Detection of phosphomonoester signals in proton-decoupled 31P NMR spectra of the myocardium of patients with myocardial hypertrophy.

Proton-decoupled 31P NMR spectroscopy at 1.5 T of the anterior left ventricular myocardium was used to monitor myocardial phosphate metabolism in asymptomatic patients with hypertrophic cardiomyopathy (HCM, n = 14) and aortic stenosis (AS, n = 12). In addition to the well-known phosphorus signals a phosphomonoester (PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This signal was not observed in the spectra of normal controls (n = 11). We suggest that in spectra of patients with myocardial hypertrophy the presence of a PME signal reflects alterations in myocardial glucose metabolism.

Effects of cardiopulmonary bypass and inhaled nitric oxide on platelets in children with congenital heart defects.

UNLABELLED: Nitric oxide (NO) reduces platelet aggregation in vitro. However, repeated measurements of platelet aggregation in infants and small children are impossible due to the large blood samples required. Instead, the expression of different platelet receptors mediating platelet adhesion (CD 36 and CD 42b), activation (CD 42b and CD 61) and aggregation (CD 41a) was measured repeatedly by flow cytometry. First, the expression of platelet receptors was quantified in platelet suspensions of 20 healthy volunteers after incubation with different concentrations of NO (0, 25, 100 and 640 ppm) and compared to changes in platelet aggregation and intrathrombocytic cGMP levels. It was then studied in 21 infants and children before, during and up to 3 days after cardiopulmonary bypass surgery. Seven of these patients required NO inhalation postoperatively. The in vitro experiments showed a reduced expression of the CD 41a, CD 42b and CD 61 receptors with increasing doses of NO, predominantly affecting the CD 41a receptor (-11% at 100 ppm and -20% at 640 ppm). This significant effect is in keeping with the observed NO-induced inhibition of platelet aggregation (-44% at 100 ppm) and the rise in platelet cGMP levels (+69% at 100 ppm). In patients without inhaled NO, the expression of CD 41a was slightly attenuated during cardiopulmonary bypass surgery (-15%) but increased significantly afterwards (2 h: +31%, 1st day: +129%, 2nd day: +120%, 3rd day: +111%). Comparable results were obtained regarding the other adhesion molecules CD 36, CD 42b and CD 61. In patients with inhaled NO the same pattern was observed and analysis of variance did not reveal any significant difference between both groups of patients. CONCLUSIONS: NO (> or = 100 ppm) decreases the expression of different platelet adhesion molecules and platelet aggregation, presumably via an increase in intracellular cGMP. However, due to the low dose range used in the clinical setting (1-40 ppm) this is clinically not relevant. Immediately after cardiopulmonary bypass surgery the expression of these adhesion molecules is reduced, but recovers on the 1st postoperative day.

Proton-decoupled myocardial 31P NMR spectroscopy reveals decreased PCr/Pi in patients with severe hypertrophic cardiomyopathy.

Disturbed myocardial energy metabolism may occur in patients with primary hypertrophic cardiomyopathy (HCM). A noninvasive way to gain insight into cardiac energy metabolism is provided by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectroscopy with proton decoupling was performed in 13 patients aged 13-36 years with HCM on a 1.5 T Magnetom with a double resonant surface coil. A 2D chemical shift imaging (CSI) sequence in combination with slice selective excitation was used to acquire spectra of the anteroseptal region of the left ventricle (volume element: 38 mL). The chemical shifts of the phosphorus metabolites, intracellular pHi, and coupling constants J(alphabeta) and J(gammabeta) were calculated. Peak areas of 2,3-diphosphoglycerate (DPG), Pi, and adenosine triphosphate (ATP) were determined and corrected for blood contamination, saturation, and differences in nuclear Overhauser enhancements (NOE). The maximum thickness of the interventricular septum (IVSmax) was determined from tomographic long-axis images and expressed as number of standard deviations above the mean of the normal population (Z score). The patients were then divided into 2 groups: 6 patients with moderate HCM (HCMm, Z score < or = 5) and 7 patients with severe HCM (HCMs, Z score > 5). No differences between both groups and a control group of healthy volunteers (n = 16) were found with respect to phosphocreatine (PCr)/gamma-ATP ratio, pHi, or the coupling constants. Only the PCr/Pi ratio differed significantly from the control group (HCM(all), alpha < 0.05, HCMs, alpha < 0.02, 2-sided U test). The decrease of the PCr/Pi ratio in patients with HCM is probably caused by ischemically decreased oxygen supply in the severely hypertrophied myocardium.

