Creation of a restrictive atrial left-to-right shunt: a novel treatment for heart failure.

Elevated left atrial (LA) filling pressures are associated with poor prognosis in patients with heart failure (HF). Recent evidences have shown that, in this setting, the presence of restrictive small atrial defect may protect from an extreme increase in LA pressure and prevent consecutive pulmonary congestion and acute decompensation, without the expense of an unfavourable significant left-to-right shunt. Therefore, decompression of LA by creating a unidirectional but restrictive left-to-right interatrial shunt has been emerging as a new therapeutic strategy in patients suffering from both HF with preserved and reduced ejection fraction. Two dedicated devices (V-Wave and interatrial septal device system-IASD) are currently available to create a restrictive interatrial communication. Several clinical studies have demonstrated the safety of this approach, with encouraging results regarding the improvements in haemodynamic parameters, functional status and quality of life in treated patients. We aim to summarize the present knowledge concerning this novel therapeutic approach for HF, describe the currently available devices and depict their potential future clinical indications.

Reduction in cortisol inactivation is part of the adrenal stress response to cardiac and noncardiac pediatric surgery: a prospective study using gas chromatography-mass spectrometry analysis.

We examined the hypothesis that major cardiac surgery triggers a more intense adrenal stress response than less intensive noncardiac surgery, which then alters cortisol inactivation. Urinary excretion rates of glucocorticoid metabolites were determined before and after surgery using gas chromatography-mass spectrometry in 29 children undergoing scheduled major cardiac surgery and 17 control children undergoing conventional noncardiac surgery in a prospective observational study. Excretion rates of glucocorticoid metabolites were summed and corrected for creatinine excretion to calculate cortisol production rates (mg/mmol creatinine/m(2) body surface area). Precursor/product ratios from individual metabolites were calculated to characterize cortisol inactivation (11ß-hydroxysteroid dehydrogenase). Postoperatively, median cortisol production rates increased in both groups ( MCS: from 2.7 to 9.3; controls: from 2.7 to 5.8; p<0.001) with no significant difference between groups (p=0.12). Ratios of cortisol to cortisone metabolites, indicating the overall activity of 11ß-hydroxysteroid dehydrogenase, increased postoperatively in both groups (p<0.001). In conclusion, surgery resulted in a distinct postoperative increase in cortisol production. In contrast to our hypothesis, children undergoing major cardiac surgery did not show an increased adrenal stress response compared to children undergoing conventional surgery. Furthermore, the reduction in cortisol inactivation appears to be an essential part of the stress response to pediatric surgery in general.

Prenatal assessment of ventriculocoronary connections and ventricular endocardial fibroelastosis in hypoplastic left heart.

OBJECTIVE: The outlook for newborns with hypoplastic left heart (HLH) has substantially improved over the last decade. However, differences in outcome among various anatomical subgroups have been described. We aimed to describe the incidence of ventriculocoronary communications and endocardial fibroelastosis in HLH and the possible implication on hospital survival (30 d). METHODS: We retrospectively reviewed our medical records, still frames and video loops of 72 fetuses with HLH and critical aortic valve stenosis and evolving HLH from 2008 - 2013. The presence of VCAC and EFE were systematically assessed. Outcome parameters were incidence of VCAC and EFE among different anatomical subgroups of HLH and hospital survival (30 d). RESULTS: 72 fetuses were included in this series. The incidence of VCAC was 11.1 % (8 cases) and EFE occurred in 33.3 % (24 cases). 5 fetuses with VCAC occurred in the subgroup of mitral valve stenosis/aortic valve atresia (MS/AA, 62.5 %) and 2 fetuses with VCAC occurred in the group of mitral atresia/aortic valve atresia (MA/AA, 25 %). Further classification was not possible in one case with VCAC (12.5 %). EFE predominantly occurred in the subgroup of MS/AA, MA/AA and in those cases with aortic valve stenosis and evolving HLH. The overall hospital survival on an intention-to-treat basis was 91.2 % (52/57 newborns). Hospital survival was 91 % for the subgroup of cases with MS/AA and for all other anatomical subgroups. CONCLUSION: The presence of VCAC in HLH can be diagnosed by fetal echocardiography predominantly occurring in cases with obstructed outflow and to some extent patent mitral valve. EFE is a frequent coexisting finding. Hospital survival was comparable among different anatomical subgroups and in cases with VCAC. The presence of VCAC in HLH did not limit the results of surgical palliation within the observation period of 30 days.

