Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.

The German twin family study ‘TwinLife’ was designed to enhance our understanding of the development of social inequalities over the life course. The interdisciplinary project investigates mechanisms of social inequalities across the lifespan by taking into account psychological as well as social mechanisms, and their genetic origin as well as the interaction and covariation between these factors. Main characteristics of the study are: (1) a multidimensional perspective on social inequalities, (2) the assessment of developmental trajectories in childhood, adolescence, and young adulthood in a longitudinal design by using (3) a combination of a multi-cohort cross-sequential and an extended twin family design, while (4) capturing a large variation of behavioral and environmental factors in a representative sample of about 4,000 German twin families. In the present article, we first introduce the theoretical and empirical background of the TwinLife study, and second, describe the design, content, and implementation of TwinLife. Since the data will be made available as scientific use file, we also illustrate research possibilities provided by this project to the scientific community.

Cross-sectional echocardiography was performed on 108 healthy children (7 days – 17 years old) and 55 children (6 months - 16.5 years old) with interatrial communication. Right ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, muscle volume, and the ratio of muscle to cavity were calculated on the basis of outlined cavity and myocardium of an apical fourchamber view.

In the normal subjects right ventricular end-diastolic volume, end-systolic volume, stroke volume and muscle volume correlated with body surface area (end-diastolic volume: y=12.5x+7.8x2, r=0.99; end-systolic volume: y=4.8x+3.6x2, r=0.98; stroke volume: y=7.7x+4.2x2, r=0.98; muscle volume: y=14.1x+2.9x2, r=0.97), muscle/cavity ratio (0.85±0.17) and ejection fraction (58.9 ± 6.2%) were unrelated to body surface area. In the subjects with interatrial communication, the right ventricular volumes were significantly larger (p<0.001) than the normal values with a linear relationship to the ratio of pulmonary to systemic flows.

Right ventricular volumes can be determined in normal children with acceptable repeatability using a standard apical four-chamber view. The growth related normal values provide a basis for future quantitative studies.

Assessment of right ventricular volume and function is important in most congenital heart diseases before and after corrective or palliative surgery. Since transthoracic echocardiography is often substituted by transesophageal echocardiography in the perioperative setting, it is useful to compare transesophageal echocardiography with transthoracic echocardiography as performed preoperatively. We compared right ventricular volumes as calculated using these two methods from a four-chamber view in 21 children and adults with atrial septal defect. For right ventricular end-diastolic volumes of less than 70 ml, and end-systolic volumes of less than 40 ml, a close correlation was found between the techniques (r=0.99 and r=0.91, respectively), with a small degree of underestimation by transesophageal echocardio­graphy. For values larger than 70 nil and 40 ml, respectively, correlation decreased (r=0.41 for end-diastolic volumes and r=0.48 for end-systolic volumes) and underestimation of volume by transesophageal echocardiography increased. Underestimation of right ventricular end-diastolic volumes increased with increasing body surface area (r=0.74), and with progressive right ventricular enlargement (r=0.63). In patients with a body surface area of more than 1m2, the largest end-diastolic right ventricular length determined by transthoracic echocardiography was significantly longer than that derived by transesophageal echocardiography (p<0.001), whereas in smaller patients there was no significant difference between the two methods (p>0.1). If right ventricular volumes determined by transthoracic echocardiography using a four-chamber view are substituted by those obtained with transesophageal echocardiography in serial haemodynamic evaluation of patients with atrial septal defect, different correlation equations and, consequently, a different degree of underestimation by transesophageal echocardiography must be considered for large and small volumes. This increasing underestimation of larger right ventricular volumes seems to be based on foreshortening of the long cross-sectional axis of the right ventricle as seen in the transesophageal four-chamber view.

To judge whether an Amplatzer™ Septal Occluder can be used as standard therapy instead of surgery for closure of atrial septal defects we report our experiences in 200 patients. Of these patients, 127 had an atrial septal defect with haemodynamically significant left-to-right shunt, 68 patients a persistent oval foramen after presumed paradoxical embolism, and 5 had a fenestration after Fontan-repair. Mean age was 29.8 years (0.8 to 77.7 years). Body weight ranged from 6.9 to 120.0 kg (mean 51.5 kg). After diagnostic cardiac catheterization, and balloon-sizing of the defect, we implanted Amplatzer™ Septal Occluders with stents of 4 to 28 mm diameter. Follow-up studies were obtained after 48hours, and one, six, and twelve months. Transcatheter closure of the atrial septal defect proved successful in all without any relevant residual shunts. In particular, complete closure was achieved in all patients after presumed paradoxical embolism. The mean period of follow-up is 9–5 months, with a range from 0.4 to 23.5 months, giving a total of 1898 patient months. The occlusion rate after three month was 98.1°. A trivial haemodynamically insignificant residual shunt remained in 1.9° of the patients. Fluoroscopy times ranged from 0 to 43.5 minutes, with a median of 8.7 minutes. The excellent results in the short and medium term in children and adults have resulted in using this device routinely at the present time for closure of central atrial septal defects up to a diameter of 28 mm. Final judgement, however, is only possible after long-term follow-up.

