[Percutaneous transluminal embolization of pulmonary arteriovenous malformations]. / Perkutan transluminal embolisation af pulmonale arteriovenøse malformationer.

OBJECTIVE: The aim was to evaluate the effect of embolisation of pulmonary arteriovenous malformations (PAVM), as estimated by contrast echocardiography, arterial blood-gas analyses and functional level, and further to evaluate procedure-related and late complications. PATIENTS AND METHODS: Seventeen patients were treated on 25 occasions for a total of 48 PAVM. Fifteen patients had hereditary haemorrhagic telangiectasia (HHT). Chest X-ray, pulmonary angiography, contrast echocardiography, arterial blood-gas analyses, and functional level were analysed before and after embolisation of PAVM. The mean follow-up period was 22 months. RESULTS: Contrast intensity at contrast echocardiography decreased from median 4.0 (range 2-4) before embolisation to 1.5 after embolisation. PaO2 breathing 100% oxygen increased from mean 271 mm Hg before embolisation to 480 mm Hg after embolisation. The shunt was reduced from mean 24% before to 12% after embolisation. Most of the patients experienced an increased functional level after embolisation, and the median functional level (NYHA) increased from NYHA 2.5 to 1.2. No primary or secondary device migration, no cerebral insults, and no mortality was noted. CONCLUSION: Embolisation is a well-established method of treating PAVM, with a significant effect on oxygenation of the blood. It is a minimally invasive, lung-preserving treatment with high affectiveness and low morbidity and mortality. Patients with HHT should be screened for PAVM as a high percentage of these have PAVM.

Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT).

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease. HHT is characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. OBJECTIVE: To estimate (i) the prevalence of PAVM, and (ii) the occurrence of neurological symptoms in a geographical well-defined population of HHT patients. METHODS: HHT family members were invited to a clinical examination including registration of HHT manifestations, screening for pulmonary arteriovenous malformations and neurological evaluation. Two groups served as controls: (i) first-degree relatives without any signs of HHT; and (ii) age- and gender-matched controls. SETTING: Odense University Hospital. SUBJECTS: HHT patients identified in a cross-sectional family survey carried out in the County of Fyn, Denmark. RESULTS: Included in the study were 169 HHT family members representing 24 families. They included both HHT patients and their first-degree relatives. The criteria of HHT were fulfilled in 75 participants; of these, 59 had a screening procedure performed, and PAVMs were demonstrated at pulmonary angiography (PA) in 18. Seven of the HHT patients had a history of cerebral stroke, compared with none of their healthy first-degree relatives. CONCLUSION: The prevalence of PAVM was 24% amongst HHT patients. The study confirmed an increased prevalence of neurological symptoms amongst HHT patients; the odds ratio was estimated to be 7.6. In order to enable prevention of these complications, screening for PAVM should become an integral part of the medical care for HHT patients.

Screening for pulmonary arteriovenous malformations: contrast echocardiography versus pulse oximetry.

Pulmonary arteriovenous malformations (PAVM) cause right-to-left shunt and imply risk of paradoxical embolism and cerebral abscess. These complications can be prevented by appropriate treatment. Detection of PAVMs is therefore important, so simple and reliable screening methods are needed for this purpose. The aim of this investigation was to compare pulse oximetry and contrast echocardiography as screening tools for detection of pulmonary arteriovenous malformations. Eighty-five hereditary haemorrhagic telangiectasia (HHT) patients and first-degree relatives identified in a comprehensive study of HHT-families in the county of Funen, Denmark, were investigated. Standing and supine pulse oximetry in room air was performed in all subjects, and in subjects with symptoms and/or abnormal pulse oximetry in room air, supine pulse oximetry breathing 100% oxygen was also performed. Transthoracic echocardiography with intravenous injection of echo contrast was performed in all subjects. Outcome measures were oxygen saturation change >2% units on changing body position and echo contrast observed in the left-sided heart chambers. Positive contrast echocardiography indicating the presence of PAVM was found in 47 subjects, whereas pulse oximetry was abnormal in only 16. The results strongly suggest that contrast echocardiography is a more sensitive screening tool for PAVMs than pulse oximetry.

Changes in cardiac muscle mass and function in hemodialysis patients during growth hormone treatment.