Fetal cardiac catheterization using a percutaneous transhepatic access technique: preliminary experience in a lamb model.

OBJECTIVES: Human fetal cardiac intervention has hitherto typically involved a percutaneous transventricular approach. In fetal lambs, a transhepatic approach to access the fetal intra-abdominal veins after exteriorization of the uterus by laparotomy has been described. We aimed to develop a percutaneous transhepatic technique for catheterization of the fetal heart at mid-gestation that avoids maternal laparotomy. METHODS: In 10 fetal lambs (90-97 days' gestation), access to the fetal venous system was attempted by percutaneous puncture with a 5-F sheath into the umbilical vein (n = 1) or a 16-gauge IV-catheter into the hepatic vein (n = 9). This was followed by cardiac catheterization using a 1.8-2.6-F tapered coronary catheter. Euthanasia and postmortem examination were performed immediately postprocedure in two cases, or after normal term delivery in the remaining cases that survived the procedure. RESULTS: In one case fetal position precluded procedural attempts, and in another, the fetus, accessed by a 5-F sheath, died from umbilical hemorrhage. In eight cases, access to the fetal hepatic vein was achieved. In seven of these cases, the access catheter was advanced into the inferior vena cava, followed by catheterization of the right atrium (all cases) and four cardiac chambers (three cases). One fetus died during cardiac catheterization owing to right ventricle perforation, and the other seven fetuses were alive at the end of the procedure (87.5% survival). Immediate postmortem after euthanasia in two of the fetuses that survived the procedure detected intraperitoneal bleeding (4 mL and 20 mL), while postnatal postmortem examination following uneventful delivery at term in the remaining five fetuses revealed no vascular or cardiac trauma. CONCLUSIONS: Ultrasound-guided percutaneous transhepatic cardiac catheterization is feasible in mid-gestational fetal sheep. This technique has the potential for translation into human fetal cardiac and circulatory interventions.

The development and validation of a health-related quality of life questionnaire for pre-school children with a chronic heart disease.

PURPOSE: Heart diseases are often associated with residual injuries, persisting functional restrictions, and long-term sequelae for psychosocial development. Currently, there are no disease-specific instruments to assess the health-related quality of life (HrQoL) of pre-school children. The aims of this study were to develop a parent proxy instrument to measure the HrQoL of children aged 3-7 years with a heart disease and to confirm its validity and reliability. METHODS: Items from the Preschool Pediatric Cardiac Quality of Life Inventory (P-PCQLI) were generated through focus groups of caregivers. In a pilot study, comprehensibility and feasibility were tested. Five subdimensions were defined theoretically. Psychometric properties were analysed within a multicentre study with 167 parental caregivers. RESULTS: The final 52-item instrument contains a total score covering five moderately inter-correlated dimensions. The total score of the questionnaire showed a very high internal consistency (Cronbachs' α = 0.95). Test-retest correlation was at r tt = 0.96. External validity was indicated by higher correlations (r = 0.24-0.68) with a generic paediatric quality of life questionnaire (KINDL) compared to the Strengths and Difficulties Questionnaire (r = 0.17 to 0.59). Low P-PCQLI total scores were significantly associated with inpatient as opposed to outpatient treatment (t = 6.04, p < .001), with at least moderate disease severity ((t = 5.05, p < .001) NYHA classification) and with poorer prognosis (t = 5.53, p < .001) as estimated by the physician. CONCLUSIONS: The P-PCQLI is reliable and valid for pre-school children with a heart disease. It could be used as a screening instrument in routine care, and for evaluation of HrQoL outcomes in clinical trials and intervention research.

