Design and implementation of the North American Pediatric Cardiomyopathy Registry.

The Pediatric Cardiomyopathy Registry (PCMR) was established to describe the epidemiologic features and clinical course of selected cardiomyopathies in patients aged 18 years or younger and to promote the development of etiology-specific treatments. Sixty-one private and institutional pediatric cardiomyopathy practices in the United States and Canada were recruited to participate in the PCMR. The registry consists of a prospective, population-based cohort of patients in 2 regions (New England and the Central Southwestern United States) and a retrospective cohort of patients diagnosed between 1991 and 1996. Annual follow-up data are collected on all patients. As of June 1999, the PCMR consisted of 337 prospectively identified and 990 retrospectively identified patients. The PCMR has demonstrated the feasibility of establishing a large database of sociodemographic and clinical information on children with pediatric cardiomyopathy. Through this cooperative effort, the PCMR will obtain precise estimates of the incidence of pediatric cardiomyopathy and a better understanding of the natural history of this disease.

Findings on endomyocardial biopsy in infants and children with dilated cardiomyopathy.

Fifteen infants and children with dilated cardiomyopathy underwent transvascular endomyocardial biopsy. The light and electron microscopic findings were reviewed to evaluate the presence of lymphocytes as an indicator of active myocarditis. Both ventricles were biopsied in 13 patients, and the right ventricle only was biopsied in 2. None of the endomyocardial specimens obtained by biopsy revealed an inflammatory process. Interstitial fibrosis, myofiber hypertrophy, degeneration and necrosis were found. Ultrastructural abnormalities of the mitochondria, T tubules or Z bands were noted in approximately one-third of patients. Persistent, active myocarditis is an uncommon cause of dilated cardiomyopathy in children. Immunosuppressive therapy, which may be harmful, should be considered only after myocardial inflammation has been documented by endomyocardial biopsy.

Transaortic occlusion of collateral arteries to the lung by detachable valved balloons in a patient with tetralogy of Fallot.

A 5-year-old boy with tetralogy of Fallot, near-atresia of the right ventricular outflow tract and large collateral arteries to the lungs underwent an infundibulectomy without closure of the ventricular septal defect. Further surgery required preliminary reduction of the collateral circulation. The collateral arteries were successfully occluded by metrizimide-filled balloons. There was no change in arterial oxygen saturation, nor were there any complications. This new technique has significant advantages over existing alternatives.

Restrictive cardiomyopathy with pseudotumor formation of the left ventricle.

A 4-year-old girl had the insidious onset of congestive heart failure without apparent cause. Evaluation by echocardiography, thallous chloride TI 201 scintigraphy, and angiography suggested the presence of either a neoplasm or restrictive cardiomyopathy with a localized mass effect on the left ventricle. Pathological specimens obtained by transvascular endomyocardial biopsy and at surgery defined the pathology to be restrictive cardiomyopathy. Analysis of myocardium by electron microscopy demonstrated a previously undescribed abnormality of the contractile elements involving the myofilaments and Z bands, with generalized secondary glycogen deposition.

The fontan procedure for tricuspid atresia.

A modified Fontan operation was performed on nine patients, ages 8--24 years (mean 14 years), with tricuspid atresia. The right atrium and right ventricle were connected with a valved conduit in five patients and directly in four. A porcine inferior vena caval valve was used in two patients. Prior operations had been performed in eight patients. There were no surgical deaths. Complications included pleural effusions, low-output syndrome, renal failure and atrioventricular block. There were two late deaths, only one of which was of cardiac origin. One patients required reoperation because of residual atrial septal defect at 1 month and again at 56 months for conduit stenosis. One patient required a pacemaker. Follow-up extends 6--65 months (mean 34 months). Survivors are clinically well and active, although four are taking medications. Postoperative cardiac catheterizations were done in six patients. Right atrial pressures were elevated in each, with no gradients across the conduit or pulmonary valve except in the one patient with conduit obstruction. Three patients had small residual ventricular septal defects and one a residual Blalock anastomosis. The Fontan procedure is an effective operation for tricuspid atresia. It may be further modified by establishing direct continuity between right atrium and right ventricle without a valve conduit in patients with a functioning pulmonary valve. The long-term ability of the right atrium to maintain adequate pulmonary flow and the effects of chronically elevated right atrial pressure on hepatic function and the cardiac conduction system must still be examined.

An X-linked recessive cardiomyopathy with abnormal mitochondria.

A transvascular endomyocardial biopsy from an infant with cardiomyopathy and chronic congestive heart failure showed abnormal mitochondria when examined by electron microscopy. At necropsy, similar abnormal mitochondria were seen in skeletal muscles, liver, and kidney. The patient's family pedigree revealed several male babies who had cardiac disease and died in infancy. Myocardium obtained at necropsy from three cousins contained mitochondria with abnormalities similar to those from the proband. An X-linked recessive cardiomyopathy seems likely in this family.

Endocardial fibroelastosis found on transvascular endomyocardial biospsy in children.

Left ventricular endocardium obtained by transvascular endomyocardial biopsy from nine infants and children with various congestive cardiomyopathies showed thickening in five, with hyperplasia of endocardial cells and increase in elastic and collagen fibers (endocardial fibroelastosis). Based on the morphologic findings, we suggest a chronologic sequence of hyperplasia of smooth muscle (SM) cells followed by transformation and translocation. The sequence appears to be (1) proliferation of dark SM cells with many surface vesicles, many myofilaments, and fusiform densities; (2) possible proliferation of light SM cells containing fewer surface vesicles and fewer myofilaments than the dark SM cells; (3) transformation of SM cells to leiomyoid cells that resemble both SM cells and fibroblasts; and (4) transformation to typical fibroblasts. The cells producing the increased elastin and collagen are believed to be the SM cells and the leiomyoid cells.

