What is a shunt? Concepts of central shunts and effective flow and a method for graphical presentation of circulatory quantities and their interrelations.

The terminologies commonly used in descriptions of abnormal patterns of blood flow in patients with congenital heart defects are valid only in the case of simple abnormal communications in an otherwise essentially normal cardiac anatomy. In more complex cases the expressions are unambiguous and elucidatory only when qualified further, but then the terminology becomes cumbersome. Much might be gained in clarity by considering the combined ventricular output as having four components: two are essential, and equal in size; they constitute the effective flows to the systemic and pulmonary arterial trees of blood from the pulmonary and systemic veins, respectively. The other two are recirculated systemic and pulmonary flows and may or may not exist; they may be referred to as blue and red shunts, respectively. Here, 'shunt' is defined as a by-pass of the capillary system to which a given blood flow is destined. The red and blue shunts are both central--as distinct from peripheral ones, where the by-pass links arteries and veins in one of the two circulations. Adoption of the concepts of central shunts and effective flow as defined here would facilitate a rational and consistent quantitative analysis of the circulation in individual cases irrespective of variations in cardiac anatomy. It would also make it possible to present in instantly understandable diagrams the magnitudes and interrelations of such variables as the oxygen consumption, the blood's oxygen capacity and the oxygen contents of the blood in the great vessels connecting the heart and the two circulations, the combined ventricular output and its components, the mean pressure difference across the pulmonary circulation and the pulmonary vascular resistance. A graph blank for such a presentation is proposed, and its application in cases with and without central shunts is exemplified.

Total anomalous pulmonary venous connection in siblings. Report on three families.

Three pairs of siblings with total anomalous pulmonary venous connection (TAPVC) are reported. The types of the anomalous venous return (supra- or infracardial connections) varied within the families indicating that genetic regulation deals with the left atrial connection to the intrapulmonary veins. Having failed to establish this connection the intrapulmonary veins can attach themselves to any adjacent venous structure; hence the variety of connections at birth. Our observations also indicate the possibility that specific genetic mechanisms operate in at least some families. Since signs, such as murmurs and cardiomegaly typical of a cardiac anomaly, are not always present in TAPVC, special attention should be paid to any neonatal abnormality in siblings of known cases with TAPVC.

Ventricular dynamics after surgical closure of VSD.

Twenty patients varying in age between 5 and 20 years at the time of surgical closure of VSD were studied 2 to 9 years postoperatively. Ventricular function was studied by echocardiography and measurement of systolic time intervals for the left and right ventricles and the findings were related to clinical and haemodynamic results of operation. The VSD was closed in all instances and the haemodynamic situation was normalized in all but 2 patients who had persisting pulmonary vascular disease. Right bundle branch block (RBBB) was recorded in 11 instances and in 5 there was an associated left axis deviation (LAD), suggesting left anterior hemiblock. LAD occurred as an isolated anomaly in another 2 patients. The heart size was within normal limits in all the patients. Abnormal septal motion (ASM) was recorded in 13 of the 20 patients, but other echocardiographic analyses, such as LV end-diastolic dimension, left atrial/aortic root ratio, posterior wall velocity index and maximal endocardial velocity, were all within predicted normal limits. There was an almost uniform prolongation of both left and right pre-ejection periods. left and right ejection period as a rule remained normal and gave an increased PEP/ET ratio, indicating the presence of postoperative ventricular dysfunction also in instances with complete normalization of the haemodynamic situation. Suggested background mechanisms for these findings are the frequent occurrence of conduction defects postoperatively, the likelihood of altered ventricular compliance and possibly also as a cause of ASM postoperative presence of an opened pericardial sac.

Noonan syndrome with café-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus.

Noonan syndrome, multiple lentigines syndrome (LEOPARD syndrome), Watson syndrome and neurofibromatosis type 1 share certain clinical manifestations. We present a linkage analysis using microsatellite markers located in the neurofibromatosis type 1 region at 17q11 in a family with Noonan syndrome and café-au-lait spots and in another family with multiple lentigines syndrome. No linkage of the disease to the neurofibromatosis type 1 locus was found in the families investigated. On the basis of our results, we suggest that neither familial multiple lentigines syndrome nor Noonan syndrome is caused by a defect in the neurofibromatosis type 1 gene.

V. Exercise studies in children with congenital heart disease. An earpiece densitometric investigation.

Twenty-three patients have been studied by exercise testing during right heart catheterization. Cardiac output was measured by the earpiece densitometric technique before, during and after the exercise period. It is concluded that the earpiece densitometric technique in conjunction with exercise testing offers an attractive alternative for the study of pressure and flow characteristics in children with congenital heart disease.

II. Cardiac output studies in infants and children undergoing right heart catheterization.

Cardiac output figures from 97 patients were computed by earpiece densitometry and correlated to various dimensional parameters. Stroke volume was better correlated to body dimensions than cardiac output indicating that patients undergoing right heart catheterization were not in basal state.