BACKGROUND: Adult patients with chronic renal failure (CRF) often show symptoms as fatigue, wasting, and reduced working capacity with concomitant findings of reduced cardiac performance and muscle mass. This state may in part be caused by an imbalance in the somatostatin/somatomedine axis resulting in increased catabolism. During an attempt to correct this catabolic state by administration of exogenous growth hormone, cardiac muscle mass and performance were studied. METHODS: In a double-blind, placebo-controlled 6-month study comprising 20 adult enfeebled hemodialysis patients, 9 patients were treated with a single daily subcutaneous injection of recombinant human growth hormone (rhGH) 4 IU/m2 and 11 with placebo injections. Left ventricular muscle mass (LVM) and ejection fraction (EF) were evaluated by echocardiography and the maximal working capacity (MWC) was measured by a bicycle exercise test performed before and after the treatment period. Supplementary electrocardiography (ECG) was performed before and after 6-month treatment. RESULTS: Median LVM increased significantly from 172 to 220 g (p = 0.03) in the rhGH-treated group, while an insignificant decrease was observed in the placebo group from 281 to 200 g (p = 0.3). The EF showed no significant changes in the two groups. MWC showed a slight, insignificant decrease in both groups. From ECG no significant ST deviations were found and no significant changes regarding B-Hb, blood pressure or pulse were observed in the two groups. Irregular heart rhythm aggravated in one patient during the first month of treatment with rhGH, but was overcome by a -blocking agent. CONCLUSION: The treatment with rhGH of adult chronic hemodialysis patients for 6 months increased the left ventricular mass significantly, but without any effect on ejection fraction or maximal working capacity. No electrocardiographic signs of ischemia were associated with the increasing muscle mass and only one patient developed symptoms that might relate to ischemia. No changes in B-Hb, blood pressure or pulse were observed during the treatment period.

Pulmonary arteriovenous malformations: screening procedures and pulmonary angiography in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited disease with a high prevalence of pulmonary arteriovenous malformations (PAVMs). The first symptom of HHT may be stroke or fatal hemoptysis associated with the presence of PAVM. OBJECTIVE: To evaluate different screening methods applied for the identification of PAVMs. SETTING: Odense University Hospital. SUBJECTS: HHT patients with positive findings on contrast echocardiography (CE) who participated in a screening investigation and underwent pulmonary angiography (PA). METHODS: Different screening methods were evaluated against the results of PA. In a group of patients with positive findings on CE, we compared results of PA with the following: severity of dyspnea; results of pulse oximetry arterial oxygen saturation (SaO2) supine and upright; supine PaO2 in room air and while breathing 100% oxygen; size of arteriovenous shunt in supine position; chest radiograph; and intensity of contrast at CE. RESULTS: PA was performed in 25 HHT patients with positive findings on CE, 15 of whom had PAVM. Embolization therapy was recommended in 12 patients, and 3 patients had small PAVMs not accessible for therapy. In 10 patients, PAVM could not be demonstrated at PA. The sensitivity and specificity calculated for the screening procedures are as follows: 53% and 90%, respectively, for SaO2; 60% and 100%, respectively, for chest radiograph; 73% and 80%, respectively, for PaO2 in room air; 100% and 40%, respectively, for PaO2 breathing 100% oxygen; and 64% and 80%, respectively, for shunt measurement. CONCLUSION: Initial screening with CE followed by measurement of PaO2 while breathing 100% oxygen seemed to be the best screening procedure for identification of patients with PAVM. Screening with chest radiograph and pulse oximetry was shown to be insufficient.

Chest roentgenogram in the evaluation of heart defects in asymptomatic infants and children with a cardiac murmur: reproducibility and accuracy.

OBJECTIVES: To evaluate the reproducibility and the accuracy of pediatric radiologists' assessments of chest radiographs with respect to the presence or absence of heart defects in children with an asymptomatic heart murmur. DESIGN: Ninety-eight children, ages 1 month to 15 years (median, 30.1 months), referred for evaluation of a heart murmur were consecutively included. They all had a standard chest radiograph and a color Doppler echocardiograph (CDE) performed. Six specialists in pediatric radiology evaluated the chest radiographs independently on two occasions 6 months apart. The radiologists were asked to classify each set of films into one of two categories: heart disease or no heart disease. The outcome of the CDE was considered the definite diagnosis. kappa statistics were used to analyze the reproducibility of the radiologic assessments. Sensitivity, specificity, and the predictive value of a positive and a negative test were used for evaluation of the accuracy of the radiologic assessments. RESULTS: Mean intra- and interobserver kappa values were all <0.6, and the majority were <0.4. Mean sensitivity was 0.3 (range: 0.17-0.52), mean predictive value of a positive test was 0.4, implying that 60% of the positive assessments were falsely positive. Mean specificity was 0.86 (range: 0.75-0.93) and the mean predictive value of a negative test was 0.80 implying that 20% of the negative assessments were falsely negative. CONCLUSION: We found a low reproducibility, as well as a low accuracy, of the radiologic assessments of the chest radiographs of children with an asymptomatic heart murmur with respect to the presence or absence of heart disease. A false-positive radiologic assessment of the chest radiograph with respect to heart defects causes unnecessary anxiety and further examinations, whereas a false-negative assessment might result in omission of relevant investigations and proper identification of the heart defect. We cannot recommend the use of chest radiographs in the initial evaluation of the asymptomatic child with a heart murmur. If a heart defect cannot be excluded by clinical examination a CDE must be performed.

