Prophylactic effect of angiotensin receptor blockers in children with genetic aortopathies: the early bird catches the worm.

AIMS: In genetic aortopathies (GA) particular attention is paid to aortic root dilatation which has an impact on morbidity and mortality. This study focuses on the effects of therapy with angiotensin-II-receptor-blockers (ARB) or beta-blockers (BB) on aortic root growth and the question which therapy should be initiated at which dosage and at what age. METHODS: Since 1998 we diagnosed 208 patients with GA (170 FBN-1). 81 patients between 5 months and 18 years receiving either ARB or BB therapy were included. We retrospectively analyzed the progression of the dilatation of Sinus Valsalva aortae (SV) using calculated z-scores before and after therapy initiation and compared BB and ARB treatment. RESULTS: Both ARB and BB (p < 0.05) therapy showed significant improvement in aortic root growth, while the effect is significantly more pronounced in ARB (p < 0.01) independent of age and genetic cause. A detailed comparison of the two drug groups showed a more sustained effect in limiting the progression of the dilatation of the aortic root in patients treated with ARB. Progression of dilatation of the SV was significantly lower in children treated with ARBs compared to BB (delta z-score, p < 0.05). In addition, ARBs were better tolerated and had a significantly lower discontinuation rate (3%) compared to BB (50%) (p < 0.01). Independently of age at initiation all children and adolescents were able to reach the target dose under ARB. CONCLUSION: We demonstrated a significant change in both treatment options, with the effect of ARB being more pronounced while being better tolerated throughout the treatment period.

Alveolar capillary dysplasia with left heart obstruction - rare but lethal.

Alveolar capillary dysplasia (ACD) is a rare neonatal lung disease characterized anatomically by a defective and hypoplastic development of pulmonary alveoli leading to persistent pulmonary hypertension (PPHN) and finally lethal respiratory failure. It is often associated with congenital left heart obstruction. Given the fatal prognosis an early diagnosis is important. However, due to the fast onset of PPHN in neonates and lack of pathognomonic signs for its cause, safe and fast detection of ACD is challenging. Therefore, following the exclusion of cardiac and common pulmonary causes, lung biopsy becomes essential for diagnosis.We hereby report a case of ACD with atrial septal defect type one and hypoplastic aortic arch with an ante-mortem diagnosis and discuss the current state of medicine in relation to ACD.

[Clinical classification and initial diagnosis of pulmonary hypertension: recommendations of the Cologne Consensus Conference 2016]. / Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

[Pulmonary hypertension in grown-ups with congenital heart disease: Recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Erwachsenen mit angeborenen Herzfehlern: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for different forms of PH, and specifically address PH associated with congenital heart disease (CHD). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH in grown-ups with congenital heart disease (GUCH). This article summarizes the results and recommendations of this working group.

ABO-compatible retransplantation after ABO-incompatible infant heart transplantation: absence of donor specific isohemagglutinins.

Implementation of ABO-incompatible (ABOi) pediatric heart transplantation has contributed to significant reduction in the mortality of infants on the waiting list, without increasing the risk of rejection. This has been attributed to the immature and therefore not fully competent immune system in this population group, which results in lower production of isohemagglutinins compared to older children and adults. Serial evaluations of isohemagglutinin titers in infants revealed cases with absence of donor specific anti-blood group antibodies. However, it is currently unknown whether continuous exposure to donor antigens is necessary to prevent formation of donor specific isohemagglutinins (DSI) in recipients. We are reporting a case of an infant who underwent ABOi heart transplantation, with no evidence of DSI even 4 years after ABO-compatible retransplantation. Hence, temporary exposure to donor antigens in infants may contribute to permanent absence of donor specific anti-blood group antibodies, suggesting the possibility of induced permanent B cell tolerance.

[Minimally invasive pulmonary valve replacement in pediatric patients: importance of imaging]. / Minimal-invasiver Pulmonalklappenersatz bei pädiatrischen Patienten: Stellenwert der Bildgebung.