The dilemma of subaortic stenosis--a single center experience of 15 years with a review of the literature.

OBJECTIVE: The term "subaortic stenosis" includes a variety of obstructions of the left ventricular outflow tract (LVOT), ranging from a short (discrete) subvalvular membrane to long, tunnel-like narrowing. An association with other congenital lesions is frequent. We reviewed the reported literature and describe our results, analyzing the nomenclature of and risk factors for restenosis after surgical treatment. METHODS: From 1994 to 2009, 81 children (53 males, 28 females; median age: 57 months, range [ R]: 5-204) underwent surgical relief of a subaortic stenosis. Patients were divided, according to pathology, into short segment (group A, n = 42) and complex obstructions (group B, n = 39), with the latter including long segment stenosis and/or associated anomalies such as aortic coarctation, interrupted aortic arch or Shone's complex. RESULTS: Surgery resulted in a significant reduction of the gradient between the left ventricle and the aorta in both groups (Δ P group A: 51 ± 28 mmHg, group B: 46 ± 25 mmHg). There was no operative mortality. One patient died in the early postoperative period due to pericardial tamponade. Median follow-up was 90 months (R = 0.5-187). Twenty-five (31%) patients required reoperation because of recurrent stenosis after a median of 43 months (R = 0.5-128). Seven (16%) patients belonging to group A developed restenosis, and 18 (46%) in group B. Freedom from reoperation for all patients was 60% after 10 years. 10 (40%) of the patients of group B were ultimately treated with a Ross-Konno reconstruction of the LVOT. CONCLUSION: Despite adequate surgical resection, recurrence of subaortic stenosis within several years after initial surgical treatment is frequent, especially in patients with complex lesions. In cases requiring reoperation, the surgical therapy is often extensive, and even includes Ross-Konno reconstruction of the LVOT.

The fate of the pulmonary autograft in the aortic position: experience and results of 98 patients in twelve years.

OBJECTIVE: The ideal prosthesis for aortic valve replacement in infants and adolescents is still controversially discussed. Implantation of mechanical prostheses or homografts is associated with serious risks such as reoperations, thromboembolic events and infections. This has led many surgeons to prefer the Ross operation. METHODS: Between 1996 and 2008 we performed Ross operations in 98 children and infants with a mean age of 11 years (range 1 mo-25 y), including concomitant procedures (n = 33). The operation was performed as a full-root replacement in 97 and as a subcoronary implantation in one patient. The patients were followed for up to twelve years (follow-up complete) to determine clinical and echocardiographic parameters. Mean duration of follow-up was 60 +/- 37 (range 3-150 months). RESULTS: Overall survival was 98 % (n = 96). In 70 patients (71.4 %) no autograft insufficiency (AI) could be observed. AI grade I was present in 22 patients (22.4 %), AI grade II in 3 patients (3 %), and AI grade III in one patient. The autograft in the latter patient was replaced by a mechanical prosthesis. Aortic root dilatation was observed in 10 patients (10.2 %). Z-score (median) in these patients was 4.1 (normal z-score < or = 2.4). One patient with aortic root dilatation was reoperated. A pacemaker was implanted in two patients. No patient is on constant anticoagulants. CONCLUSION: The anatomy and physiology of the LVOT is best restored by the implantation of a pulmonary autograft. This additionally provides a growth potential for infants at low risk for reoperations. Autograft dilatation is a risk that requires constant evaluation.

Transcatheter Implantable Devices to Monitoring of Elevated Left Atrial Pressures in Patients with Chronic Heart Failure.

Elevated left atrial (LA) pressures are associated with poor prognosis in heart failure (HF). Invasive monitoring of LA-pressures and direct mechanical LA-decompression are associated with functional improvement in patients suffering from HF both with reduced and preserved ejection fraction. We aim to review the current available percutaneously implantable sensors for haemodynamic telemonitoring of LA-pressures (direct LAP sensor device-HeartPOD; right ventricular device-Chronicle; pulmonary artery device-CardioMEMs).

[Decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension]. / Dekompensierte Rechtsherzinsuffizienz, Intensiv- und Perioperativ-Management bei Patienten mit pulmonaler Hypertonie: 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 the targeted treatment of pulmonary arterial hypertension (PAH). 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 management of decompensated right heart failure, intensive care management and perioperative management in patients with pulmonary hypertension. This article summarizes the results and recommendations of the working group on decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension.

The first vector-graphics-aided computer tooth model and its animation.

Computer graphics is here to stay and spreading. This article intends to be nothing more than a brief introduction of this new tool in the field of dentistry. We hope that our colleagues will welcome this new development and recognize it as an opportunity to make contact with the basic sciences.

Species-specific autoantibodies in type 1 diabetes.

GAD65 autoantibodies (GAD65Ab) are important markers for type 1 (insulin-dependent) diabetes mellitus. Although most patients have GAD65Ab at the time of clinical diagnosis, there are also GAD65Ab-positive individuals in the population at low risk of developing type 1 diabetes. The aim of this study was to test the hypothesis that the GAD65Ab reactivity to GAD65 cloned from human, mouse, and rat in newly diagnosed type 1 diabetic patients differ from antibody-positive healthy individuals. Sera from 254 new-onset 0- to 34-yr-old type 1 diabetic patients and 270 controls were assayed for their reactivity to human, mouse, and rat GAD65. Among the type 1 diabetic patients there was a significant better binding of human GAD65 compared to either mouse (P = 0.03) or rat GAD65 (P = 0.0005). The preference for human GAD65 increased with increasing age at onset (P = 0.0002). This differentiation was not observed in 88 GAD65Ab-positive control subjects. Our data indicate that recognition of epitopes by GAD65Ab in type 1 diabetes is different from that in nontype 1 diabetes, GAD65Ab-positive individuals.

A simple and rapid microSepharose assay for GAD65 and ICA512 autoantibodies in diabetes. Diabetes Incidence Study in Sweden (DISS).

GAD65Ab and ICA512Ab are strongly associated with insulin-dependent (Type 1) diabetes mellitus. A novel, simple radio-antigen binding assay with microSepharose conjugated with monoclonal antibodies specific for human immunoglobulin light chains was developed to provide diagnostic sensitivity and specificity of GAD65Ab and ICA512Ab for Type 1 diabetes. The Receiver Operating Characteristic (ROC) curve was used to determine the upper level of Normal in 583 new onset Type 1 diabetic patients and in 829 matched controls. The sensitivity of GAD65Ab and ICA512Ab was 66% (384/583) and 41% (211/520), respectively, and the diagnostic specificity was 96% for both autoantibodies. Levels, but not frequency, of GAD65Ab were higher among female Type 1 diabetes patients, whereas ICA512Ab levels did not differ between males and females. Positivity for GAD65Ab. ICA512Ab or both showed a sensitivity of 74% and a specificity of 92% for Type 1 diabetes. This simple, one-step centrifugation, high-capacity radio-antigen binding assay has a high precision and reproducibility to accurately detect both GAD65Ab and ICA512Ab. This assay should also prove useful in other autoantibody assays against conformation-sensitive autoantigens.

The effect of nifedipine alone or combined with low dose acetylsalicyclic acid on endotoxin-induced pulmonary hypertension in the piglet.