Embolotherapy for pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).

PURPOSE: To evaluate the clinical results of embolization of pulmonary arteriovenous malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia (HHT), the Rendu-Osler-Weber syndrome. MATERIAL AND METHODS: Twelve patients in the county of Fyn, Denmark, were treated with transcatheter embolization of 20 PAVMs using 12 detachable silicone balloons and 26 steel coils. RESULTS: All PAVMs were completely occluded and we observed a significant rise in PaO2 after treatment and a significant decrease in right-to-left shunt estimated by contrast echocardiography. All patients experienced an improved functional level. One patient experienced severe pleurisy and another a rise in temperature following treatment, but otherwise no symptomatic complications were observed. CONCLUSION: Embolotherapy is a definitive treatment for PAVMs: it is very effective with a high success rate and few complications. Patients with HHT are at risk of PAVM and should be screened and treated for PAVMs when these reach a size that is associated with complications. In the detection of PAVMs, contrast echocardiography is a very sensitive method, and follow-up of these patients can be done with contrast echocardiography.

[Percutaneous transluminal embolization of pulmonary arteriovenous malformations]. / Perkutan transluminal embolisering af pulmonale arteriovenøse misdannelser.

A series of nine patients with pulmonary arteriovenous malformations (PAVM) treated with embolotherapy at Odense University Hospital is presented. In all patients the arterial oxygen tension increased after embolisation. PAVM causes right-to-left shunting, which may result in severe hypoxaemia, and, due to lack of the normal filter function of the lung, paradoxical embolism. Women are particularly at risk during pregnancy. Among patients with Hereditary Haemorrhagic Telangiectasia 15-33% also have PAVM. Embolotherapy is a safe and efficacious treatment for occlusion of PAVM. Since serious complications to the disease can be prevented, all HHT patients should be offered screening for PAVM, and treated if required.

Reduced forced expiratory flow in schoolchildren with respiratory symptoms: the Odense Schoolchild Study.

In the present population-based study, spirometric lung function was assessed in symptomatic schoolchildren with and without asthma as compared to an asymptomatic reference group. The primary aim was to investigate if impaired lung function could be demonstrated in symptomatic schoolchildren, even in the absence of diagnosed asthma. Spirometry [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), 50% of forced expiratory flow (FEF 50%) and 75% of forced expiratory flow (FEF 75%)] and anthropometric measures (standing height, weight, skin fold thickness, and length and circumference of the upper arm) were obtained from 1369 8-10-year-old children (81.5% of the eligible population) during the school year 1985-86. In 1321 of those subjects (96.5% of those examined), a self-administered questionnaire was completed. Thirty-five children belonging to ethnic minorities were excluded, thus 1286 subjects were included for further analysis. Point prevalences concerning asthma and respiratory symptoms (wheeze, cough and shortness of breath) were obtained. Thirty-seven children reported asthma and one or more asthma-like symptoms (symptomatic asthmatics), whereas 40 children denied having asthma, although claiming one or more asthma-like symptoms (symptomatic non-asthmatics). In both symptomatic groups, FEF 50% and FEF 75% were reduced relative to the reference group, the deficit being larger in the symptomatic asthmatics. FEF 75% was found to be more reduced than FEF 50%. FEV1 and FVC did not differ significantly between groups. It is concluded that only half of the schoolchildren with respiratory symptoms usually associated with the presence of asthma actually reported having this disease. These results demonstrate the presence of reduced lung function in symptomatic, reportedly non-asthmatic, children, suggesting clinically important underdiagnosis of asthma. More severe impairment of lung function was found in known asthmatics, also implying some degree of undertreatment.

High prevalence of interatrial communications during the first three months of life.

