced, while in DCM-EHT we found improved FS, dP/dtmax, and dobutamine responsiveness. In isolated hearts, electrical multielectrode mapping revealed that EHT was electrically activated synchronously to the recipient heart. Histologically, we found increased vascularization in the EHT and the recipient heart, and EHT vessels connected to the coronary system. Conclusions Implantation of EHT improves LV performance in rats with doxorubicin-induced DCM.

Cardiopulmonary bypass still often is a necessary tool in cardiac surgery in particular in the correction of congenital heart defects in small infants. Nevertheless, among the complications linked to extracorporeal circulation (ECC) with cardiopulmonary bypass (CPB) in both infants and adults one of the most serious problems is renal impairment. Since this might be caused by ischemia/reperfusion injury and accumulation of free radicals, we used (-)-epigallocatechin-3-gallate (EGCG), a derivate from green tea, which is known to possess antioxidant, antiapoptotic and NO-scavenging properties in order to find out whether EGCG may protect the kidney. 23 four-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into three groups: control-group (n=7), ECC-group (n=10), EGCG-group (n=6). The ECC- and EGCG-group were thoracotomized and underwent CPB for 120 min followed by a 90-min recovery-time. The EGCG-group received 10 mg/kg EGCG before and after CPB. Histology revealed that CPB led to widening of Bowman's capsule, and to vacuolization of proximal tubular cells (p

Objectives: Timing of primary repair of tetralogy of Fallot (TOF) remains controversial. We evaluated the long-term outcome of early primary treatment strategy in a patient cohort with TOF less than eight months of age. Methods: A group of 120 patients with TOF less than eight months of age (5 ± 2.4 months) underwent early primary repair of TOF between October 1998 and August 2009. Sixty-one patients received a transanular (TAN) repair, and 59 patients received a right ventricular outflow tract (RVOT) + main pulmonary artery (MPA) double patch repair with concomitant pulmonary valve reconstruction. Result: There was no early or late mortality. The follow-up was 100% completed. There were eight reoperations and eight patients underwent catheter intervention for severe pulmonary valve insufficiency or stenosis, obstruction of right ventricular outflow tract, and stenosis of pulmonary arteries. Actuarial survival was 100% at ten years. At latest follow-up 80 patients were in NYHA Class I without any antiarrhythmic medications. On latest echocardiography, 90 (75%) patients had mild to moderate pulmonary regurgitation, and 10 had a right ventricular outflow tract gradient more than 40 mmHg. Conclusions: These data strongly support the concept of early primary repair of TOF in patients with well developed pulmonary arteries. Early primary repair is associated with an excellent early and late outcomes, an acceptable risk of reoperation and re-intervention, and a low incidence of significant right ventricular dysfunction.

Connexins (Cx) are suggested to play important roles in growth and differentiation. Aim of our study was to investigate the role of endothelial Cx in the angiogenic process. Several parameters of angiogenesis were assessed in 18 h Matrigel in vitro angiogenesis assays with human umbilical vein endothelial cells (HUVEC). Prior to culture on Matrigel cells were treated with nicotine or the gap junction inhibitor palmitoleic acid (PA), or siRNA-knock-down of either Cx37, Cx40 or Cx43 was performed. Changes in Cx expression and their effects on gap-junctional communication were investigated using immunofluorescence microscopy, Western blot and Lucifer Yellow dye transfer. Knock-down of each Cx-isoform significantly reduced the amount of specific Cx protein in HUVEC. Cx-knock-down as well as treatment with PA impaired intercellular communication via gap junctions and diminished significantly the number of capillary branches. Knock-down of Cx43 and Cx40 or treatment with PA reduced complexity pattern in the angiogenesis assay. Nicotine significantly reduced expression of Cx43 and Cx37 as well as average length of capillary branches, number of branches and pattern in the Matrigel assay. We can conclude that connexins are involved in angiogenesis, in particular in branch formation. This can partly explain the changes in angiogenesis seen under nicotine treatment.

