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.

[Modern therapy of congenital heart defects]. / Moderne Therapieverfahren bei angeborenen Herzfehlern.

Modern therapy of congenital heart defects consists of interventional and surgical procedures. The following report provides information about the most common congenital heart defects and the corresponding therapeutic options. Furthermore, the combined application of interventional and surgical procedures, so-called hybrid procedures, is described in detail as well as the latest developments in percutaneous valve replacement therapy.

Absence of donor-specific anti-HLA antibodies after ABO-incompatible heart transplantation in infancy: altered immunity or age?

Specific B-cell tolerance toward donor blood group antigens develops in infants after ABO-incompatible heart transplantation, whereas their immune response toward protein antigens such as HLA has not been investigated. We assessed de novo HLA-antibodies in 122 patients after pediatric thoracic transplantation (28 ABO-incompatible) and 36 controls. Median age at transplantation was 1.7 years (1 day to 17.8 year) and samples were collected at median 3.48 years after transplantation. Antibodies were detected against HLA-class I in 21 patients (17.2%), class II in 18 (14.8%) and against both classes in 10 (8.2%). Using single-antigen beads, donor-specific antibodies (DSAs) were identified in six patients (all class II, one additional class I). Patients with DSAs were significantly older at time of transplantation. In patients who had undergone pretransplant cardiac surgeries, class II antibodies were more frequent, although use of homografts or mechanical heart support had no influence. DSAs were absent in ABO-incompatible recipients and class II antibodies were significantly less frequent than in children with ABO-compatible transplants. This difference was present also when comparing only children transplanted below 2 years of age. Therefore, tolerance toward the donor blood group appears to be associated with an altered response to HLA beyond age-related effects.

Successful ABO-incompatible heart transplantation in a child despite blood-group sensitization after ventricular assist device support.

In the first two yr of life blood-group incompatible (ABO-incompatible) heart transplantation can be performed leading to immune tolerance to donor blood group. Antibody titers should be below 1:4. VAD use is correlated with sensitization toward blood-group antigens. A boy was diagnosed with dilated cardiomyopathy at nine months of age and listed for 0-compatible transplantation. Progressive heart failure required implantation of a left VAD. His listing was extended for ABO-incompatible transplantation despite antibody titers of 1:32 anti-A and 1:8 anti-B. After 26 days on VAD, he was transplanted with a B donor heart. No hyperacute or acute rejection occurred in 12 months post-transplant. Anti-B antibodies rose to a maximum of 1:2. No use of rituximab or plasmapheresis was required. There are no signs of graft vasculopathy. This indicates that inclusion criteria for ABO-incompatible transplantation may be extended to immediate cases. This is the first case with a healthy immune system to show signs of tolerance development after ABO-incompatible heart transplantation with increased prior antibody titers and without specific treatment.

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.

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.

[Tilt-table-testing in childhood: non-invasive, continuous hemodynamic monitoring]. / Nichtinvasives, kontinuierliches Kreislaufmonitoring bei der Kipptischuntersuchung im Kindesalter.

BACKGROUND: Approximately 15% of children experience a syncope before the age of 18 years. Tilt table testing represents the diagnostic gold standard whenever a neurocardiogenic spell is suspected. Two methods of continuous, non-invasive hemodynamic monitoring during the tilt table test are presented and their usefulness for clinical routine is discussed. PATIENTS: 4 patients with suspected neurocardiogenic syncope. METHODS: Tilt table testing according to standard protocol; non-invasive, continuous blood-pressure measurement by finger cuffs; impedance cardiography for the assessment of cardiac output. RESULTS: In 3 patients a syncope occured during the tilt table test. In pt. 4 characteristic symptoms led to diagnosis prior to syncope. Every patient represents a definite type of neurocardiogenic syncope (cardioinhibitory with asystolia, vasodepressory, mixed as well as postural tachycardia syndrome). CONCLUSIONS: Both monitoringmethods allow a differentiated analysis of the cardiovascular interactions during the tilt table test. Thus, specific regulatory patterns may be diagnosed and specific treatment strategies may be offered.