The objective of this study was to analyze retrospectively the results of color Doppler echocardiographic (CDE) investigations performed for the first time on a child under circumstances where there was unrestricted access to CDE. The records were obtained from a tertiary referral center at a university hospital serving a population of about one million. The patients were children (n = 284) ages 0 days to 15 years 9 months referred for CDE over a 1-year period. Heart abnormalities were found in 119 children (42%). Among the children <3 months old, a heart abnormality was detected by CDE in 71%. The most prevalent diagnosis was atrial septal defect, particularly during the first 3 months of life, where the intraatrial communications accounted for 78% of the heart abnormalities. It is concluded that there is high prevalence of atrial communications during the first 3 months of life. The spectrum of diagnoses among newborns differs from the previously reported frequencies of congenital heart diseases. Better equipment (CDE) seems to diagnose abnormalities that might not be diagnosed otherwise.

[Discrepancies between diagnosed asthma, asthma-like symptoms and a test for abnormal lung function]. / Manglende overensstemmelse mellem diagnosticeret asthma, asthmalignende symptomer og test for abnorm luftvejsfunktion.

For the diagnosis of asthma, it is neither clear to which degree various tests and symptoms identify the same subjects nor how these characteristics are best combined. We assessed the interrelationship between physician-diagnosed asthma, asthma-like symptoms and abnormal airway function in a population based sample of 495 12-15 year old schoolchildren. Participants filled in a questionnaire and underwent baseline spirometry (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. Most symptomatic subjects with any test positive were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). Although interest agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, between PEF and EXE and between FEV1% and PD15. However, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology, and the combined use of the two tests may be helpful as an epidemiological screening tool for asthma.

What are the clinical benefits of correcting the catabolic state in haemodialysis patients?

In a double-blind, placebo-controlled trial of recombinant human growth hormone (rhGH) comprising 20 chronic enfeebled haemodialysed patients, the clinical benefit of daily growth hormone treatment for six months was evaluated. Nine patients (five male, four female) were treated with rhGH 4 i.u./m2/day and eleven with placebo (seven male, four female). Their mean age was 46.5 years (range 18-68). No difference in mean age was found between the groups. A significant increase in insulin-like growth factor I (IGF-I) was observed in the rhGH-treated group (200 to 527ng/ml, p = 0.01), while a decrease was noticed in the placebo group (285 to 219ng/ml, p = 0.02). S-GH did not change significantly in either group, and there were no differences between the two groups in terms of weight, haemoglobin, s-albumin, -urea or -creatinine, which all remained unchanged during the trial. Patients' lean body mass, as measured by DXA-scanning, increased significantly in the rhGH-treated group (43.4 to 46.7kg, p = 0.004), while no change was observed in the placebo group (44.9 to 45.2kg, p = 0.76). The changes in lean body mass between the two groups were significant, p = 0.001. Left ventricular muscle mass increased significantly (227 to 286g, p = 0.03) in the rhGH-treated group, but not in the placebo group (292 to 253g, p = 0.3). The changes in left ventricular muscle mass between the two groups were significant (p = 0.02). The maximal working capacity decreased slightly and insignificantly in both groups, when measured by bicycle ergometry. Isometric muscle contraction force and endurance did not change significantly in either group. Patients' opinion about the influence of the treatment on their general well-being and working capacity, evaluated blindly on a subjective scale, improved significantly in the rhGH-treated group (9.7 to 12.6, p = 0.02), while no change was experienced in the placebo group (9.9 to 10.7, p = 0.2). No difference was however demonstrable between the two groups (p = 0.4). Thus we conclude that adult patients in long-term haemodialysis treated with rhGH experienced an increase in their lean body mass and left ventricular muscle mass. This increase in muscle mass did not, however, improve muscle contraction force or endurance when measured objectively. The rhGH-treated patients nevertheless had a subjective feeling of a slight improvement in their general wellbeing.

Interrelationships between diagnosed asthma, asthma-like symptoms, and abnormal airway behaviour in adolescence: the Odense Schoolchild Study.