Increased turnover of serotonin in children with pulmonary hypertension secondary to congenital heart disease.

Serotonin (5HT) is a potent vasoconstrictor of the pulmonary vascular bed and may be involved in the pathophysiology of secondary pulmonary hypertension in children with a left-to-right shunt due to a congenital heart defect. To test this hypothesis we measured the total and free 5HT concentration in blood as well as the urinary excretion of its main metabolite 5-hydroxyindoleacetic acid (HIAA) in children showing a left-to-right shunt with (n = 10) and without (n = 18) pulmonary hypertension. 5HT and HIAA were also measured in children after corrective cardiac surgery using cardiopulmonary bypass (n = 14) and in controls without congenital heart disease (n = 18). The concentrations of total and free 5HT were not significantly different between controls and patients with a left-to-right shunt. After cardiac surgery total 5HT concentration was significantly reduced by about 65% owing to a postoperatively reduced platelet count. In patients with a left-to-right shunt the total 5HT content was similar in the right atrium (204.0 +/- 17.3 ng/ml), pulmonary artery (189.0 +/- 19.1 ng/ml), and aorta (195.0 +/- 19.3 ng/ml), as was the free 5HT concentration. Therefore no net release of 5HT from platelets occurred between these sampling sites. In patients with pulmonary hypertension, the urinary excretion of HIAA was significantly increased when compared with controls and patients without pulmonary hypertension. It is concluded that turbulent blood flow in children with a left-to-right shunt does not lead to a significant release of 5HT from platelets. However, the increased urinary excretion of HIAA in patients with pulmonary hypertension indicates an increased turnover of 5HT, probably due to an increased number of intrapulmonary neuroepithelial cells or a higher metabolic rate of 5HT within those cells.

[Improvement of perioperative hemodynamics and gas exchange by inhalation of nitric oxide in children with congenital cardiopulmonary defects]. / Verbesserung der perioperativen Hämodynamik und des Gasaustausches durch Inhalation mit Stickstoffmonoxid bei Kindern mit angeborenen kardiopulmonalen Fehlbildungen.

OBJECTIVES: In critically ill infants and children before or after surgery for congenital cardiopulmonary disease it was evaluated whether continuous NO inhalation can reduce pulmonary artery pressure (PAP) and improve arterial oxygen saturation (SaO2). METHODS: All patients (n = 24; age 1 day-6.5 years) were intubated and artificially ventilated. They had either secondary pulmonary hypertension (n = 16), acute respiratory distress syndrome (n = 3), or reduced SaO2 (n = 5) due to pulmonary hypoperfusion. NO was introduced into the afferent limb of the ventilator circuit close to the endotracheal tube, while continuously measuring the inspired NO and O2 concentrations. The initially applied concentration of NO was 20 +/- 2.0 ppm. RESULTS: The hemodynamic condition and/or oxygen saturation was significantly improved by NO in 23 patients (95%). Mean PAP declined significantly from 45 +/- 7 to 28 +/- 3.7 mm Hg, while mean systemic arterial pressure remained constant (56 +/- 2.1 vs. 58 +/- 2.5 mm Hg). This was related to a selective reduction in pulmonary vascular resistance by 48 +/- 8.5%. SaO2 increased significantly (p < 0.05) from 83 +/- 2.5% to 93 +/- 1.5% due to a decreased intrapulmonary right-to-left shunt. NO therapy was applied with a median of 6 days (range 1.5-36 days). During NO inhalation methemoglobin concentration was significantly increased (0.77 +/- 0.05% vs. 1.46 +/- 0.15%), but neither was oxygen transport capacity affected, nor was any evidence for accumulation observed. Using a model ventilatory circuit, a nitric dioxide (NO2) formation of 1.14 +/- 0.11% of the applied NO concentration was measured, i.e. approximately 0.5 ppm NO2 at 40 ppm NO. This amount of NO2 in the inspired gas is well below toxicologically relevant concentrations. CONCLUSIONS: Low-dose NO inhalation selectively reduces PAP and improves SaO2 in children with congenital cardiopulmonary disease during perioperative intensive care. It is expected that the overall hemodynamic improvement is related to a reduced afterload of the subpulmonary ventricle without changes in coronary perfusion pressure, as is often observed with other vasodilators applied intravenously. We recommend an upper dose limit of 40 ppm NO for continuous NO inhalation to avoid possible toxicologically relevant NO2 concentrations.