Background: Stenting for aortic coarctation has been shown to be effective in the short term. The safety and longer term efficacy of transcatheter therapy, however, must be well established if the technique is to be widely accepted as an alternative to surgery. In order to determine the frequency, spectrum, and outcome of injury to the aortic wall caused by angioplasty or stenting of aortic coarctation, the nomenclature of mural injury in these patients must be adapted to the conditions of transcatheter therapy. Methods and Results: Between 1989 and July 2005, we inserted stents in 153 patients with aortic coarctation, their median age being 15.8 years. Prior aortic interventions had been performed in 98 patients, and preexisting aneurysms were observed in 19. Stenting resulted in a significant reduction of the gradient across the site of coarctation, from a median of 30 millimetres of mercury to zero (p less than 0.001), with a residual gradient within the aortic arch of 20 millimetres of mercury or more in 5% of patients. Acute injuries to the aortic wall, other than therapeutic tears, were observed in 3 patients (2%), none of whom required surgery. At median follow-up of 2.5 years, this being more than 5 years in 30 patients, 4 patients had died, albeit none from complications relating to stenting or catheterization. Acute injuries to the aortic wall did not progress, and new aneurysms were observed in 6% of patients subsequent to follow-up imaging. Stent fractures, and jailed or partially covered brachiocephalic vessels, were observed in 12, and 49, patients, respectively, but did not result in haemodynamic or embolic complications. Conclusions: Stenting for aortic coarctation results in consistent relief of the gradient, and few serious complications in the short and intermediate term. Serious injuries to the aortic wall are uncommon in our experience, and can be minimized with a focus on technical measures, such as pre-dilation before stenting.

Background: Multiple perforations in the floor of the oval fossa may be an obstacle for transcatheter closure. Thus, we analyzed the interventions in 33 patients with more than one interatrial communication in comparison with 370 procedures with a single defect. Methods and Results: A diagnostic catheterization, which included a balloon-sizing maneuver, was performed. We implanted a total of 46 occluders, made up of 42 Amplatzers and 4 CardioSEALs. In 20 patients, the defects were closed with a single occluder, namely 18 Amplatzer and 2 CardioSEAL devices. Complete closure was achieved in 15 patients, while a tiny residual shunt remained in 5 patients. In 13 patients, two devices were implanted, without any residual shunt being found immediately after implantation. In 3 patients, the occluders did not touch each other. In 10 patients, their rims overlapped. In comparison with the control group, the group with multiple defects did not differ in the distribution of age, gender, and indications for device closure. The mean time of the procedure, and the time required for fluoroscopy, however, were significant longer (P< 0.001). These times ranged from 45 to 250 minutes with a median of 140 minutes, and from 0.0 to 39.2 minutes, with a median of 12.0 minutes, respectively. Also, the association with an atrial septal aneurysm was significantly more frequent 61 vs. 17%; P< 0.001). The times taken during insertion of double devices were also significantly longer than those needed for insertion of a single device (P< 0.001). Conclusions: Transcatheter closure of multiple defects within the oval fossa is feasible with currently available occluders, albeit than, in selected cases it is necessary to implant two devices.

Background: Acute renal failure is an occasional complication after cardiopulmonary bypass in infants. Whereas it is well known that postoperative hemodynamics inflict acute renal failure, the influence of extra-corporeal circulation on the kidney is less clear. Moreover, changes in blood viscosity occur during and after surgery, which may influence renal dysfunction. For this reason, we investigated the impact of blood viscosity on renal function during cardiopulmonary bypass. Methods: In 34 patients weighting less than 10 kg, we performed repeated analysis of urine, blood, and plasma viscosity. Results: Polyuria and proteinuria that appeared during cardiopulmonary bypass indicated an elevated transglomerular filtration gradient, which recovered within 24 hours. The appearance of N-acetyl-β-D-glucosaminidase in the urine, and elevated excretion of sodium, were additionally indicative of mild tubular damage. Elevation of blood viscosity during hypothermic perfusion showed a statistical correlation with proteinuria and N-acetyl-β-D-glucosaminidaseuria. With hypothermia, the relation of blood viscosity to plasma viscosity became stronger, while the relation to the hematocrit decreased compared to normothermia. Conclusions: During cardiopulmonary bypass perfusion, the kidney can be stressed by proteinuria and mild tubular damage. Our data provide evidence that the kidneys can be protected by improved blood viscosity during cardioplegia, but this needs confirmation in a prospective interventional study.

We aimed to assess the right atrial performance in patients after surgical correction of tetralogy of Fallot, and to clarify the relationship between the pump function of the right atrium and right ventricular systolic function.

We included in the study 50 asymptomatic patients following corrective surgery of tetralogy of Fallot, comparing them to 30 normal subjects. Right atrial areas were measured by echocardiography, and the active fractional area of emptying was expressed, in percentages, as the area measured at the onset of atrial contraction, minus the minimal area, divided by the area at the onset of atrial contraction. We used this value to assess the atrial pump function. Right atrial peak strain rates were measured by tissue Doppler imaging. Compared to controls, patients with tetralogy of Fallot had a significantly reduced right atrial active fractional area of emptying (p = 0.005), along with a reduced peak late diastolic strain rate (p = 0.002). Among 20 patients who underwent magnetic resonance tomographic examination, a relatively higher right atrial peak late diastolic strain rate was shown in patients with a right ventricular ejection fraction of less than 50% (p = 0.021).

Right atrial performance is reduced in patients after surgical correction of tetralogy of Fallot. When facing right ventricular systolic dysfunction, nonetheless, the right atrial pump function may be relatively enhanced. Tissue Doppler derived strain rate can provide quantitative analysis of regional right atrial performance.