Our study aimed to elucidate whether bone marrow stem cell (BMC) treatment might result in a cellular response in cardiomyocytes IN VITRO. Subconfluent neonatal rat cardiomyocyte cultures were cocultured for three days with Vybrant CM-DiI labeled BMC from human sternal bone marrow and underwent immunohistological staining for the proto-oncogene c-Myc and the cell cycle proteins CDK2, CDK4 and ATF-3. β-adrenoceptor density was analyzed using [125I]-iodocyanopindolol (ICYP) histoautoradiography. Quantitative analysis of immunohistochemical images revealed significantly increased expression and upregulation of c-Myc, and its downstream targets ATF-3, CDK2 and CDK4 in neighboring cardiomyocytes to BMC, depending on their distance to the BMC compared to cardiomyocytes far from the BMC. Histoautoradiography revealed a significantly higher β-adrenoceptor density in cardiomyocytes in the immediate vicinity to the BMC. With increasing distance to the BMC, β-adrenoceptor density in cardiomyocytes declined. Thus, a small number of BMC can affect a larger number of cardiomyocytes by activating an intracellular signaling cascade and enhancing β-adrenoceptor density.

Pulse oximetry screening (POS) has been proposed as an effective, noninvasive, inexpensive tool allowing earlier diagnosis of critical congenital heart disease (cCHD). Our aim was to test the hypothesis that POS can reduce the diagnostic gap in cCHD in daily clinical routine in the setting of tertiary, secondary and primary care centres. We conducted a prospective multicenter trial in Saxony, Germany. POS was performed in healthy term and post-term newborns at the age of 24-72 h. If an oxygen saturation (SpO(2)) ofor=95% was measured on lower extremities and confirmed after 1 h, complete clinical examination and echocardiography were performed. POS was defined as false-negative when a diagnosis of cCHD was made after POS in the participating hospitals/at our centre. From July 2006-June 2008, 42,240 newborns from 34 institutions have been included. Seventy-two children were excluded due to prenatal diagnosis (n = 54) or clinical signs of cCHD (n = 18) before POS. Seven hundred ninety-five newborns did not receive POS, mainly due to early discharge after birth (n = 727; 91%). In 41,445 newborns, POS was performed. POS was true positive in 14, false positive in 40, true negative in 41,384 and false negative in four children (three had been excluded for violation of study protocol). Sensitivity, specificity, positive and negative predictive value were 77.78%, 99.90%, 25.93% and 99.99%, respectively. With POS as an adjunct to prenatal diagnosis, physical examination and clinical observation, the percentage of newborns with late diagnosis of cCHD was 4.4%. POS can substantially reduce the postnatal diagnostic gap in cCHD, and false-positive results leading to unnecessary examinations of healthy newborns are rare. POS should be implemented in routine postnatal care.

Cardiac resynchronization therapy (CRT) is proved to prevent heart transplantation in some patients with dilated cardiomyopathy and mechanical dyssynchrony. We report of the benefit of CRT accomplished by atrial synchronized single-site left ventricular pacing in an 8-year-old boy with idiopathic dilated cardiomyopathy, normal atrioventricular conduction, borderline QRS complex duration (120 ms), and marked mechanical left ventricular dyssynchrony proved by echocardiographic speckle tracking.