[Abnormal origin of the right coronary artery from the pulmonary artery. A case report]. / Fehlabgang der rechten Koronararterie aus der Arteria pulmonalis. Eine Fallbeschreibung.

An asymptomatic 4-year-old girl with anomalous origin of the right coronary artery from the pulmonary trunk is reported. Echocardiography showed overall dilated coronary arteries with anomalous course of the right coronary artery anterior to the aortic root. During heart catheterization the catheter could be moved from the proximal pulmonary trunk into the aberrant right coronary artery. Because of the coronary-pulmonary steal phenomenon corrective surgery with aortic reimplantation of the right coronary artery is recommended even in asymptomatic patients.

[Anomalous origin of the left coronary artery from the pulmonary artery. Variability of clinical aspects, echocardiography and angiography findings]. / Fehlabgang der linken Koronararterie aus der Pulmonalarterie. Variabilität von Klinik, echokardiographischen und angiographischen Befunden.

OBJECTIVES: Analysis of symptoms, diagnostical difficulties and follow-up in infants and children with anomalous origin of the left coronary artery from the pulmonary artery. METHODS: Retrospective study; 12 children between 3 weeks and 2 years old; time period: 1980-1991. RESULTS: Three infants were detected on routine examination because of a new cardiac murmur, the others presented with signs of cardiac failure. Cross sectional echocardiography and color Doppler flow mapping allowed to verify the suspected diagnosis. However, in one infant a false-negative cross sectional echocardiographic result was obtained. In this case nuclear magnetic resonance imaging was able to delineate the exact anatomy. Mean preoperative left ventricular ejection fraction: 33 +/- 4%; percentage of infants below the age of 6 months: 92%; surgery related mortality: 66%; mean follow-up of the remaining 4 patients being in good clinical condition: 2.9 +/- 1 years. CONCLUSIONS: 1. An anomalous origin of the left coronary artery should be included into the differential diagnosis when a new cardiac murmur is detected. 2. Possibility of false-negative echocardiographic results is emphasized. 3. With early symptoms and highly reduced left ventricular function, the mortality is still high.

Early and late results of the modified Waterston shunt with PTFE grafts for palliation of complex congenital cyanotic heart disease in neonates.

During a 12 year period from 1978 to 1989, 35 infants under 4 weeks of age underwent palliative surgery for complex congenital cyanotic heart disease with a short (1-1.5 cm) PTFE graft between the ascending aorta and the right pulmonary artery (modified Waterston shunt). Twenty-three infants had pulmonary atresia and 14 had severe pulmonary stenosis. Underlying cardiac lesions were tetralogy of Fallot (n = 11), single ventricle (n = 7), transposition complexes (n = 6), and intact ventricular septum and hypoplastic right heart syndrome (n = 13). There were 4 early deaths (10.7%) in the entire series, 2 of which were shunt related. Three of the 4 occurred during our initial experience with this shunt in 1978 and 1979. They led to the modified Waterston shunt being abandoned for 3 years in favor of other shunt procedures. Since 1983 one early death occurred in 28 infants (3.5% mortality) with no death in the latest 26 patients. All patients were followed up between 6 and 108 months. There were 4 late deaths, one of which was shunt related. We observed a significant difference in the shunt patency rate between 4 and 5 mm grafts: palliation was adequate after 2 years in 52% of the patients when a 4 mm graft was used and in 89% of the 5 mm graft group (p less than 0.005). Reshunting was necessary in 7 infants between 5 and 60 months after primary surgery. Recatheterization was performed in 17 infants for suspected shunt failure (n = 6) or diagnostic reasons (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

Endomyocardial biopsy in infants and children: experience in 60 patients.