Cardiovascular responses to the calcium antagonist nifedipine, alone and combined with low dose acetylsalicyclic acid (ASA), were evaluated in a piglet model of endotoxin-induced pulmonary hypertension. All animals were anesthetized, paralyzed and mechanically ventilated. Cardiac output (CO), pulmonary artery pressure (PAP), aortic blood pressure (SAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAPM) and arterial blood gases were measured before and after induction of pulmonary hypertension by E. coli endotoxin and after treatment. Results of treated groups were compared to a control group of piglets subjected to the same dose (0.15 micrograms/kg i.v.) of endotoxin. Control animals responded to a bolus injection of endotoxin within 15 min with an increase in mean PAP by 110%. Pulmonary vascular resistance (PVR) increased by 144%. Mean arterial pressure did not change significantly from baseline values. In animals treated with a single dose of 1 mg/kg ASA prior to endotoxin, the initial pulmonary response was not quantitatively different from control values, whereas ASA 20 mg/kg abolished the pulmonary vascular reaction. The increase of systemic vascular resistance (SVR) produced by endotoxin was aggravated by high dose ASA. In piglets treated with nifedipine (4 micrograms/kg/min) over 30 min after the application of endotoxin with and without additional infusion of nifedipine 60 min prior to endotoxin the PVR could be attenuated. The combination of nifedipine and low dose ASA showed synergistic effects compared to control. The increase of mean PAP was significantly reduced, the PVR remained in baseline range due to a marked elevation of cardiac output.

Continuous measurement of cardiac output by the Fick principle in infants and children: comparison with the thermodilution method.

OBJECTIVE: To compare a system that continuously monitors cardiac output by the Fick principle with measurements by the thermodilution technique in pediatric patients. DESIGN: Prospective direct comparison of the above two techniques. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: 25 infants and children, aged 1 week to 17 years (median 10 months), who had undergone open heart surgery were studied. Only patients without an endotracheal tube leak and without a residual shunt were included. METHODS: The system based on the Fick principle uses measurements of oxygen consumption taken by a metabolic monitor and of arterial and mixed venous oxygen saturation taken by pulse- and fiberoptic oximetry to calculate cardiac output every 20s. INTERVENTIONS: In every patient one pair of measurements was taken. Continuous Fick and thermodilution cardiac output measurements were performed simultaneously, with the examiners remaining ignorant of the results of the other method. RESULTS: Cardiac output measurements ranged from 0.21 to 4.55 l/min. A good correlation coefficient was found: r2 = 0.98; P < 0.001; SEE = 0.41 l/min. The bias is absolute values and in percent of average cardiac output was - 0.05 l/min or - 4.4% with a precision of 0.32 l/min or 21.3% at 2 SD, respectively. The difference was most marked in a neonate with low cardiac output. CONCLUSION: Continuous measurement of cardiac output by the Fick principle offers a convenient method for the hemodynamic monitoring of unstable infants and children.

Continuous monitoring of mixed venous oxygen saturation in infants after cardiac surgery.

Continuous mixed venous oxygen saturation (SvO2c) was measured in 16 infants immediately after cardiac surgery. A polyurethane 4F, dual channel catheter (Opticath, Modell U440, Oximetrix) with fiberoptic filaments was introduced into the pulmonary artery during cardiothoracic surgery. The catheters were left in place for an average of 67.5 h (range 27 h -125 h) and there were no catheter-related complications. Correlation between continuous in vivo SvO2 values and in vitro values was satisfactory (r = 0.85), whereas a correlation between SvO2c and arterial oxygen saturation (SaO2) was not found (r = 0.07). The sampled arterial lactate values were inversely correlated to the simultaneously measured SvO2c, but the correlation coefficient was only r = -0.4. There was an inverse correlation between SvO2c and arteriovenous oxygen content difference (Ca-vDO2) (r = -0.82), and a marked inverse correlation to the calculated oxygen utilization ratio (r = -0.97). Therefore SvO2c continuously reflects the overall balance between oxygen consumption and delivery, but the use of SvO2 as a predictor of blood lactate levels is unreliable. A further purpose of the present study was to demonstrate the clinical applications and to show the usefulness of SvO2c-monitoring; particularly as a surveillance and early warning system, as a guide for assessing therapy and its relevance in interpreting other monitored parameters. In our opinion continuous SvO2 measurement is a reliable and valuable indicator of cardiopulmonary function in the immediate post-operative period, even in infants with complicated repair of cardiac malformations.

Reduced inotropic support after aprotinin therapy during pediatric cardiac operations.

