Alexander S. Nadas

Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study.

Among 3559 newborn infants with birth weight less than 1750 gm, 421 developing a hemodynamically significant patent ductus arteriosus were entered into a randomized trial to evaluate the role of indomethacin in the management of PDA. Indomethacin given concurrently with usual medical therapy at the time of diagnosis resulted in ductal closure in 79%, versus 35% with placebo (P less than 0.001). Indomethacin as backup to usual medical treatment resulted in similar closure rates. To assess overall effects through hospital discharge, three management strategies were compared. Although mortality did not differ significantly, infants given indomethacin only if usual therapy failed (strategy 2) had a lower incidence of bleeding than those to whom indomethacin was given with initial medical therapy (strategy 1) and lower rates of pneumothorax and retrolental fibroplasia than those to whom no indomethacin was administered, with surgery the only backup to medical therapy (strategy 3). Thus the administration of indomethacin only when medical treatment fails appears to be the preferable approach for the management of symptomatic PDA in premature infants.

Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease.

SUMMARY Fifty patients with congenital heart disease, ages 2 days-30 years (median 12 months) at cardiac surgery, underwent lung biopsy to assess pulmonary vascular disease (PVD). Twenty-six had ventricular septal defects (VSD), 17 d-transposition of the great arteries (D-TGA), and seven, defects of the atrioventricular canal (AVC). Quantitative morphologic data was correlated with hemodynamic data. Three new grades of PVD were observed. Abnormal extension of muscle into peripheral arteries (grade A) was found in all patients; all had increased pulmonary blood flow. In addition, 38 of 50 patients had an increase in percentage arterial wall thickness (grade B); this correlated with elevation in pulmonary artery (PA) pressure (r = 0.59). Another 10 of 50 patients had, in addition to A and B, a reduction in the number of small arteries (grade C); nine of 10 were patients with elevated PA resistance > 3.5 u/m2 (P < 0.005). All three patients with Heath-Edwards changes of grade III or worse also had grade C. Reduction in peripheral arterial number probably precedes obliterative PVD and may identify those patients in whom, despite corrective surgery, PVD will progress.

Cardiac tumors in infancy

Abstract Tumors of the heart in infants are very rare. The neoplasm commonest in adults, intracavitary myxoma, practically never occurs in infancy. Intracavitary fibromas causing obstructive symptons in the left and, rarely, in the right ventricle are commoner in infancy than in older age groups. Rhabdomyomas are the commonest lesions and, when associated with tuberous sclerosis, are relatively easy to recognize on the basis of central nervous system symptoms, their association with kidney and skin tumors and predominance of cardiac arrhythmias. Malignant tumors are rare and untreatable. Metastatic tumors may be hard to recognize since the underlying neoplastic disease usually dominates the clinical findings.

A forty-year review of bacterial endocarditis in infancy and childhood.

A retrospective review of 149 episodes of bacterial endocarditis (BE) in 141 patients under 25 years of age, at The Childrens Hospital Medical Center from 1933 through June of 1972, demonstrates increasing survival and a distinct change in the frequency of underlying congenital heart disease and rheumatic heart disease (RHD). Certain forms of congenital heart disease such as tetralogy of Fallot, small ventricular septal defect, and aortic stenosis are at particular risk for BE. Following BE, patients with ventricular septal defect and tetralogy of Fallot have less morbidity and higher survival rates than children with aortic outflow lesions. over the entire time period, alpha Streptococcus is the most common pathogen and Staphylococcus aureus, second most frequent organism. Surgical correction in patients with congenital heart disease may offer the best form of prevention.

Fixed subaortic stenosis in the young: Medical and surgical course in 83 patients

Eighty-three patients aged 11 months to 25 years were followed up a median of 6.1 years (range 8 days to 24 years) after diagnosis of fixed subaortic stenosis (SAS). Fourteen (17%) had significant noncardiac defects and 47 (57%) had additional cardiac malformations. The left ventricular (LV) outflow gradient increased in 25 of 26 patients catheterized more than once before surgery. Of 15 patients less than 12 years old with gradients less than or equal to 40 mm Hg, 10 ultimately underwent operation after developing severe obstruction; another has progressed to a gradient of 45 mm Hg at 6 years of age. Before surgery (at a median age of 12 years), 55% had aortic regurgitation (AR), which was usually mild. Infective endocarditis occurred in 12% of the group, with a frequency of 14.3 cases per 1,000 patient-years. Seventy-four patients were operated on, with 6 early (8%) and 7 late (9%) deaths. Twelve underwent reoperation to relieve residual obstruction. Surgery reduced gradients in patients with discrete SAS from 83 +/- 33 to 29 +/- 30 mm Hg, but in 6 patients with tunnel SAS the reduction was less satisfactory. AR was absent or mild in most patients postoperatively. When the gradient was reduced to less than 80 mm Hg, infective endocarditis did not occur unless there were other residual lesions. These data suggest that it is reasonable to resect discrete SAS in children less than 10 to 12 years old with LV outflow gradients greater than or equal to 30 mm Hg.