IV. Evaluation of dichromatic earpiece densitometry in children with left-to-right shunts.

Earpiece densitometry was performed in 60 infants and children with left-to-right cardiovascular shunts. The method was found to possess a high diagnostic sensitivity with respect to identification of the left-to-right shunt. Earpiece densitometry was in this respect clearly superior to conventional method using oxygen saturation figures. Quantitation of pulmonary blood flow by both densitiometric and oxygen content technique in a small number of patients indicates that the dye dilution technique gives values somewhat in excess of the Fick method. It is concluded that quantitation of the magnitude of the left-to-right shunt and pulmonary blood flow is disturbed by the fact that indicator material is recirculated before the ascending limb of the primary curve is fully inscribed.

Clinical experience of pacemaker treatment in children.

Pacemaker treatment is more complicated in children than in adults, mainly because of electrode problems. A pacemaker system was implanted in 23 children aged 2 days-14 years (mean 4.8 years, with 11 less than or equal to 3 years) at the Karolinska Hospital since 1983. The indications for pacing were peroperative atrioventricular block (AVB) in 13 cases, congenital AVB in five, sinoatrial disorder in four and slow ventricular arrhythmia in one case. The initially implanted electrode was epicardial in ten children (in the first 2 years of the study) and endocardial in the other 13. Eight of the ten epicardial electrodes had to be replaced by endocardial within a mean of 2.5 years. There were 18 reoperations, the reasons being increased threshold/exit block--all epicardial leads (8 cases), electrode failure (1), 'stretching' of the electrode secondary to body growth (4), local infection (3) and generator replacement (2). The reoperation rate was unacceptably high in children with epicardial electrodes. Endocardial pacing is the method of choice even for small infants.

I. Validity of dichnomatic earpiece densitometry for quantitative studies in children with shunt-free cardiovascular malformations.

Cardiac output was assessed in 16 children without evidence of cardiovascular shunts from simultaneously recorded earpiece and cuvette densitometric tracings. The earpiece set-up was calibrated by the end-tail method. Both instruments gave linear response to dye concentrations used. There was a close correlation between cardiac output figures recorded by the two methods (r equal to 0.95) and no systematic difference occurred. It is concluded that in infants and children earpiece densitometry constitutes a rapid and accurate method for quantitative circulatory studies.

The "cat eye syndrome": dicentric small marker chromosome probably derived from a no.22 (tetrasomy 22pter to q11) associated with a characteristic phenotype. Report of 11 patients and delineation of the clinical picture.

Eleven patients with the so-called Cat Eye syndrome are reported including a more detailed description of the original cases reported by Schmid and Fraccaro. All cases had, in addition to a normal karyotype, a small extra G-like chromosome which appeared to be an isochromosome for the juxtacentromeric region (pter to q11) of an acrocentric chromosome. None were mosaics. Clinical findings and further cytogenetic studies in a few cases suggest that these markers probably derive from a No. 22 chromosome. Characteristic features of the Cat Eye syndrome in these 11 patients and those reviewed from the literature are: ocular coloboma which may involve the iris, choroid and/or optic nerve, preauricular skin tags and/or pits which are probably the most consistent feature, congenital heart defect, anal atresia with a fistula, renal malformations such as unilateral absence, unilateral or bilateral hypoplasia, and cystic dysplasia, and antimongoloid position of eyes. Intelligence is usually low-normal, although moderate retardation is also seen. There is great variability in the clinical findings ranging from near normal to lethal malformations. Less frequent, but also characteristic findings are: microphthalmia, microtia with atresia of the external auditory canal, intrahepatic or extrahepatic biliary atresia and malrotation of the gut. Direct transmission of the marker from one generation to the other was observed in both sexes. In those families, there was considerable variability in the clinical findings between affected family members. These cases show that there is a bias of ascertainment for patients who have the more striking malformations, especially those with ocular coloboma and anal atresia, a combination which appears to be present in only a minority of cases. Many mildly affected patients probably remain undetected. It is proposed that the term Cat Eye syndrome should be applied only to cases with trisomy or tetrasomy of not more than 22pter to q11 and without additional duplication or deletion of another autosomal segment.

Investigation of deletions at 7q11.23 in 44 patients referred for Williams-Beuren syndrome, using FISH and four DNA polymorphisms.

Williams syndrome (WS) is associated with a submicroscopic deletion of the elastin gene (ELN) at 7q11.23. The deletion encompasses closely linked DNA markers. We have investigated 44 patients referred for possible WS using fluorescence in situ hybridization (FISH) analysis with a P1 clone containing an insert from the ELN, as well as performing genotype analysis of patients and parents with four DNA polymorphisms. Twenty-four patients were found to have deletions, 19 of whom were found clinically to have typical WS. The facial features were especially characteristic. None of the patients without detectable deletions was reported to have typical WS features, although one had supravalvular aortic stenosis, hypercalcemia, and mental retardation. No evidence was found in this material for variability of the size of the deletion. Our study supports the usefulness of analysis of ELN deletion in WS patients, both for confirmation of diagnosis and for genetic counselling.