BACKGROUND: The diagnosis of asthma is based on several characteristics including symptoms and suitable tests of airway lability. However, it is neither clear to what degree various tests and symptoms identify the same subjects, nor how these characteristics are best combined to diagnose asthma. The interrelationships between physician-diagnosed asthma, asthma-like symptoms, and abnormal airway function, as defined by four commonly used tests, have therefore been assessed. METHODS: A population based sample of 495 Danish schoolchildren aged 12-15 years, comprising 292 randomly selected subjects and 203 subjects considered at risk of having or developing asthma, was examined. Symptoms and background information were recorded by questionnaire. The test panel consisted of baseline forced expiratory volume in one second (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. RESULTS: The sensitivity for diagnosed asthma was highest for PD15 followed by PEF monitoring, whereas specificity for asthma or asthma-like symptoms was marginally higher with the other two tests. Most symptomatic subjects with any positive test were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). PEF variability was more susceptible to treatment with inhaled steroids than the PD15 index. Although inter-test agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, PEF and EXE, and FEV1% and PD15. CONCLUSIONS: The agreement between the four tests was weak. In particular, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology. The combined use of methacholine provocation testing and PEF monitoring may be helpful as an epidemiological screening tool for asthma.

Diagnostic value of chest radiography and electrocardiography in the evaluation of asymptomatic children with a cardiac murmur.

We investigated the diagnostic value of the chest radiograph and ECG in the evaluation of whether asymptomatic children with a cardiac murmur had a heart disease as defined by echocardiography. One hundred children aged 1 month to 15 years (median 30.1 months) were included. After physical examination, a tentative diagnosis was made: 53 children had no heart disease, 24 had a probable heart disease and 23 children were thought to have heart disease on the basis of clinical assessment alone. After information from chest radiography and electrocardiography was obtained, the diagnoses were re-evaluated. This resulted in a change of the tentative diagnosis in three children. However, the diagnosis in relation to the definite diagnosis by colour Doppler echocardiography was not changed to the correct diagnosis in any of these cases. In 24 cases, radiography suggested the presence of heart disease; however, only 10 of these had heart abnormalities on the colour Doppler echocardiogram (CDE). Three children had an abnormal ECG; all of these had abnormalities on the CDE, but they were already diagnosed as having heart disease by physical examination. We conclude that chest radiography and electrocardiography is of no help in the discrimination between heart disease and no heart disease in asymptomatic children referred for a cardiac murmur.

[Pediatric evaluation of children with heart murmurs]. / Paediatrisk vurdering af børn med hjertemislyd.

In order to analyse the non-specialized paediatrician's ability to evaluate children with a heart murmur and the consequences of this evaluation for the need of further investigations, we made a prospective and consecutive study concerning 100 children who were referred for initial evaluation of a heart murmur. Based on the clinical evaluation, the children were assigned to one of the three categories of "no heart disease" "heart disease" or "definite heart disease". Within two months each child underwent a complete colour Doppler echocardiographic study. Except for one child with an insignificant peripheral pulmonary artery stenosis, 53% of the children were correctly diagnosed as having no heart disease. We conclude that clinical evaluation without laboratory tests performed by paediatricians without any special training in cardiology could correctly acquit half of the children of heart disease, with no need for further investigation.

Kawasaki disease associated with parvovirus B19 infection.

UNLABELLED: In a 9-week-old boy with Kawasaki disease an active parvovirus B19 infection was diagnosed serologically. CONCLUSION: This case supports the hypothesis of an aetiological relationship between parvovirus B19 infection and Kawasaki disease.

Initial evaluation of children with heart murmurs by the non-specialized paediatrician.

UNLABELLED: To analyse the ability of the non-specialized paediatrician to evaluate children with a heart murmur and the consequences of this evaluation for the need of further investigations, we undertook a prospective and consecutive study of 100 children, referred for initial evaluation of a heart murmur. Except for 1 child with a slight peripheral pulmonary artery stenosis, 53% of the children were correctly diagnosed as having no heart disease. In a project design where 47% of the children were referred for an echocardiographic study, no clinically significant heart disease was missed. CONCLUSION: Clinical evaluation without laboratory tests performed by paediatricians without any special training in cardiology could correctly acquit 50% of the children of heart disease, with no need for further investigation.

Oximetry catheters in diagnostic heart catheterization in children.

The aim of this study was to assess the performance of pediatric-size oximetry catheters in diagnostic heart catheterization. Measurements of pressures and oxygen saturations were obtained with oximetry catheters as well as with standard methods during routine heart catheterizations in 10 infants and children with congenital heart defects. Maneuverability of the oximetry catheters was comparable to that of standard Swan-Ganz catheters. Pressure tracings were damped, but mean pressures were undistorted. Oxygen saturation measurements exhibited bias and scatter. It is concluded that no advantage is obtained by the use of oximetry catheters in diagnostic heart catheterization in children and infants.