Catherine A. Neill

Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study.

The Baltimore-Washington Infant Study is a population-based case-control study that seeks to identify risk factors for cardiovascular malformations. Between 1981 and 1986, a total of 2102 infants with cardiovascular malformations were ascertained, among whom 271 (12.9%) also had a chromosome abnormality. Among 2328 random control subjects, only two had a chromosome abnormality. Down syndrome with cardiovascular malformations had a maternal age-adjusted regional prevalence of 4.33/10,000 for the white population and 3.70/10,000 for the nonwhite population. Endocardial cushion defect, the predominant cardiac abnormality in Down syndrome (60.1%), rarely occurred as an isolated cardiac lesion (2.8%). The absence of transpositions and the rarity of heterotaxias and of right- and left-sided obstructive lesions in trisomies indicate that there may be a genetic influence on specific embryologic mechanisms. Alimentary tract lesions were more common in Down syndrome than among euploid patients with heart disease and more severe than in control subjects. Urinary tract lesions also occurred in excess of the rate in control subjects. The coexistence of these major malformations with heart disease raises the possibility of incomplete expression of the VA(C)TER (vertebral, anal, cardiac, tracheal, esophageal renal) association. The selective association of chromosome abnormalities with certain cardiovascular defects is now beginning to be explained by reported embryologic studies on cellular characteristics. An explanation of the negative association with transposition and obstructive lesions requires further multidisciplinary studies on genetic and epigenetic factors.

Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.

We studied a boy who presented at age 3 1/2 years with cardiomegaly, a distinctive electrocardiogram, and a history of a brother dying with cardiomyopathy. From age 3 1/2 to 5 years, cardiac disease progressed, resulting in intractable congestive heart failure. Skeletal muscle weakness developed and a muscle biopsy showed lipid myopathy. Muscle and plasma carnitine were reduced to 2 and 10% of the normal mean values, respectively. Therapy with L-carnitine (174 mg/kg/da) was begun at age 5 1/2 years and continued to the present (age 6 1/2 years). The cardiac disease has resolved and the muscle strength has returned to normal. Plasma carnitine concentrations have risen to the low-normal range, while urinary carnitine excretion has increased to values which are 30 times normal. The renal clearance of carnitine exceeds normal at all plasma concentrations and plasma carnitine values do not change acutely after an oral carnitine load. These results suggest that there is a distinct form of carnitine deficiency which presents as cardiomyopathy and may be successfully treated with L-carnitine. A defect in renal and possibly gastrointestinal transport of carnitine is a likely cause of this patients disorder.

Sudden death among postoperative patients with tetralogy of Fallot: a follow-up study of 243 patients for an average of twelve years.

SUMMARY Two hundred and forty-three patients were evaluated following total correction of tetralogy of Fallot with special emphasis on postoperative conduction disturbances and on the occurrence of sudden death. The average follow-up period was 12 years with a range of 61/2; to 16½h years.Sudden death occurred in seven patients. Four deaths were among those with right bundle branch block pattern (RBBB) and three of the four had premature ventricular contractions (PVC) for more than one month postoperatively. PVCs were documented in ten of the 158 patients with RBBB; sudden death occurred in three (30%). Three of the ten (30%) patients with trifascicular block pattern (TB) died suddenly, while no deaths occurred in 24 patients with bifascicular block pattern (BB). Progression of RBBB to BB and TB occurred in 18 patients from one month to seven years postoperatively (58% of BB and 40% of TB). The risk of sudden death in patients with RBBB and PVCs following tetralogy repair is high and warrants consideration of suppressive therapy. TB also carries a high risk. The finding that RBBB may progress to BB or TB mandates long-term careful follow-up of all tetralogy patients with postoperative conduction disturbances.

Asplenia syndrome : insight into embryology through an analysis of cardiac and extracardiac anomalies

Asplenia syndrome is characterized by complex congenital heart defects, asplenia and abdominal heterotaxy. Recent interest in the syndrome has been increased by new knowledge arising from animal models and by continuing improvements in surgical outcome in childhood. To further elucidate the embryologic timing and mechanisms of the asplenia syndrome, 32 necropsy cases were reviewed and 487 published autopsy cases were reanalyzed at the hospital. The most common congenital heart defects were atrial septal defects, common atrioventricular canals and conotruncal anomalies. With use of current information on the timing of normal development, it was hypothesized that most defects originate at Streeter Horizon XIII; patients averaged 3.2 Horizon XIII defects, more than at any other stage. Distribution was unimodal. Extracardiac anomalies also exhibited a developmental spectrum. Because the normal spleen develops by Horizon XIII, asplenia, the sine qua non of the syndrome, originates then or earlier. Abnormal pulmonary lobation occurred in 80% of cases, with right isomerism occurring most often; pulmonary branching asymmetry also originates at or before Horizon XIII. Abdominal heterotaxy occurred in 72% of cases, but the timing of origin is unclear. Anomalies of other systems, including genitourinary, musculoskeletal, endocrine, and nervous systems, develop later (typically XV to XXIII); specific anomalies were less frequent, although much more prevalent than in the general population. It is concluded that asplenia syndrome is a focal developmental disturbance in laterality which occurs primarily at Horizon XIII.