In 60 children, aged between 1 month and 22 years (median 3.54 years) and with a body weight of 3-67 kg (median 12.6 kg), transvascular endomyocardial biopsy (EMB) was performed from the right (35 children) or left ventricle (30 children). The specimens were investigated by light and electron microscopy. There were three indications for biopsy: (1) poorly functioning, dilated left ventricle (seven patients with endocardial fibroelastosis, 16 with dilated cardiomyopathy, six from healing/healed or chronic myocarditis); (2) unexplained left ventricular hypertrophy (10 with hypertrophic cardiomyopathy, four with secondary hypertrophy, three with storage diseases); (3) to answer certain questions in eight children (four with hypoxic and two with cytoxic myocardial damage). Retrospectively, there were five nonindicated biopsies. There were no serious complications. Biopsies were diagnostic in 11.7% of cases, helpful in 71.7%, and of no help in 16.6%. Thus even in childhood endomyocardial biopsy is a diagnostic tool which can add useful information on the etiology or pathogenesis of an underlying myocardial disease.

[Interventional cardiology in children]. / Interventionskardiologie im Kindesalter.

Interventional heart catheterizations are catheterizations for a therapeutic purpose. The widest spread example is the balloon atrioseptostomy (BAS) according to Rashkind, which is performed in patients with transposition of the great arteries preceding interatrial corrective surgery, in patients with right-sided valve atresias and interatrial obstruction and in patients with complex mitral atresia. In 248 BAS, performed within 20 years we observed 26 (= 10.5%) minor and 3 (= 1.2%) lethal complications. When the BAS is ineffective or the atrial septum very muscular, the Park-blade-septostomy may be performed, provided corrective surgery is out of question. intravasal foreign bodies, e.g. catheter fragments can be extracted without harm and risk by the Dotter retriever. This prevents grave complications. Arteriovenous aneurysms, coronary fistulas or aortopulmonary collaterals can be embolized by steel coils, detachable balloons or Ivalon particles. With increasing frequency patent ducts, seldom also atrial or ventricular septal defects are closed by means of the Rashkind occluder. Balloonvalvuloplasty (BVP) of pulmonary or aortic stenosis became generally accepted. In cooperative studies of the German Society of Pediatric Cardiology in 305 BVP's of pulmonary stenosis 4% complications with one late death have been observed. In aortic stenosis of children early mortality was 1.6%, complication rate 20%, in the critical aortis stenosis of infants early mortality was 19%, complication rate 50%. So BVP of pulmonary and non-critical aortic stenosis may be considered as the treatment of choice, while BVP of critical aortic stenosis and other stenosis of valves or vessels has to be further evaluated.

[Aneurysm of the vein of Galen as a possible cause of congestive heart failure: a report of 5 new cases]. / Aneurysma der Vena Galeni als mögliche Ursache für eine kongestive Herzinsuffizienz: Bericht über 5 neue Fälle.

We report on five newborns with an arterio-venous malformation of the vein of Galen. All newborns were cyanotic and in congestive heart failure without any evidence of congenital heart disease. Congestive heart failure in these cases was mainly due to an almost two-fold increase in cardiac output of approximately 8 l/min/m2 (normal: 4.5 l/min/m2). According to previous reports, mortality is very high in patients with this malformation when becoming symptomatic during infancy, and therapy by surgery or embolization is only successful in 10-30%. While three of our patients died shortly after diagnosis because of untreatable heart failure, the other two were operated on either by subtotal ligation of the draining vein or by ligation of 4 arterial feeders. In the first case secondary thrombosis of the aneurysm occurred and cardiac failure subsided. In the second case a large shunt remained and a balloon-embolization was performed successfully. However, in both patients severe neurologic defects occurred, the severity of which remains to be assessed later since the post-operative observation period is only 2 and 5 months, respectively.

[Secondary diseases of the heart muscle and their differential diagnosis in childhood]. / Sekundäre Herzmuskelerkrankungen und ihre Differentialdiagnose im Kindesalter.