CLINICAL/METHODICAL ISSUE: Right ventricular outflow tract (RVOT) dysfunction with pulmonary regurgitation or obstruction is a common postsurgical consequence in congenital heart disease. STANDARD RADIOLOGICAL METHODS: Magnetic resonance imaging (MRI) is widely accepted as standard method of imaging in congenital heart disease. It provides anatomical and functional information without radiation exposure and is therefore well suited for serial examinations. METHODICAL INNOVATIONS: Percutaneous pulmonary valve implantation (PPVI) has been shown to be a safe and effective treatment option for patients with pulmonary valve insufficiency or stenosis. Correct patient selection for PPVI is crucial. It is important to be familiar with the indications and anatomical requirements for stent placement and to tailor imaging protocols. PERFORMANCE: Imaging the RVOT, assessment of right ventricular volumes and function and calculation of pulmonary flow and regurgitation are core elements of the MRI examination prior to PPVI. Low interobserver and intraobserver variation allows even small changes to be detected. ACHIEVEMENTS: Imaging provides relevant information for correct patient selection for PPVI and is part of postinterventional follow-up. Imaging is an important tool for documentation of success and for detection of complications. PRACTICAL RECOMMENDATIONS: Several imaging modalities are used for evaluation of RVOTs; however, MRI can provide answers to most questions without radiation exposure.

[MRI for therapy planning in patients with atrial septum defects]. / MRT zur Therapieplanung bei Patienten mit Vorhofseptumdefekt.

PURPOSE: The aim of this study was to determine the value of a combined magnetic resonance imaging (MRI) protocol including steady-state free precession (SSFP) imaging, phase-contrast measurements and contrast-enhanced MR angiography (CE-MRA) for presurgical or preinterventional diagnostic imaging in patients with suspected atrial septum defects. MATERIAL AND METHODS: Out of 65 MRI studies of patients with suspected atrial septum defects, 56 patients were included in the study. The atrial septum defects were identified on cine images. Velocity encoded flow measurements were used to determine shunt volumes, which were compared with invasive oxymetry in 24 patients. Contrast-enhanced MRI was used to assess the thoracic vessels in order to detect vascular anomalies. The findings were compared with the intraoperative results. RESULTS: A total of 24 patients with high shunt volumes were treated either surgically (16 patients) or interventionally (8 patients) and 32 patients with low shunt volumes did not require surgical or interventional treatment. The vascular anomaly, which in all cases was anomalous pulmonary venous return, was confirmed by the intraoperative findings. The type and location of atrial septal defects which required treatment, were confirmed intraoperatively or during the intervention. The results of shunt quantification by MRI showed a good correlation with the results of invasive oximetry (r=0.91, p <0.0001). CONCLUSION: A combined MRI protocol including cine SSFP images, velocity-encoded flow measurements and CE-MRA is an accurate method for preoperative and preinterventional evaluation of atrial septum defects.

Interventional closure of two fistulas after aortic valve surgery.

INTRODUCTION: Paravalvular fistulas may complicate the clinical course after heart valve surgery. Medical treatment may be ineffective, repeated surgical revisions may be associated with increased morbidity and mortality. CASE REPORT: After valve sparing surgery in bicuspid aortic valve, a significant aorto-left atrial fistula was diagnosed in a 72-year-old patient causing heart failure and catecholamine-dependency. Due to the critical hemodynamic state, percutaneous closure was performed with an AGA Amplatzer duct occluder. Secondary to this closure, a second fistula between the aortic root and the right atrium appeared which was closed during the same procedure implanting a second duct occluder beneath the first device. CONCLUSION: Percutaneous closure of paravalvular fistulas is feasible and a safe method for the treatment of significant shunts after valve surgery. Even in multiple fistulas, the implantation of small devices allows for a focussed interventional closure of such leaks. This procedure should be considered for such defects as it represents a safe method for the causative treatment in paravalvular lesions after valve surgery especially in patients with critical hemodynamic conditions.

"Rapid two-stage" Norwood operation in a child with multiorgan failure.

The Norwood I operation continues to be a procedure with significant operative mortality. One well-accepted risk factor for death after the first step of the Norwood operation is critical preoperative status. We describe herein a new concept for the treatment of patients with hypoplastic left heart syndrome (HLHS) in very poor preoperative condition. This is a case report of a child who was born in a rural hospital. On the second day of life he was referred to our center in multiorgan failure. There were signs of liver dysfunction and the child was anuric. Therapy was started immediately with prostaglandin and vasodilators as well as diuretics, milrinone, and dobutamine. However, systemic perfusion continued to be insufficient. Finally, the child was placed on a ventilator. On the fourth day of life, bilateral pulmonary artery (PA) banding was performed and circulation stabilized immediately. Two hours after the operation urine output started. Liver function stabilized over the next couple of days. Two days after PA banding the child was weaned from the ventilator. On the 12th day of life a Norwood operation with PA debanding and a right ventricle-PA conduit was performed, and 2 days postoperatively the child was weaned from the ventilator. Twenty days after the operation he was discharged home. When the boy was 4 months old a bidirectional cavopulmonary anastomosis was performed. In selected cases of patients with HLHS with very poor hemodynamic conditions, a rapid two-stage approach with bilateral banding followed by a Norwood operation after cardiac stabilization can be recommended.