[Quantification of right ventricular function in congenital heart disease: correlation of 3D echocardiography and MRI as complementary methods]. / Quantifizierung der rechtsventrikulären Funktion bei angeborenen Herzfehlern: Korrelation von 3D-Echokardiographie und MRT als sich ergänzende Methoden.

PURPOSE: In congenital heart disease, the exact determination of the right ventricular function is of high importance for therapeutic and especially surgical planning. The aim of this study was to correlate the parameters of the right ventricular function in MRI and 3D echocardiography to determine the agreement of both modalities. MATERIALS AND METHODS: In 18 patients suffering from congenital heart disease, 3D echocardiography was performed using a Philips Sonos 7500 system. In MRI short axis slices with a 4-mm distance were acquired using an SSFP sequence on a Siemens Sonata or Symphony System. Volumetry for both modalities was performed on an external workstation (Tomtec) using the EchoView software. RESULTS: Enddiastolic and endsystolic volumes showed a highly significant correlation with coefficients of 0.996 and 0.990, respectively. In echocardiography there was a systematic slight underestimation of enddiastolic volumes and overestimation of endsystolic volumes. The Wilcoxon test did not show significant differences between the volumes and ejection fractions assessed by both modalities. CONCLUSION: There is an excellent correlation in the quantification of right ventricular volumes in MRI and 3D echocardiography, which allows a comparison of acquired volumes in clinical follow-up.

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.

Short-term testing of heart rate variability in heart-transplanted children: equal to 24-h ECG recordings?

INTRODUCTION: Heart rate variability (HRV) is reduced in adults and children after cardiac transplantation. Testing of HRV has been used to assess re-innervation of the cardiac graft; its reliability in ruling out acute graft rejection is still under investigation. This study used a short-term test on HRV in 23 heart and heart-lung transplanted children and adolescents and compared the results with 24-h ECG recordings. PATIENTS AND METHODS: Twenty-three subjects (16.3+/-4.2 yr; 10 females) underwent a 10-min HRV test at two occasions and one 24-h ECG. HRV was calculated according to the time domain method (RR interval, standard deviation of RR interval) and the frequency domain method (total power, LF and HF for assessment of sympathovagal modulation of heart rate). RESULTS: Correlation between the short-term tests and 24-h ECG was high with regard to the frequency domain analysis of HRV. Correlation was less pronounced in the time domain method. CONCLUSIONS: In heart and heart-lung-transplanted children and adolescents, due to reduced overall HRV short-term testing may give as reliable data as 24-h ECG. Therefore, especially when power spectral analysis has to be performed as a longitudinal assessment of re-innervation of the cardiac graft, short-term testing may offer an easily applicable and non-invasive diagnostic tool. Further studies are warranted to investigate whether HRV testing may contribute to rule out acute graft rejection.

Young adults born small for gestational age: is reduced baroreceptor sensitivity a risk factor for hypertension?

UNLABELLED: BACKGROUND. Adults born small for gestational age (SGA) are at increased risk for the metabolic syndrome and cardiovascular disease. HYPOTHESIS: Impaired short-term blood pressure regulation may contribute to the development of hypertension in patients born SGA. METHODS: In all, 43 patients born SGA (18 female, age 19.4 +/- 0.3 years) were evaluated by beat-to-beat blood pressure and heart rate registration during rest and mental and orthostatic stress. The study group was divided into Group 1 with normal resting blood pressure (n=32) and Group 2 with slightly elevated blood pressure (n=11). Baroreceptor sensitivity (BRS) was calculated. Fasting insulin as well as lipid levels were correlated with hemodynamic parameters. RESULTS: Eleven of the 43 study patients (25%) had a slightly elevated resting systolic blood pressure (SBP) rising during mental and orthostatic stress. Body mass index (BMI) and fasting insulin levels correlated strongly with SBP in Group 2. Baroreceptor sensitivity was lower in Group 2 at rest (p < 0.05). CONCLUSIONS: Three components of metabolic syndrome (elevated BP, high BMI, elevated insulin levels) correlate strongly in young adolescents born SGA; BRS is reduced in prehypertensive patients. Close follow-up is warranted during adult life as they are predisposed for developing a metabolic syndrome with elevated cardiovascular risk.