Neugeborene (NG) mit kritischen angeborenen Herzfehlern (kAHF) konnen postnatal fur eine kurze Zeit klinisch unauffallig sein, so dass eine diagnostische Lucke entsteht. In einigen Studien an einzelnen Zentren wurde das Pulsoxymetriescreening (POS) als effektives, nichtinvasives, kostengunstiges Verfahren vorgeschlagen, das eine fruhere Diagnose von kAHF ermoglicht. Die Hypothese zu uberprufen, dass das POS die diagnostische Lucke bei kAHF auch bei Anwendung in der taglichen klinischen Routine in Einrichtungen der Tertiar-, Sekundar- und Primarversorgung verkleinern kann. Prospektive multizentrische Studie in Sachsen. Das POS wurde bei gesunden NG im Alter von 24 bis 72 h durchgefuhrt. NG mit pranataler Diagnose oder postnatalen klinischen Zeichen eines kAHF wurden ausgeschlossen. Eine Sauerstoffsattigung (SpO2) von ≥96% am Fus wurde als normal definiert. Bei einer SpO2 von ≤95%, die nach einer Stunde bestatigt wurde, erfolgten eine eingehende klinische Untersuchung und eine Echokardiographie. Im Zeitraum von Juli 2006 bis Juni 2007 wurden 21.830 NG aus 31 Einrichtungen in die Studie eingeschlossen. Insgesamt 33 Kinder wurden wegen pranataler Diagnose (n=22) oder klinischer Zeichen eines kAHF (n=11) vor dem POS ausgeschlossen und 506 NG erhielten kein Screening, meist aufgrund einer ambulanten Geburt (n=438; 87%). Das POS wurde bei 21.324 NG durchgefuhrt. Es war richtig-positiv bei 7, falsch-positiv bei 18 (gesund n=6, Sepsis n=2, PPHN n=10), richtig-negativ bei 21.296 und falsch-negativ bei 3 Kindern. Hieraus errechnen sich eine Sensitivitat von 70%, eine Spezifitat von 99,92%, ein positiver pradiktiver Wert von 28,0% und ein negativer pradiktiver Wert von 99,99%. Das POS kann die postnatale diagnostische Lucke bei Neugeborenen mit kAHF verkleinern. Auch Kinder mit Sepsis oder persistierender pulmonaler Hypertension (PPHN) konnen durch das POS auffallen. Falsch-positive Ergebnisse, die zu unnotigen Untersuchungen bei gesunden NG fuhren, sind ausgesprochen selten. Das POS sollte, wie dies in der Schweiz bereits geschehen ist, in die Routineversorgung von NG integriert werden.

Objective Among the complications after cardiac surgery the development of postoperative pulmonary distress is a serious problem. Typically, the patients leave the operating theatre with good blood gas values and O 2 -saturation, but develop their respiratory problems within the next hours/days. We investigated whether extracorporeal circulation may induce biochemical and histological changes in the lungs which may help to explain this development. Methods Piglets (6–10 kg) were anaesthetized using isoflurane and underwent extracorporeal circulation (ECC) with hypothermic (25–28 °C) cardioplegic arrest for 90 min followed by 3 h reperfusion. An additional group received a poly(ADP-ribose) polymerase (PARP)-Inhibitor, INO1001. Cardiopulmonary monitoring was performed during the whole procedure. Finally, lungs were explanted and investigated by histomorphometry and immunohistology for heat shock protein HSP70 (indicator for cellular damage) and TNFα in comparison to normal piglets without ECC. Results Histologically we found significant swelling of the type I alveocytes (thickness increased from 2.4 to 3.2 μm), interstitial oedema, intra-alveolar erythrocyte (4.8 versus 0.4 erythrocytes/alveole) and granulocyte accumulation and fibrinous exudates. There was a significant up-regulation of TNFα and of the cellular repair enzyme HSP70, while in control piglets only minimal levels were observed. INO1001 significantly reduced ECC-induced elevation in TNFα and in HSP70. Despite the dramatic changes after heart-lung-machine (HLM), blood gases and gas transport were almost not affected at that time. Conclusions ECC can lead to early significant histological and histochemical changes which have similarities with a beginning early stage shock lung, although – at 3 h reperfusion – gas transport is still sufficient. INO1001 can partially antagonize these changes.