Possible causes of specific cardiac muscle disease, diagnosis, follow-up and the therapeutic management are discussed on the basis of a series of cases. 8 out of 30 patients who showed the clinical picture of dilative cardiomyopathy (DCM) were found to have a specific cardiac muscle disease. 4 patients had DCM following adriamycin therapy. Fibromuscular dysplasia with renal hypertension, thalassaemia major with secondary haemosiderosis, long-overlooked and untreated athyroidism each caused one case of dilative specific cardiac muscle disease. Once DCM was preceded by the Kawasaki syndrome for over 2 years. Amongst 47 patients with hypertrophic cardiomyopathy there were two children who had undergone ACTH treatment, 6 children born of diabetic mothers, 4 cases of Pompe's disease, and one patient with hypothyroidism resulting in reversible hypertrophy of the cardiac muscle. Different neurodegenerative diseases were associated with cardiac muscle disease in 4 cases, partly dictating the clinical course. Extremely rare was the development over 6 years of cardiac hypertrophy following a burns injury.

Repair of symptomatic aortic coarctation in the first three months of life. Early and late results after resection and end-to-end anastomosis and subclavian flap angioplasty.

During a 9 year period between January 1977 and December 1985, 98 consecutive infants under 3 months of age underwent surgical repair of symptomatic aortic coarctation. Resection and end-to-end anastomosis was performed in 73, subclavian flap angioplasty in 14, and other procedures in 11 patients. There were 20 (20.5%) early and 12 (12.5%) late deaths. No early deaths occurred in the isolated coarctation group. Associated complex cardiac malformations and age under 2 weeks at operation influenced significantly early and late outcome but not any particular surgical procedure. The survivors were followed from 6 months to 8 years and 8 months postoperatively. There were 16 (28%) re-coarctations among 56 survivors after end-to-end anastomosis requiring re-operation in 7 (12%) infants and 3 (30%) re-coarctations among 10 survivors after subclavian flap angioplasty requiring re-operation in 1 infant. After end-to-end anastomosis re-coarctation as well as re-operation rate was markedly lower when an interrupted suture line for the entire anastomosis was used as compared to the group with a continuous suture line of the posterior aortic wall (21% vs. 33% re-coarctation rate and 4% vs. 18% re-operation rate respectively). From our results it is concluded that subclavian flap angioplasty for relief of aortic coarctation in early infancy is not superior to resection and end-to-end anastomosis. In the end-to-end anastomosis group an interrupted suture line has a lower re-coarctation as well as re-operation rate as compared to a continuous suture line of the posterior aortic wall.

[Hemodynamics and histology of lung blood vessels in 191 patients with atrioventricular canal]. / Hämodynamik und Histologie der Lungengefässe bei 191 patienten mit atrio-ventrikulärem Kanal.

The correlation between hemodynamic and histological changes of the small lung arteries was examined in 191 patients with atrio-ventricular canal. Lung biopsies were taken during palliative or corrective surgery. The histological findings were classified according to the Heath and Edwards-grading. The haemodynamic data were obtained within 3-4 months before operation (pulmonary/systemic ratios of systolic pressure, flow, and resistance as well as mean pulmonary artery pressure). The results indicated that the term atrioventricular canal must be divided into three different subgroups with regard of the development of HPVD: I. The incomplete atrio-ventricular canal (IAVC) showed a strong correlation between pulmonary hypertension and histological changes. II. The VSD-III (endocushion defect) developes HPVD in the first month of life similar to the complete av-canal. In about all children of this subgroup a serve pulmonary hypertension was found, therefore a correlation to the variety of histological findings could not be established. III. The CAVC was the largest subgroup of our patients. These patients had relatively the highest incidence of high-grade histological alterations. In 87% of the children with CACV we found histologically changes of the structure of the small arteries of the lungs mostly a hypertrophy of the media, but also alterations of the intima as proliferation of fibrosis. 88% of the children within the subgroup CAVC also hat a pulmonary hypertension with a systolic pressure ratio above 0.8.(ABSTRACT TRUNCATED AT 250 WORDS)

[Endomyocardial biopsy in childhood--experiences in 60 pediatric patients]. / Endomyokardbiopsie im Kindesalter--Erfahrungen bei 60 pädiatrischen Patienten.