BACKGROUND: Several reports indicate that aprotinin treatment before and during cardiopulmonary bypass (CPB) might have a protective effect on the myocardium. We evaluated the hemodynamic effects of perioperative aprotinin treatment. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 34 infants (mean age, 2.5 years) who had cardiac operations. Half of the patients received high-dose aprotinin therapy. There were no significant differences between the aprotinin and placebo groups with respect to age, weight, sex, aortic cross-clamp time, and CPB time. The following data were recorded at arrival in the intensive care unit 6, 12, 24, and 48 hours after termination of CPB: heart rate, blood pressure, left atrial pressure, central-peripheral temperature difference, arterial-central venous oxygen saturation difference, urine output, serum creatinine, lactate and neutrophil elastase levels, the Doppler echocardiographic factors shortening fraction and preejection period/left-ventricular ejection time, and cumulative doses of catecholamines (epinephrine), enoximone, and furosemide. RESULTS: No hemodynamic variable showed any significant difference between aprotinin and placebo groups. Urine output, creatinine, lactate, and elastase levels, as well as the cumulative doses of furosemide and epinephrine were not significantly different. Twelve hours after CPB 10 patients in the placebo group and 4 in the aprotinin group had received enoximone (p<0.05). The placebo group had received significantly larger doses of enoximone than the aprotinin group at arrival in the intensive care unit (0.13+/-0.05 versus 0 mg/kg), 12 hours after CPB (0.58+/-0.14 versus 0.18+/-0.09 mg/kg), 24 hours after CPB (1.11+/-0.24 versus 0.42+/-0.16 mg/kg), and 48 hours after CPB (1.61+/-0.40 versus 0.86+/-0.28). At 6 hours the difference did not reach statistical significance. CONCLUSIONS: Clinical and hemodynamic status of the aprotinin-treated patients was similar to that of the placebo-treated patients in the first 48 hours after CPB. The placebo group, however, required significantly more inotropic support by enoximone than the aprotinin group to achieve this goal.

Percutaneous closure of secundum atrial septal defect with a new self centering device ("angel wings").

OBJECTIVE: To investigate the safety, efficacy, and clinical application of a new self centering device ("angel wings") for closure of secundum atrial septal defects (ASD II) and persistent foramen ovale in all age groups. DESIGN: Multicentre, prospective, nonrandomised study. INCLUSION CRITERIA: defects with an occlusive diameter of < or = 20 mm and a surrounding rim of > 4 mm; body weight > 10 kg; and an indication for surgical closure of secundum atrial septal defect. Additionally, there were compassionate indications for closure in patients with persistent foramen ovale. INTERVENTIONS: Defects were closed by a transcatheter device consisting of two square frames made of superelastic nitinol wire. The frames are covered by elastic polyester fabric, which is sewn together at a central circle. All procedures, except for three interventions that were carried out under sedation, were performed under general anaesthesia using transoesophageal echocardiography and fluoroscopy to monitor intervention. RESULTS: Closure was attempted in 75 (71%) of 105 patients. An ASD II was present in 35 children and 15 adults. A persistent foramen ovale was present in 25 adults with suspected paradoxical embolism. Transcatheter closure was unsuccessful in three children and crossover to surgery was required. Residual shunts were found in 20 patients (27%) immediately after the procedure. A transient atrioventricular third degree block occurred in three patients (4%) and the right atrial disk was not fully deployed in three. A minor shunt (< 3 mm) was present in only three (4%) of 72 patients during follow up of 1-17 months. Blood clots on the right atrial disks in two patients (one required lysis) were seen during follow up transoesophageal echocardiography. Serious complications demanding surgical removal of the device occurred in three patients. One patient had haemopericardial tamponade because of an aortic lesion. Left atrial thrombus formation due to an unfolded right atrial disk was found in a second patient and dislodgement of the left atrial disk resulted in a large residual shunt in a third. CONCLUSIONS: Percutaneous closure of a central ASD with a diameter < or = 20 mm in paediatric and adult patients is feasible and effective with this new device. It is a promising alternative to surgical closure. Modifications of the design, however, seem to be mandatory as 4% of patients developed serious complications.