Objective Closure of ostium secundum atrial septal defects is generally performed by using an interventional approach. We evaluated the outcome of patients requiring secondary surgical therapy. Methods From September 1996 until December, 2005, 418 patients received interventional and 297 patients underwent surgical closure of an ostium secundum atrial septal defect at our center. Another 15 patients (local, 5; regional, 5; and national, 5 referrals) had complications after occluder placement, and they form the study population. Results Indications for surgical repair in these 15 patients were dislocation of the occluder in 5, neurologic events after occluder placement in 5, residual defects in 4, and sepsis with questionable occluder infection in 1 patient. A total of 7 patients had neurologic events, 5 of embolic origin. The interval between interventional occluder placement and definitive surgical repair was 319 ± 416 days (median 123 days; range 0–1395 days). Patient age at operation was 34.9 ± 18.6 years. Nine patients were operated on via an anterolateral minithoracotomy, and 6 received a conventional sternotomy. One patient with sepsis underwent abdominal surgery on postoperative day 1 and subsequently died of multiorgan failure; there was no proof of occluder endocarditis. At 2.2 ± 1.9 years of follow-up, all other patients had returned to full-time work without residual neurologic impairment. Conclusions Complications may arise after interventional ostium secundum atrial septal defect closure. This must be evaluated against the extremely low risk of a standard surgical closure. The functional outcome after secondary surgical ostium secundum atrial septal defect closure with removal of an occluder system is excellent.

We report on a male newborn requiring repair of a huge left apical diverticulum leading to progressive heart failure and extensive ventricular arrhythmia. At the age of 11 days, a modified Dor procedure using an autologous endoventricular pericardial patch was performed. Postoperatively, a significant reduction of ventricular extrasystole was evident. One year postoperatively, the infant demonstrates a normal cognitive and somatic development without clinical signs of cardiac failure.

Objective Reoperations are associated with an increased surgical risk due to adhesions. We prospectively evaluated a bioresorbable membrane after surgery for congenital heart defects over a 3.5-year period. Methods The surgical membrane (CV Seprafilm, Genzyme, Cambridge, Mass) was applied in 350 of 1024 patients; 30 of them underwent reoperation and were evaluated in comparison to 10 random reoperated patients. Adhesions were evaluated using a subjective scoring system [1 (lowest tenacity) to 5 (highest tenacity)] and extent in percent at different regions of the heart. Results Patients were operated for atrioventricular septal defect (69), tetralogy of Fallot (65), functional single ventricle (75), valve surgery (48), ventricular septal defect (20), subaortic stenosis (17), hypoplastic left heart syndrome (17), and other diagnoses (39). Application of the surgical membrane was safe in all patients, without any infections. At reoperation patients received Glenn (14), total cavopulmonary connection (6), and others (10). Overall mortality was 2/350 (0.57%). There was a remarkable reduction in tenacity score (3.3 vs 4.3) and in the extent of adhesions (77.7% vs 86%). Duration of reoperation was significantly reduced. Conclusions A bioresorbable surgical membrane leads to a significant reduction in the tenacity and amount of adhesions. It is recommended for general use whenever repeat operation is anticipated in congenital as well as in adult cardiac surgery.

Objective: Transplantation of bone marrow-derived mononuclear cells (BMC) may be suitable to prevent myocardial remodeling and improve left ventricular function after myocardial infarction. However, it is unknown whether or not cardiomyocytes and BMCs can form functioning cellto-cell coupling and develop adequate electrophysiological properties. Methods: BMCs were isolated from minipig leg bones, treated with 5azacytidine (10 mM) for 24 h, cultured for 7 days and labeled with a fluoroscopic dye (DIL). BMCs were cocultured with spontaneously beating cardiomyocytes of neonatal rats. On days 4, 7 and 14 cocultured cells were analyzed. Immunhistochemistry (Connexin 43, a-actinin) was used to assess cardiomyogenic differentiation. Action potential characteristics were recorded in whole cell patch clamp mode and to investigate intercellular communication a second gap junction permeable fluoroscopic dye was brought into BMCs by microinjection (Lucifer yellow, LY). Results: From day 7 in coculture BMCs beated synchronously with neonatal rat cardiomyocytes. On day 14, 55.9% of BMCs expressed a-actinin and 98.3% were positive for gap junction protein connexin 43. BMC action potential duration (APD90) was mean 11.1 ms with dV/dtmax of 26.8 V/s and similar to atrial cardiac type. However, microinjection of LY revealed only little dye transfer into adjacent rat cardiomyocytes. Conclusions: Cocultured BMCs have the potential for early expression of muscle specific proteins in about 60% after 14 days and for cardiac gap junction proteins. Synchronous beating indicates an effective electromechanical coupling. In this heterologous setting we could prove only weak metabolic coupling. q 2004 Elsevier B.V. All rights reserved.