In 60 pediatric patients, aged from 1 month to 22 years (median 3.54) and a bodyweight of 3 to 67 kg (median 12.6 kg) transvascular endomyocardial biopsy was performed from the right (35 patients) or left ventricle (30 patients). The specimens were investigated by light and electron microscopy. Immune serological investigations were performed in 22 patients, immune histological examinations in eight. There were three indications for biopsy: a. 29 children had a poorly functioning, dilated left ventricle. Of these, seven suffered from endocardial fibroelastosis, 16 from dilated cardiomyopathy, six (plus one control-biopsy) from healing/healed or chronic myocarditis. b. 17 children showed inadequate left ventricular hypertrophy. Of these, ten suffered from HCM, four from secondary hypertrophy, three from storage diseases. c. Various questions were answered in eight children - four with hypoxic, two with cytotoxic myocardial damage. There were five misindications, retrospectively. We observed no serious complications. Evaluation of biopsy revealed diagnostic findings in 11.7%, was helpful in 71.7% and of no help in 16.6%. Hence, even in childhood, endomyocardial biopsy is a diagnostic tool which can contribute useful information on the etiology or pathogenesis of the underlying myocardial disease.

Dilated cardiomyopathy in childhood: problems of diagnosis and long-term follow-up.

Clinical profile and course of 13 infants and children (median age 2 years, range 2 months to 17 years) with dilated cardiomyopathy are presented. Endocardial fibroelastosis and myocarditis were excluded by transvascular endomyocardial biopsy. Elevated cardio-thoracic ratio (mean 0.67), depressed fractional shortening (mean 13%) and cardiac index (mean 2.52 l min-1 m-2) were the indicators of congestive heart failure. During a mean follow-up of 41 months (range 6 to 204 months) five patients died, four remained in a stable condition, four improved. The main complications were rhythm disturbances (23%) and thrombus formation (15%). We could not identify any predictors of survival.

[Hypertrophic cardiomyopathy in childhood: studies of the clinical picture and course]. / Hypertrophe Kardiomyopathie im Kindesalter: Beobachtungen zum klinischen Bild und Verlauf.

30 children with hypertrophic cardiomyopathy and a mean age of 4.9 +/- 4.4 years, 11 infants and 19 children, were followed up for an average of 6.6 +/- 5.6 years. Apart from a systolic murmur in nearly all patients, only a few had symptoms. 7 patients from 5 families had a positive family history. The ECG often showed left ventricular hypertrophy, twice a deep Q wave, and no cases of giant T wave. A subaortic pressure gradient greater than or equal to 40 mm Hg was measured in 6 children, a secondary cardiomyopathy was excluded by biopsy in 8. Associated lesions were coarctation (n = 2) and patent ductus arteriosus (n = 2). 7 children died: 1 infant in congestive heart failure, 3 children suddenly, and 3 postoperatively. The annual mortality rate was 3.5%. Also in childhood, beta-blocker therapy may not prevent sudden cardiac death, nor may operation prevent late complications. In spite of the lack of pressure gradients, the children did not fulfil the criteria of hypertrophic non-obstructive cardiomyopathy.

[Cardiomyopathies in childhood]. / Kardiomyopathien im Kindesalter.

Primary cardiomyopathies are heart muscle diseases of unknown cause. In hypertrophic cardiomyopathy (HCM) a hypertrophy of unknown aetiology results either in asymmetric septal hypertrophy (mostly with obstruction) or in concentric hypertrophy of the left ventricle (mostly without obstruction). This condition is rare in childhood, partly inherited and sometimes observed already in newborns. Sudden cardiac death is a main complication in the second decade. In non-obstructive HCM endomyocardial biopsy is the tool to differentiate secondary forms. Dilated cardiomyopathy is recognized by aetiologically unclear dilatation of left or right or both ventricles. In childhood this condition has to be differentiated from coronary anomalies, endocardial fibroelastosis, and myocarditis. Also rare secondary forms have to be considered because of possible therapeutic consequences. From the very few histologically proven reports a reliable prognosis for this disease in childhood cannot be deduced.