The Direction of Blood Flow in Anomalous Left Coronary Artery Arising from the Pulmonary Artery

An infant with anomalous origin of the left coronary artery from the pulmonary artery is presented, and the problem of the direction of blood flow in the anomalous vessel is discussed. Determinations of arterial pressure and oxygen saturation in the blood of the anomalous artery have demonstrated that the blood in this vessel flowed in a retrograde manner. It is concluded that in this condition oxygenated blood flows from the aorta into the normal right coronary artery and passes through collateral branches into the left coronary artery with ultimate drainage of the blood into the pulmonary artery. Ligation of the anomalous coronary artery with concomitant de-epicardialization appears to be a rational and effective method of therapy. For maximal effectiveness the operation should be performed prior to the onset of irreversible changes, and emphasis is placed upon the importance of early diagnosis and prompt treatment.

Left Atrial Ectopic Rhythm in Mirror-Image Dextrocardia and in Normally Placed Malformed Hearts Report of Twelve Cases with "Dome and Dart" P Waves

T HE CARDIAC ACTIVATION normally arises in the head of the sinus node and the relation of the right atrium to the left determines the direction of the P wave in lead I: the P wave is upright in normal subjects and in dextroversion of the heart, whereas the P wave is negative when the atria are inverted as in mirror-image dextrocardia. The direction of the P wave in lead I has generally been considered2A6 as diagnostic of the position of the atria; this concept has been reinforced by the fact that concomitant atrial hypertrophy usually does nlot alter in a significant manner the projection of the resultant atrial vector on lead 1.7 Even in the presence of nodal rhythm the direction of the P wave in lead I has been believed to be a reliable indication of atrial position.8 9 Our experience suggests, however, that the diagnostic value of these criteria has been overemphasized. Recent observation of a patient with dextroversion and proved normal atrial position who presented permanently negative P waves in lead I10 prompted a study of atrial activation in 22 patients with clinical diagnosis of mirror-image dextrocardia. This study revealed that in 14 cases, or in 64 per cent, the P waves were positive in lead I; in all but two of these patients the inversion of the atria was established by angiocardiography, surgery, or both. Further observation

Asplenia syndrome—Risk factors for early unfavorable outcome☆

As medical and surgical management of congenital heart disease in infancy continues to improve, severe and complex defects are increasingly recognized as the source of mortality and long-term morbidity. The asplenia syndrome has a very poor prognosis; indeed, in 1962, Roberts and associates1 stated that “the finding of asplenia and situs inversus in a patient with congenital heart disease virtually precludes…corrective or even palliative surgical procedures.” As part of a study of embryologic timing of the syndrome,2 we reviewed 519 autopsy cases in an attempt to define risk factors associated with early unfavorable outcome.

Long-Term Evaluation of Tetralogy Patients with Pulmonary Valvular Insufficiency Resulting from Outflow-Patch Correction Across the Pulmonic Annulus

In the operative correction of tetralogy of Fallot with a severely narrowed right ventricular outflow tract, widening of the pulmonic annulus is frequently necessary to prevent a high residual pressure gradient and to reduce right ventricular pressure overload. This can be accomplished by incising the pulmonic annulus and inserting a patch graft across the valve, but this usually results in pulmonary valvular insufficiency.Of 426 patients who underwent total correction of Fallots tetralogy between 1959 and 1970, 63 required a patch across the pulmonic annulus. The mortality rate for this group was 30.1%, compared with a total mortality among the 426 patients of 18%. The high mortality rate is influenced by the fact that the majority were corrected in the early years of the series.Fifteen patients were restudied by cardiac catheterization and cineangiography an average of 9.1 years after total correction. Twelve patients were asymptomatic and three patients had only mild symptoms on exertion in spite of angiographically significant pulmonic regurgitation. The average right ventricular systolic pressure was 40 mm Hg; right ventricular end-diastolic pressure was 7 mm Hg; and the right ventricular/pulmonary arterial peak systolic pressure gradient was 14.9 mm Hg. This experience suggests that after a more difficult immediate postoperative period, patients who have right ventricular outflow reconstruction with patches across the pulmonic ic annulus tolerate their chronic pulmonic regurgitation very well.

Negative P Waves in Lead I in Dextroversion: Differential Diagnosis from Mirror-Image Dextrocardia With a Report of a Successful Closure of a Ventricular Septal Defect in a Patient with Dextroversion Associated with Agenesis of the Right Lung

The electrocardiographic differentiation of dextroversion from mirror-image dextrocardia has frequently been based on the configuration of the P waves in lead I, the assumption being that P waves are upright in dextroversion and inverted in mirror-image dextrocardia. A patient is presented with inverted P waves in lead I in whom an electrocardiographic diagnosis of dextroversion was made based on the analysis of the unipolar leads. This diagnosis was confirmed at surgery when a ventricular septal defect was successfully repaired. The Sodi-Pallares method of analysis of the precordial leads is valuable in determining whether the left ventricle lies anteriorly and to the left as in dextroversion or posteriorly and to the right as in mirror-image dextrocardia. Because of the frequency of unusual atrial rhythms in patients with right-lying hearts, the configuration of the P waves is often unreliable. When there is a discrepancy between the result of analysis of atrial activation and that of ventricular activation, the latter should be used in determining whether dextroversion or mirror-image dextrocardia is present.

Permanent Cardiac Pacemakers in Children: Technical Considerations

Placement of permanent cardiac pacemakers in children presents technical problems that are not encountered in the adult. Problems unique to pacemaker implantation in children are related to the patients size, the relative bulkiness of pulse generators, the lack of subcutaneous tissue, and the childs growth and long life expectancy. Based on our experience with implantation of 27 permanent cardiac pacemakers in 13 children, we have found that the use of small pulse generators, placement of epicardial leads, insertion of properitoneal pulse generators, and use of recharabeable pacemakers are satisfactory methods in children.