Impedance cardiography and beat-to-beat blood pressure monitoring in diagnosis of syncope in long-QT syndrome.

Syncope represents a diagnostic challenge in patients affected by long-QT syndrome (LQTS). It is crucial for the therapeutic decision to distinguish between potentially life-threatening ventricular tachycardias (Torsadede-pointes) and-especially during adolescence-neurocardiogenic syncopes. This case report presents a patient with LQTS2 (mutation in the HERG gene) on medication with beta-blocker, in whom a head-up-tilt table test was performed after syncope of unknown origin. The test was chosen in order to reproduce the circumstances under which the syncope had happened. The monitoring device consisted of impedance cardiography as well as non-invasive beat-to-beat blood-pressure measurement. By these means it was possible to register a reduced peripheral vascular resistance after tilting the patient, a reduced cardiac output and bradycardia leading to syncope after four minutes of upright posture. This was suggestive for neurocardiogenic syncope as a cause for the spell experienced. Further non-invasive diagnostic methods were normal. As the patient's family history was negative for syncopes, Torsade-de-pointes seemed unlikely.In this special case the non-invasive monitoring system of cardiac output, peripheral vascular resistance and beat-to-beat blood pressure measurements was useful as a supplemental tool during evaluation of syncope and helpful in decision-making against implantation of an ICD and for a more intense treatment with betablockers. Such monitoring devices offer new insights into the orthostatic regulation in young patients.

Heart failure in pediatric patients.

Paradigms in understanding heart failure have changed as the knowledge of pathophysiology and its molecular basis has deepened. In the chronic compensated state of heart failure recent research has focussed on the body's regulatory mechanisms. Today heart failure is understood as a complex interplay of hemodynamic and neurohormonal factors. In pediatrics a large variety of heterogeneous conditions cause heart failure. Some require special therapeutic approaches such as the infusion of prostaglandin for ductal patency, the careful maintenance of balance between systemic and pulmonary circulations or operative treatment. In newborns with critical congenital lesions and in patients in the postoperative period management of acute heart failure becomes important. Chronic heart failure as it is understood today is present in patients with cardiomyopathies and in an increasing number of pediatric patients after palliative surgery. In heart failure due to left-to-right shunts a similar activation of compensatory neurohormonal mechanisms as in adults with chronic heart failure was found. In small clinical trials treatment of these activated compensatory mechanisms with angiotensin-converting enzyme inhibitors and beta-blockers showed beneficial effects in pediatric patients. However large clinical multicenter trials as performed in the adult population should be conducted.

Results of pediatric cardiac transplantation -- long-term results of a 15-year experience.

INTRODUCTION: Heart transplantation (HTx) has increasingly become a therapeutic option for end-stage heart failure of any origin in children. Short- and mid-term results are promising. However, long-term outcome has been a matter of concern because of acute or chronic rejection and side effects of immunosuppression. We performed a retrospective study of up to 15-years of follow-up on this patient entity. METHODS: Between 1988 and 2004, 58 HTx were performed in 55 children (cardiomyopathy (DCM) 32, congenital heart disease (CHD) 23, Re-HTx 3). Mean age was 9.1 +/- 7.2 years (4 days - 17.9 years). Twenty-nine patients had a total of 51 previous operations. RESULTS: Operative mortality was 4/58 (6.8 %) due to primary graft failure. Late mortality was 7/54 (12.1 %) due to acute rejection (2), pneumonia (2), intracranial hemorrhage (1), suicide (1) and lymphoma (1). Mean follow-up was 5.2 +/- 4.2 years. One-, 5-, and 10-year survival was 86 %, 80 % and 80 %, respectively, and improved significantly after 1995 (92 % and 92 %; p = 0.04). Survival was comparable for DCM and CHD patients (1-year: 88 % vs. 82 %; p = 0.19; 5-years: 84 % vs. 77 %; p = 0.12). Three patients with therapy resistant rejection and assisted circulation required retransplantation and are alive. Freedom from acute rejection was 46 % with primary cyclosporine immunosuppression and 63 % with tacrolimus. Ninety-eight percent of the survivors are at home and in excellent cardiac condition. CONCLUSION: Pediatric heart transplantation is a curative treatment for DCM and CHD with excellent clinical mid-term results. However, further follow-up is necessary to evaluate long-term side effects of immunosuppressants. Donor shortage remains a problem.