Transvascular endomyocardial biopsy in infants and small children. Myocardial findings in 10 cases of cardiomyopathy.

Transvascular endomyocardial biopsy specimens from nine children with congestive cardiomyopathy and one with hypertrophic cardiomyopathy were studied by light microscopy using sections 1 mu thick cut from Epon embedded tissue and by electron microscopy. There was a disparity between the severity of the physiologic impairment and the morphologic abnormalities. Interstitial fibrosis was present only in the one case in which significant viral antibody titers were obtained. The sizes of the cardiac muscle cells varied abnormally in all specimens. Cardiac muscle cells in two patients contained abnormal mitochondria, and a leptomeric fibril was found in one patient. Virologic cultures of the tissues were negative and no viral particles were identified by electron microscopy. An attempt was made to correlate the clinical and pathologic findings.

Administration of prostaglandin E1 in neonates with critical congenital cardiac defects.

Prostaglandin E1 was administered to 12 neonates and young infants in whom pulmonary or systemic blood flow was entirely or significantly dependent upon persistent patency of the ductus arteriosus. Nine neonates responded favorably to PGE1 infusion; their mean age was 2.8 days. Three infants who failed to respond were 10 days, 14 days, and 9 weeks of age, respectively. Six neonates with right ventricular outflow obstruction had a mean increase in arterial PO2 of 136% following administration of PGE1. In three patients in whom systemic flow was ductus dependent, PGE1 infusion was followed by improvement in arterial blood pressure, peripheral perfusion, and urine output. Complications included pyrexia, vasodilatation, and myoclonic jerks (or focal seizures). Three side effects were easily reversible by decreasing the infusion rate or altering the site of administration. PGE1 is a highly effective agent in stabilizing critically ill neonates with ductus dependent congenital cardiac lesions.

Transvascular endomyocardial biopsy in infants and small children: description of a new technique.

A miniaturized technique for transcatheter endomyocardial biopsy has been developed in the belief that myocardial biopsy performed in infancy, when the disease process in cardiomyopathy may be most active, should yield important etiologic and nosologic information. To obtain six biopsy specimens, three from each ventricle, adds about 1 hour to a diagnostic right and left heart catheterization. A no. 4 or 5 French forceps with a modified soft shaft is guided to the site in theapical septum of the right and left ventricles through a previously molded to measure guide tube of ultrathin radiopaque Teflon. With biplane fluoroscopy the guide tube of ultrathin radiopaque Telflon. With biplane fluorsocopy the guide tube is introduced as a sheath over a matching catheter and the catheter is removed. Contrast medium in injected to verify position, the forceps is introduced and the biopsy specimen is taken. If the forceps is sharp and pressure on the endocardium in light, evidence of biopsy is not discrenible on examination of the heart 1 week later. The method was developed in small dogs and proved safe and effective in rabbits weighing 3 kg. Biopsy has been performed safely in children aged 4 1/2 months to 5 1/2 years and weighing 4.5 to to 19.6 kg.

De subitaneis mortibus. XXX. Observations on the pathophysiology of the long QT syndromes with special reference to the neuropathology of the heart.

Eight patients (different families) with syncopal attacks and a long QT interval in the ECG died suddenly. Five heard normally and three were born deaf. At postmortem examination of all eight hearts the single consistent abnormality was focal neuritis and neural degeneration within the sinus node, A-V node, His bundle and ventricular myocardium. Although the etiology of this intracardiac neural disease is uncertain, a chronic viral infection or some noninfectious degenerative process are among the plausible causes discussed. If intracardiac neuritis and neural degeneration prove to be a prevalent finding among other victims dying from the long QT syndromes, further consideration should be given to whether there is any genuine hereditary component in the pathogenesis. Because of the asymmetrical and focal distribution of the cardioneural lesions, the response to present forms of medical or surgical treatment of the lung QT syndromes may vary from benefit to harm. Until more is known of the true etiology of the neural disease, treatment will probably remain empirical in nature and should be conducted with cautious clinical observation.

Prolonged prostaglandin E1 infusion in an infant with cyanotic congenital heart disease.

A small-for-gestational-age premature infant with severe tetralogy of Fallot was treated with prostaglandin E1 to dialate the ductus arteriosus and increase pulmonary blood flow. The infusion was continued for 29 days without complication at which time surgery was performed.

Long-term results of the Mustard procedure.

Over a 10-year period, 123 patients with transposition of the great vessels underwent the Mustard procedure. The hospital mortality for the series was 10.6%. There were seven late deaths, five of which were presumable due to arrhythmia. Sinus rhythm was noted postoperatively in 53% of the patients. Almost all the survivors had achieved catch-up growth when evaluated 6 months to 10 years later. A growth spurt was more consistently seen in the patients who were operated on under 2 years of age. Physical endurance and school performance were on a par with their normal peers or better in about half of the survivors. Severe neurologic problems were present in five patients. Postoperative catheterizations in 42 patients showed a rather high incidence of residual interatrial shunts, mild left ventricular outflow obstruction, and mild superior vena caval obstruction. Pulmonary venous obstruction and serious tricuspid regurgitation were not encountered.

An assessment of Mustard's operation as a palliative procedure for transposition of the great vessels.

Ten patients in whom palliative Mustard operations have been performed for transposition of the great vessels with ventricular septal defect and elevated pulmonary vascular resistance are reported. There has been early or late mortality in this group of patients, and postoperative morbidity has been minimal. Five of them have been recatheterized, and the results indicate substantial improvement in postoperative arterial oxygen saturation with change in pulmonary vascular resistance. The operation is reserved for those patients in whom peripheral desaturation is the major cause of symptomatology. Clinical improvement has been gratifying, and the continued use of the operation in selected patients seen indicated.