Creation of ventricular septal defects on the beating heart in a new pig model.

BACKGROUND/AIMS: So far, surgical and interventional therapies for muscular ventricular septal defects (mVSDs) beyond the moderator band have had their limitations. Thus, alternative therapeutic strategies should be developed. We present a new animal model for the evaluation of such strategies. METHODS: In a pig model (n = 9), anterolateral thoracotomy was performed for exposure of the left ventricle. mVSDs were created under two- and three-dimensional echocardiography with a 7.5-mm sharp punch instrument, which was forwarded via a left ventricular puncture without extracorporeal circulation. RESULTS: Creation of mVSDs was successful in all animals (n = 9) confirmed by echocardiography, hemodynamic measurements and autopsy. The defects were located in the midmuscular (n = 4), apical (n = 1), inlet (n = 2) and anterior part (n = 2) of the muscular septum. All animals were hemodynamically stable for further procedures. The diameter and shunt volume of the mVSDs were 4.8-7.3 mm (mean: 5.9 mm) and 12.9-41.3% (mean: 22.1%), respectively. Autopsy confirmed in all animals the creation of a substantial defect. CONCLUSION: The described new technique for creation of an mVSD on the beating heart in a pig model is suitable for the evaluation of new therapeutic strategies for mVSD closure.

Impaired short-term blood pressure regulation and autonomic dysbalance in children with type 1 diabetes mellitus.

AIMS: Because reduction in baroreceptor sensitivity (BRS) has been associated with hypertension in the normal population and with increased cardiovascular morbidity and mortality in patients with diabetes mellitus, we measured BRS in a patient cohort of children with type 1 diabetes mellitus. METHODS: Two hundred and eight children (150 patients with type 1 diabetes mellitus, mean age 13.9 +/- 2.8 years, 70 boys, mean HbA(1c) 7.8 +/- 1.4%; and 58 healthy controls, mean age 14.1 +/- 3.1 years, 32 boys) were studied. BRS and heart rate variability (HRV) were analysed from a short-time ECG and BP recording using the sequence method (BRS) and the frequency domain method (HRV). RESULTS: There were 111 of 150 patients (74%) and 5 of 58 controls (8.6%) that showed impaired BRS. Mean BRS differed significantly between patients and controls (18.4 +/- 7.2 vs 25.8 +/- 8.2 ms/mm, p < 0.001). BRS correlated inversely with systolic BP (r = -0.23, p = 0.009) and was related to diabetes duration (r = -0.194, p = 0.027). Analysis of HRV showed greater sympathetic and less parasympathetic influence in patients than in controls (low frequency/high frequency ratio 1.3 +/- 0.8 vs 0.9 +/- 0.6, p < 0.05); the low frequency/high frequency ratio was inversely correlated with BRS (r = -0.28, p = 0.001). CONCLUSIONS/INTERPRETATION: Diabetic children show reduced BRS. In our patient group, the single risk factor for this finding was found to be the disease duration. The degree of BRS impairment was related to the degree of autonomic dysbalance.

Surgical management in paediatric patients with left abnormal subclavian artery and right aortic arch.

Left abnormal subclavian artery and right aortic arch is described as a rare cause of dyspnoea and dysphagia in paediatric patients. The optimal surgical management of such cases is not clearly established. We propose a single-stage repair by transection of the patent ductus arteriosus or ligamentum arteriosum and an additional transection of the left abnormal subclavian artery with reimplantation into the common carotid artery.

Successful single lung fontan operation in 2 children: case reports.

We report on 2 children, aged 3 and 4 years, with single ventricle physiology who underwent Fontan operation in the presence of a single right lung successfully with good midterm outcome. Therefore, the absence of one lung is not a contraindication for a Fontan palliation in selected patients with optimal hemodynamics.