GAD65 and IA-2 autoantibodies are common in a subset of siblings of Sardinian Type 2 diabetes families.

UNLABELLED: Type 1 diabetes in Sardinia is very common in children, and we hypothesized that Latent Autoimmune Diabetes of Adult (LADA) might constitute a significant proportion of diabetes in adult Sardinian subjects. Since Type 2 diabetes is a familial disorder, we tested this hypothesis by investigating the prevalence of GAD65 and IA-2 autoantibodies (Ab) in Type 2 diabetes multiplex families of Sardinian ancestry enrolled in the Study Group for the Genetics of Diabetes in Sardinia. METHODS: A total of 684 individuals were ascertained from 252 Sardinian Type 2 diabetes multiplex families with 2.4 affected siblings per family comprising 190 families with two affected, 37 with three, 15 with four, 7 with five, and 3 with six, in addition to 80 unaffected siblings. Controls were household contacts representing 204 healthy spouses of affected siblings. Diagnosis was at 35-69 years of age and insulin was not given in the first 4 years after diagnosis. GAD65Ab and IA-2Ab were determined in standard radioligand binding assays. RESULTS: Among affected siblings GAD65Ab were positive in 8.8% of insulin-treated (n = 137; P = 0.0006), in 2.5% of non-insulin-treated (n = 467), and in 1.2% of non-diabetic siblings (n = 80) compared with 0.5% of controls (n = 204). IA-2Ab was positive in 6.6% insulin-treated (P = 0.04), 2.1% non-insulin-treated, and 2.5% non-diabetic siblings compared with 1.5% of controls. CONCLUSION: A high frequency of GAD65Ab and IA-2Ab as markers of Type 1 diabetes was found among Type 2 diabetes siblings from Sardinian multiplex families despite excluding those who had been treated with insulin during the first 4 years of disease. Our data support the hypothesis that LADA may be common in Sardinian Type 2 diabetes and stress the importance of investigating markers of Type 1 diabetes in studies of Type 2 diabetes.

Clinical experience with heart transplantation in infants.

OBJECTIVE: Orthotopic heart transplantation has become an accepted therapeutic concept for adult patients with endstage heart disease. In newborns and infants this procedure is still a matter of discussion because of unknown long-term results and the lack of donor organs. METHODS: Since March 1988 we have performed 40 orthotopic heart transplantation in 39 infants who were from 1 to 280 days of age. Indications for transplantation included hypoplastic left-heart syndrome (n = 28), dilative cardiomyopathy (n = 4), endocardial fibroelastosis (n = 4) and other complex structural anomalies (n = 3). The mean waiting period for transplantation was 53 days. A donor-recipient weight ratio up to 4.0 was accepted. Profound hypothermic circulatory arrest was used for graft implantation in all those patients who required extensive aortic arch reconstruction (71%). The initial immunomodulation was based on Cyclosporine, Azathioprine and Prednisolone. Patients who underwent transplantation during the first 6 weeks of life received a chronic single-drug therapy with Cyclosporine after 1 year. RESULTS: There were six peri-operative deaths caused by drug-resistant right-heart failure in three cases, humoral rejection (n = 1), CMV infection (n = 1) and multi organ failure (n = 1). One infant died late, due to rejection. The actuarial survival rate for the entire group is now 82%. There is a remarkable influence of increasing experience. Whereas six of 15 infants who had heart transplantation between 1988 and 1993 died early post-operatively (survival rate: 60%), only one late death occurred among 24 recipients in the period from 1994 to April 1997 (survival rate: 96%). Episodes of rejection occurred once or several times in about half of the patients in this series (48%). All surviving children are living at home in excellent condition. CONCLUSIONS: Heart transplantation during early infancy is a rational and durable therapy for heart diseases with irreversible myocardial failure or severe structural anomalies. The intermediate-term results have been encouraging in many centers, but more data must be accumulated to determine the sequelae of chronic immunosuppression. The lack of donor organs remains one of the major problems in pediatric heart transplantation.