The congenital anomaly in which the left coronary artery arises from the main pulmonary artery is infrequent, but lethal, and since it can be alleviated surgically, its recognition and hemodynamic consequences are important. On the basis of 140 reported cases and our seven cases, it seems to present in one of four ways: (1) in infancy with angina-like symptoms or as cardiomyopathy, and later (2) as mitral insufficiency, (3) continuous murmur, or in adults (4) by sudden death. Visualization of the coronary arteries provides the definitive diagnosis, and the problem is the selection for this procedure. The electrocardiogram, the most helpful laboratory aid, is diagnostic of infarction in 80% of the infant group; in the remainder other forms of cardiomyopathy may be confused. Although blood flows directly into the pulmonary artery in the majority of cases, it flows in the reverse direction in a few and this must be determined preoperatively. Some unanswered questions are the subject of discussion: Why the ma...

Anomalous origin of the left coronary artery from the pulmonary trunk. Its clinical spectrum, pathology, and pathophysiology, based on a review of 140 cases with seven further cases

Objective. Infantile Pompe’s disease is a lethal cardiac and muscular disorder. Current developments toward enzyme replacement therapy are promising. The aim of our study is to delineate the natural course of the disease to verify endpoints of clinical studies. Methods. A total of 20 infantile patients diagnosed by the collaborative Dutch centers and 133 cases reported in literature were included in the study. Information on clinical history, physical examination, and diagnostic parameters was collected. Results. The course of Pompe’s disease is essentially the same in the Dutch and the general patient population. Symptoms start at a median age of 1.6 months in both groups. The median age of death is 7.7 and 6 months, respectively. Five percent of the Dutch patients and 8% of all reported patients survive beyond 1 year of age. Only 2 patients from literature became older than 18 months. A progressive cardiac hypertrophy is characteristic for infantile Pompe’s disease. The diastolic thickness of the left ventricular posterior wall and cardiac weight at autopsy increase significantly with age. Motor development is severely delayed and major developmental milestones are generally not achieved. For the Dutch patient group, growth deviates significantly from normal despite start of nasogastric tube feeding. Levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, or creatine kinase-myocardial band isoenzyme are typically elevated, although aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase increase significantly with age. The patients have fully deleterious mutations. Acid α-glucosidase activity is severely deficient. Conclusions. Survival, decrease of the diastolic thickness of the left ventricular posterior wall, and achievement of major motor milestones are valid endpoints for therapeutic studies of infantile Pompe’s disease. Mutation analysis and measurement of the α-glucosidase activity should be part of the enrollment program.

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The Natural Course of Infantile Pompe’s Disease: 20 Original Cases Compared With 133 Cases From the Literature

Neither asymmetric septal hypertrophy (ASH), marked cell disorganization in the ventricular septum nor systolic anterior motion of the anterior mitral leaflet (SAM) is pathognomonic of hypertrophic Cardiomyopathy. However, each is uncommonly found in patients with other cardiac disorders and is therefore a highly specific hallmark of hypertrophic cardiomyopathy. Disproportionate septal thickening does occur in about 10 percent of older children and adults with various acquired or congenital heart diseases. In these patients it usually appears to be secondary to the underlying hemodynamic state. However, disproportionate septal thickening is the usual finding in the developing embryonic and fetal heart and it is relatively common (prevalence rate about 25 percent) in normal neonates and infants with congenital heart disease. Likewise, although cell disorganization in the ventricular septum may occur with other cardiac malformations, extensive disorganization is present in about 90 percent of patients with hypertrophic cardiomyopathy and in only about 5 percent of patients with other cardiac diseases. Finally, systolic anterior motion of the anterior mitral leaflet is characteristic of those patients with hypertrophic cardiomyopathy who have obstruction to left ventricular outflow, and it rarely appears (prevalence rate about 3 percent) under basal conditions in other hemodynamic states or cardiac diseases. Hence, in analyses comprising over 1,600 patients the specificity of asymmetric septal hypertrophy, marked septal disorganization and systolic anterior motion of the anterior mitral leaflet was at least 90 percent (90, 93 and 97 percent, respectively). Furthermore, the sensitivity of extensive septal disorganization for hypertrophic cardiomyopathy was 90 percent. The data currently available therefore suggest that the vast majority of patients fulfilling the basic anatomic criteria for hypertrophic cardiomyopathy (that is, a hypertrophied nondilated left ventricle in the absence of a cardiac or systemic disease that itself could produce left ventricular hypertrophy) have a distinct disease entity with diverse clinical manifestations. The majority of such patients appear to have a genetically transmitted disease, but it is not known precisely what proportion of these patients have phenotypically similar but etiologically separate disease entities.

Hypertrophic cardiomyopathy: Recent observations regarding the specificity of three hallmarks of the disease: Asymmetric septal hypertrophy, septal disorganization and systolic anterior motion of the anterior mitral leaflet

In spite of modern obstetric and medical management, the total fetal loss in pregnancies complicated by maternal diabetes mellitus is still appreciably higher than in nondiabetic women. The newborn infant of the diabetic mother shows anatomical and biochemical peculiarities which may be indicative of the mechanisms of fetal wastage operative under these conditions. For this reason, the detailed postmortem findings in a uniquely large series of these infants are reported. Gellis and Hsia1have recently reported on a group of 934 pregnancies among women with diabetes. Of the 721 liveborn infants in their series, 104 died during early infancy. The present report is based on those 95 who were examined post mortem. These infants were delivered at the Faulkner Hospital, Boston, and the Boston Lying-in Hospital, between 1940 and 1956, and include 29 infants described by Warren and LeCompte2and 40 reported by Winter and Gellis.3Because

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=peds&articleId=499675&pdfFileName=archpedi_100_6_004.pdf

Neonatal deaths among infants of diabetic mothers. Postmortem findings in ninety-five infants.

https://vmj.sagepub.com/content/8/1/53.full.pdf

Clinical-pathologic conference.