["Real time"-3D-echocardiography: a valuable new tool in preoperative assessment of complex cardiac defects]. / "Real Time"-3D-Echokardiographie: Erfahrungen im Kindesalter. Fallbeispiel für die Einsatzmöglichkeit der dreidimensionalen Echtzeit-Echokardiographie in der präoperativen Abklärung angeborener Herzfehler.

Evaluating complex cardiac defects in small children preoperatively requires multiple diagnostic procedures including echocardiography, but also the invasive methods such as cardiac catheterisation, computer-tomography and magnetic resonance imaging. We tried to assess the complex anatomy of the atrioventricular valves in atrioventricular septal defect using bedside real-time three-dimensional echocardiography and comparing these results to the anatomic findings at the time of operation.

[15-year-old patient with decompensated heart failure and tachycardia with negative P-waves in inferior ECG recordings. An indication for heart transplantation?]. / 15-jährige Patientin mit dekompensierter Herzinsuffizienz und Tachykardie mit negativen P-Wellen in inferioren EKG-Ableitungen. Eine Indikation zur Herztransplantation?

A 15-year-old girl was admitted with signs of severe cardiac failure. There were no symptoms of cardiac insufficiency 4 weeks before hospital admission. She presented with permanent supraventricular tachycardia with negative P-waves in leads II, III and aVF, the heart rate was 150 beats per minute. The electrophysiological examination showed a permanent junctional reentry tachycardia. A postero-septal accessory pathway could be eliminated successfully by radiofrequency catheter ablation. Immediately after the procedure cardiac function deteriorated with slight decrease of the strongly reduced cardiac output. Intensive care and application of dobutamine led to clinical stability. During a follow-up of two years the young patient showed permanent sinus rhythm and an age related physical strain. This case report documents the rapid and severe manifestation of cardiac failure owing to permanent junctional reentry tachycardia in a 15-year-old girl. She was referred for consideration of heart transplantation. Invasive electrophysiological treatment led to permanent sinus rhythm with improvement of left ventricular function.

Real-time three-dimensional ultrasound - a valuable new tool in preoperative assessment of complex congenital cardiac disease.

Evaluating complex cardiac defects in small children preoperatively requires multiple diagnostic procedures including echocardiography, and also invasive methods such as cardiac catheterisation, computer-tomography and magnetic resonance imaging. We assessed the complex anatomy of the atrioventricular valves in atrioventricular septal defect using bedside real-time three-dimensional echocardiography and comparing these results to the anatomic findings at the time of operative intervention.

Borderline hypoplastic left heart malformations: Norwood palliation or two-ventricle repair?

BACKGROUND: Patients with hypoplastic left heart syndrome (HLHS) and associated malformations undergo Norwood palliation or potentially a two-ventricle repair. METHODS: Since 8/99, 8 patients with typical HLHS and two with DILV underwent Norwood/Fontan palliation (group I). Three other patients (group II) had two-ventricle repair. Anatomy was: aortic atresia, coarctation, unrestrictive VSD (patient 1), hypoplastic mitral and aortic valve, arch and LV, coarctation (patients 2 and 3). Surgical procedures were Norwood arch reconstruction with either Rastelli operation (patient 1) or ASD-closure (patients 2 and 3). RESULTS: Operative mortality in group I was 1/8 (day 22; RV-failure). Two patients died before Glenn (sepsis, RV-failure). Six patients underwent Glenn procedure successfully. No patient died in group II. Echocardiography after 13 +/- 7.4 months showed mild homograft dysfunction (patient 1) and an LVOT-gradient of 20 mmHg (patient 3). Clinical condition of all survivors in both groups is good. CONCLUSION: Some anatomical subsets of HLHS with borderline mitral valves and small left ventricles may undergo two-ventricle repair despite severe LVOTO. Mortality and morbidity seem to be lower, but selection criteria are so far not defined.