Sepsis and congenital asplenia

Fifty-nine children with congenital asplenia were reviewed for episodes of severe infection. Seven children had isolated asplenia and 52 had asplenia associated with complex congenital heart disease (asplenia syndrome). A control group of eusplenic children with comparable cardiac lesions were assembled and used for comparative statistical analysis. There were 16 instances of documented sepsis among 59 children (27%). In those less than six months of age, the invading organism was usually gram-negative (Escherichia coli or Klebsiella). In children six months of age or older, the infecting organism was usually a pneumococcus or H. influenzae. When those with asplenia syndrome were compared to the control population, the former group had a significantly greater incidence of sepsis. Children with asplenia syndrome who survived the first month of life were at greater risk of dying from sepsis than from their heart disease. It is recommended that prophylactic antibiotics be administered to children with congenital absence of the spleen, commencing at three months of age, to be continued indefinitely.

Clinical profile of patients with congenital corrected transposition of the great arteries. A study of 60 cases.

Abstract Of 60 patients with congenital corrected transposition of the great arteries, 44 (73 per cent) are still alive. The oldest has lived for 41 years and five months, and seven (16 per cent) are over 20 years of age. Twenty-five patients (42 per cent) had a single ventricle, 31 an associated ventricular septal defect, and four an intact ventricular septum. Twenty-seven (45 per cent) had pulmonary stenosis and 23 per cent left-atrioventricular-valve regurgitation. Associated lesions included subaortic stenosis (four) and left-atrioventricular-valve atresia or stenosis (six). The usual ausculatory, roentgenographic and electrocardiographic criteria were found to be inaccurate. Short of autopsy or surgery, catheterization offers the only reliable evidence for the diagnosis. Surgical procedures included Brock valvulotomies, systemic-pulmonary-artery anastomoses, atrial-septal-defect creations, pulmonary-artery bandings and pacemaker insertions. Forty-seven per cent of the original 60 patients are reasona...

Ebstein's anomaly: Clinical profile and natural history

Abstract The clinical features, cardiac catheterization data and natural history of 55 patients with Ebsteins anomaly are presented; 18 had a significant associated cardiac anomaly. The clinical features are usually clear-cut. Cardiac catheterization and angiography demonstrate downward displacement of the tricuspid valve, a large right atrium, no important elevation of the right ventricular pressures, decreased pulmonary blood flow and right to left shunt through the foramen ovale. Right ventricular outflow obstruction may be masked by the low level of pulmonary blood flow and resistance. Intracardiac electrocardiogram is usually diagnostic. The prognosis in these children is relatively poor in the presence of (1) complicating cardiac lesions, (2) more marked cyanosis and (3), to a lesser extent, extreme cardiomegaly. The appearance of congestive heart failure foretells early death ( In neonates presenting with Ebsteins anomaly the incidence of important associated cardiac anomalies is higher, and the clinical picture more variable because of the physiologic adjustments of birth. Cyanosis may be severe only to improve later. The electrocardiogram may show atypical features and exhibit the classic pattern within weeks. Radiographic cardiomegaly may be dramatically out of proportion to the apparent well-being of the infant. Surprisingly gross cardiomegaly is compatible with survival.

Total Anomalous Pulmonary Venous Connection Clinical and Physiologic Observations of 75 Pediatric Patients

Experience with 75 cases of proven total anomalous pulmonary venous connection without other significant cardiac malformations treated at the Childrens Hospital Medical Center in Boston from January 1950 to June 1968 forms the basis of this report. Clinical observations of patients with this defect presenting in infancy are reviewed in depth, and the few patients presenting after 1 year of age are included to give a spectrum of this disease in the pediatric age group.Chest x-rays and complete electrocardiograms were available in each case. Sixty-one patients had partial or complete cardiac catheterizations. The anatomic and physiologic data from these studies are presented, and the results of medical management are evaluated.On the basis of the physiologic data, an approach to management is proposed which includes early operative intervention in those patients with pulmonary vascular obstruction. If pulmonary hypertension is present without vascular obstruction, medical management may be tried. If pulmonary hypertension is not present and particularly if there is a significant gradient across the right ventricular outflow tract, medical management appears to be the treatment of choice until operative intervention can be undertaken with less operative mortality.

Ventricular Septal Defect with Aortic Regurgitation Medical and Pathologic Aspects

Thirty-four patients with ventricular septal defect and aortic regurgitation, representing less than 5 per cent of our patients with ventricular septal defect, are discussed.A loud, systolic murmur, characteristic of ventricular septal defect, is noted during infancy, whereas evidences of aortic regurgitation (protodiastolic murmur and wide pulse pressure) does not usually appear until sometime between 2 and 10 years of age.Clinical and catheterization data indicate that the principal hemodynamic load is aorticregurgitation, whereas the ventricular septal defect does not usually result in a large pulmonary blood flow or high pulmonary arterial pressure. In about 50 per cent of the patients, a significant pressure gradient across the right ventricular outflow tract exists.Detailed pathologic studies indicate that the ventricular septal defects are high and anterior and encroach to a greater or lesser degree on the membranous bulbar septum. The right coronary cusp is the one most severely involved, and, by its prolapse, causes aortic regurgitation; the noncoronary cusp is always less severely affected. The anatomic basis of the pressure gradient observed across the right ventricular outflow tract is not always clear.