Employing a clinical approach to the categorization of newborn cardiovascular defects, a list of probabilities has been prepared to aid the pediatrician who is confronted with the common problem of the severely ill newborn heart patient. This study presents the analysis of 155 newborn cardiac autopsies along with 10 surgical successes. These cases were selected from 187 autopsied live-born neonates with major cardiovascular malformations by excluding patients with associated severe non-cardiac disease and major non-cardiac malformations. One-half of the neonatal deaths occurred during the first week with a stepwise decrease in the succeeding weeks. Hypoplastic left heart (rudimentary left ventricle with aortic or mitral stenosis or atresia) was the commonest malformation (37 cases). The second most frequent was complete transposition of the great vessels (25 cases). Most newborns with these two defects died in the first week of life, indicating the urgent need for attention to infants with such anomalies. In contrast, in patients with other malformations, deaths were spread throughout the first month. Neonates who died with combinations of major defects composed the third largest group in this series, emphasizing the difficulties in diagnosis and treatment. Ventricular septal defects, and patent ductus arteriosus were found to be uncommon causes of death or severe distress in the first month of life. As a result of these findings it is evident that a large number of newborns in severe distress from cardiovascular malformations will have defects which are beyond help. However, in many newborn cardiacs, the defects can be relieved or made less severe. Consequently, it is felt by the authors that a newborn infant who is seriously ill due to a suspected cardiac anomaly should be regarded as both a medical emergency and as a potential surgical emergency. Such a patient should be transferred at once to an institution where all facilities and personnel are available for complete investigation and for surgery. Cardiac catheterization and angiocardiography should be performed as soon as the pediatric cardiologist feels that these tests are indicated, often within a matter of hours. This will frequently be in the first days or even in the first twenty-four hours of life. The techniques, problems, and hazards involved in such studies have been presented in detail by Rowe. A maximum of information should be sought inasmuch as the additional risk is usually more than compensated for by the increased accuracy and completeness of the diagnosis. Admittedly, the risk of cardiac catheterization and selective angiocardiography is high in a seriously ill newborn cardiac, perhaps of the order of 5 to 10%, but if this hazard is balanced against the extremely high one of death in a matter of hours or days from the underlying disease, there will be little hesitation about proceeding with the investigation. In certain instances it may be advisable to perform surgery without prior cardiac catheterization and angiocardiography. Such unusual instances involve severely ill newborns in whom the clinical diagnosis seems clear and for whom surgery may be lifesaving. The outstanding example of this is the infant who has the classical findings of pulmonic stenosis with an intact ventricular septum, and who appears to be dying in heart failure. Here the risk of cardiac catheterization may outweigh that of surgery. Other instances include occasional critically ill patients with typical findings of coarctation of the aorta, tetralogy of Fallot, complete transposition of the great vessels, vascular rings, and the rare patent ductus arteriosus in whom the clinical diagnosis is obvious. The authors believe that an aggressive approach to the diagnosis and treatment of the distressed newborn cardiac will substantially improve his chances for survival.

Congenital cardiac anomalies in the newborn. A review of conditions causing death or severe distress in the first month of life.

Primary endomyocardial disease.

An analysis was made of the 23 cases of isolated ventricular septal defects seen at autopsy over a 20-year period at a children's hospital. All of the deaths occurred during the first 15 months of life. In addition to the clinical and morphologic findings, cardiac catheterization data obtained on 6 of the infants are presented. A wide range of electrocardiographic variation with respect to ventricular hypertrophy was found. No simple relationship between the size of the defect and the clinical manifestations could be demonstrated. The surgical implications of the findings are discussed.

Ventricular Septal Defects in the Infant Age Group

In 4 of 16 patients having glycogenoses other than Pompe's disease electrocardiographic abnormalities were found. These abnormalities could not be related to the type of glycogenosis present and were limited to changes in the T wave and the QT interval. No other evidence of heart disease was found in these patients.\n Hemodynamic and cineangiographic evidence of muscular obstruction to cardiac outflow from both right and left ventricles was documented in a case of Pompe's disease. The obstruction was confirmed by postmortem findings. In one other case not investigated by cardiac catheterization, similar autopsy findings were found. This alteration is probably more widespread than is generally known, and has important therapeutic implications.

Cardiac problems in the glycogenoses with specific reference to pompe's disease.

Seventy-five patients who had undergone diagnostic arterial catheterization of the femoral artery by a percutaneous technique were examined for diminished pulse pressure by amplified oscillometric blood pressure recordings. Nine of the 75 (12%) had diminished pulse pressure recordings. These data contrast favorably with our previous experience with arteriotomy for catheterization and indicate that percutaneous femoral arterial catheterization in children has less risk of arterial complication than previously suspected.

Edward C. Lambert

Papers

Congenital cardiac anomalies in the newborn. A review of conditions causing death or severe distress in the first month of life.

Primary endomyocardial disease.

Ventricular Septal Defects in the Infant Age Group

Cardiac problems in the glycogenoses with specific reference to pompe's disease.

Arterial pulses following percutaneous catheterization in children.