Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.

Normal values for noninvasive estimation of left ventricular contractile state and afterload in children.

The outcome and suitability for therapeutic interventions in children with congenital heart disease depend frequently on left ventricular function. Congenital heart disease is characterized by changes in loading conditions, making it difficult to assess ventricular contractility using conventional load-dependent indexes. Two-dimensional and M-mode echocardiography and arterial blood pressure were used to study left ventricular morphometrics and contractility in 44 normal children, aged 2 to 12 years. Left ventricular end-systolic and end-diastolic length, diameter, wall thickness, volume and mass all showed linear increases with body surface area (p less than 0.001 in all). Shortening and ejection fractions, velocity of circumferential fiber shortening, morphometric ratios and endocardial meridional and circumferential stress (mean 46 and 115 g/cm2, respectively) all remained constant. A load-independent measure of the normal resting left ventricular contractile state was determined by relating the rate-corrected velocity of circumferential fiber shortening to end-systolic endocardial meridional and circumferential stress; there was an inverse linear correlation (r = -0.641 and -0.557 respectively, p less than 0.001). These data provide a quantitative basis for assessment of myocardial hypertrophy, afterload and contractile state in childhood.

Is ventricular arrhythmia in repaired tetralogy of Fallot an effect of operation or a consequence of the course of the disease? A prospective study.

Ventricular arrhythmia is common after repair of tetralogy of Fallot. Such arrhythmia could be caused by damage at surgical repair or it could be part of the course of the disease. Fifty patients, 32 aged 1-7 years and 18 aged 13-43 years at surgical repair, underwent 24 hour electrocardiographic monitoring before and 2-75 (mean 44) months after repair. Before operation none of the younger group had appreciable ventricular arrhythmia, whereas ventricular arrhythmia was already present in eight (45%) of 18 patients in the older group. At follow up ventricular arrhythmia was present in four patients from the younger group and seven from the older group. Three of these four younger patients had had insertion of a conduit from the right ventricle to the pulmonary artery or reoperation. Six of the seven older patients had had appreciable ventricular arrhythmia before operation. New ventricular arrhythmia developed in only two (5%) of the 43 patients who had uncomplicated repair of tetralogy of Fallot. Thus the high frequency of ventricular arrhythmia after repair of tetralogy of Fallot cannot be attributed to the effect of operation alone because in the majority of patients it was already present before operation. Preoperative ventricular arrhythmia occurred almost exclusively in older patients; this suggests that early surgery may reduce the occurrence of this late complication.