Challenging venous reconstruction and heart transplantation in a patient with viscero-atrial situs inversus and complex congenital heart disease with Fontan circulation.

Heart transplantation represents a valuable therapeutic option for patients with congenital heart disease and end-stage heart failure. We report the case of a 15-year-old patient with situs inversus and additional complex congenital malformations of the heart who underwent several previous palliative operations. Orthotopic cardiac transplantation with several technical modifications was performed successfully. At 18 months post-operatively the patient is free from rejection and doing well in New York Heart Association (NYHA) Class I status.

Recurrent pericarditis in children: elevated cardiac autoantibodies.

UNLABELLED: Recurrent pericarditis is a rare disease in childhood. Nevertheless, it may represent a challenge to the clinician due to its resistance to anti-inflammatory treatment. The initial etiology often remains unclear; specific laboratory parameters predicting the frequency or severity of the recurrences are lacking. We report on four patients with recurrent pericarditis in whom antimyolemmal antibodies (AMLAs) were detected. A prolonged persistence of IgM-type AMLAs was found in three patients: two of them presented with acute inflammation as the initial event and one with 48 recurrences during 5.5 years. The fourth patient showed a fast conversion from IgM to IgG-type AMLAs after a less acute initial presentation and showed 4 mild recurrences during the 48-month follow-up. CONCLUSION: We were able to detect AMLAs in four children with recurrent pericarditis. This finding may be attributed to an auto-immunological disease following a first, acute event. We propose the detection of AMLAs in all children with unexplained recurrent pericarditis. Pediatric patients with a persistence of IgM-type AMLAs may face frequent recurrences and should be monitored therefore more closely. In addition, medical treatment may be changed in these patients with a slower tapering of the dosage of steroidal and non-steroidal antiinflammatory drugs.

Calculating sympathovagal balance from heart rate variability: are there alternatives in adolescents?

OBJECTIVE: Assessing sympathovagal balance by calculating LF/HF-ratio from power spectral analysis (PSA) of heart rate variability (HRV) may be difficult in adolescents as chaotic breathing leads to methodical bias and metronomic breathing is not easy to perform. Diastolic blood pressure variability (dBPV) is less influenced and may therefore offer more stable values for calculations. The present study was performed on 72 paediatric subjects to investigate possible alternative LF/HF-calculations from PSA of HRV and dBPV. METHODS AND RESULTS: Seventy-two paediatric individuals in three groups: 12 controls, 17 heart- and heart-lung-transplanted children (TX) and 43 adolescents born small for gestational age (SGA). Short-term beat-to-beat HRV and BP-recordings were made supine and during active standing. Ratios calculated: LF/HF from HRV, LF/HF from dBPV, LF-dBPV/HF-HRV and LF-HRV/HF-dBPV. LF/HF from dBPV as well as LF-HRV/HF-dBPV did not correlate with LF/HF-HRV. Correlation of LF/HF from HRV and LF-dBPV/HF-HRV was high especially in TX and in patients with resting heart rate of above 90 beats per minute. CONCLUSIONS: In adolescents, the ratio of LF-dBPV/HF-HRV may be an alternative method for calculating sympathicovagal balance being less influenced by breathing patterns. In younger patients with elevated resting heart rate, but also in patients with very low HRV such as TX-patients this method could be a supplemental diagnostic tool whenever autonomic nervous control on the cardiocirculatory system has to be assessed.

First experience with the 2005 modified Gore Helex ASD occluder system.

We report about our initial experience for the in 2005 modified Helex (Gore) device for closure of atrial septal defects (ASD) and persistent foramen ovale (PFO). Major changes were made at the delivery system for simplifying the Helex implantation procedure. We treated 11 patients, 8 children and 3 adults, with ages between 3 and 62 years. In 10 patients the diagnosis was a relevant ASD with volume overload of the right heart (Left to right shunts between 30 and 50%). One adult (age 58 years) have had a small left to right shunt with a PFO-like defect and the history of 2 neurologic embolic events. In 3 patients we found 2 defects. In all patients a Helex occluder was implanted successfully. The mean fluoroscopy time was 8,4 minutes. The immediate occlusion rate after 24 hours was 91%. In all cases there was a very good adaptation of the device to the anatomical structures. In this small series, the Helex occluder appears to offer a reliable system of occlusion for small and moderate ASDs and for PFO with minimal risk of major complications.