Background The aim of the present study was to evaluate the current outcome and reoperation rate after applying a one-stage correction strategy for interrupted aortic arch (IAA) with ventricular septal defect (VSD) and also for aortic coarctation and hypoplastic aortic arch (CoA-HyAA) with VSD beginning September 1999. Methods Twenty-four consecutive patients with IAA (n = 12) or CoA-HyAA (n = 12) with VSD underwent early one-stage correction. Patients' mean age was 12 days (range, 2 to 188); mean weight was 3.6 kg (range, 2.1 to 7.3), 6 patients were less than 2.5 kg. Three IAA were type A, 5 type B1, 3 type B2, and 1 type C. Associated anomalies included a large VSD in all, left ventricular outlet tract obstruction in 5, transposition of the great arteries, aortopulmonary window, persistent truncus arteriosus, and double-outlet right ventricle in 1 patient. Selective brain perfusion through innominate artery and selective coronary perfusion through aortic root during aortic arch reconstruction was used in all patients. Mean follow-up was 2.2 ± 0.9 years. Results There was no early, no late mortality, and no postoperative neurologic complications. Mean crossclamp duration was 72 ± 32 minutes, lowest temperature 22.8 ± 4°C and selective brain and coronary perfusion duration was 34 ± 13 minutes. Eighteen patients required delayed sternal closure at 1.7 days postoperatively. New perioperative management reduced the overall morbidity. Four patients after IAA plus VSD repair developed aortic arch restenosis and were successfully treated by balloon dilatation. One patient with d-TGA underwent right ventricular outflow tract reconstruction of right ventricular outlet tract obstruction 7 months after the initial repair. Pressure gradients across the anastomosis at most recent follow up were less than 10 mm Hg. All patients are asymptomatic and are developing normally. Conclusions One-stage complete correction is feasible in newborns with aortic arch obstruction with VSD. Complex cardiac anatomy presents no additional risk for the procedure. The early one-stage correction yields excellent surgical results and good functional outcome.

ZusammenfassungIm letzten Jahrzehnt haben sich die Operationsergebnisse bei komplizierten Eingriffen im Neugeborenenalter eindrucksvoll verbessert. Beispielhaft dargestellt werden die Diagnosegruppen Transposition der großen Arterien (TGA) und unterbrochener Aortenbogen/komplexe Aortenisthmusstenose (IAA). Angesichts der verbesserten Operationsergebnisse fällt bei der Analyse die präoperative Morbidität stärker ins Auge: Bei 70 Fällen von TGA verstarb früh postoperativ 1 Patient; im gleichen Zeitraum mussten 5 Patienten in der präoperativen Phase reanimiert werden, 1 Patient davon ohne Erfolg. In der Gruppe IAA verstarb bei 30 Fällen postoperativ kein Patient; präoperativ mussten ebenfalls 5 Patienten reanimiert werden, 1 Patient davon ohne Erfolg. Obgleich die erfolgreich reanimierten Patienten die Herzoperation überlebten, muss man auch im Hinblick auf die langfristige Prognose beunruhigt sein. Typischerweise haben diese Patienten kein Herzgeräusch und die Hypoxie manifestiert sich zunächst nicht unbedingt als sichtbare Zyanose. Diese diagnostische Lücke könnte durch ein Oxymetrie-Screening bei unauffälligen Neugeborenen zu schließen oder zu verkleinern sein, da im Einzugsbereich nur 18% der Herzfehler bereits pränatal entdeckt werden.