Leonard C. Blieden

Cardiac valvular anomalies in Fabry disease. Clinical, morphologic, and biochemical studies.

SUMMARY The cardiovascular abnormalities were Investigated in two unrelated hemizygous males with Fabry disease who had clinical mitral insufficiency. Postmortem examination of their hearts revealed anatomic, ultrastructural and biochemical abnormalities resulting from defective activity of the lysosomal enzyme, a-galactosidase A. The ultrastructural and biochemical studies demonstrated the marked accumulation of the major glycosphingolipid substrate, trihexosyl ceramide, in the lyosomes of all the cardiac tissues examined; the greatest concentrations were found in the mitral valve and left ventricular myocardium. Intriguingly, digalactosyl ceramide, a glycosphingolipid substrate not detectable in normal lung, vessel or cardiac tissues, was found increased only in the lung and right heart tissues. Morphologic and chemical examination of cardiac and systemic vessels demonstrated accumulation of trihexosyl ceramide in lysosomes of the vascular endothelium. These studies demonstrate that the progressive accumulation of trihexosyl ceramide in the lysosomes of the cardiac structures and vascular system leads to the multiple cardiovascular manifestations of Fabry disease.

Coronary atherosclerosis and myocardial infarction associated with systemic lupus erythematosus.

Summary In a 29-year-old woman with systemic lupus erythematosus, death was the result of acute myocardial infarction associated with extensive coronary atherosclerosis. The first of two myocardial infarcts was identified at 27 years of age. None of the recognized underlying factors for premature atherosclerosis was identified. An association between lupus and atherosclerosis has previously been reported in a limited number of cases.

Cardiac involvement in Sandhoff's disease. Inborn error of glycosphingolipid metabolism.

Abstract Two siblings with Sandhoffs disease manifested clinical and laboratory evidence of significant cardiomyopathy. Postmortem examination of the hearts of both patients revealed anatomic, biochemical and ultrastructural abnormalities resulting from deficient activities of the enzymes hexosaminidase A and B. A study of the biochemical and ultrastructural changes in the hearts revealed the accumulation of the glycosphingolipid globoside in all cardiac tissues. The necropsy findings indicate that Sandhoffs disease should be considered in the differential diagnosis in infants with cardiomyopathy or mitral insufficiency.

Aorticopulmonary septal defect. An experience with 17 patients.

Seventeen patients with aorticopulmonary septal defect were studied over a period of 1S years. This report includes clinical, electrocardiographic, radiographic, cardiac catheterization, and angiocardiographic data on the patients. Clinical examination usually showed a large left-to-right shunt and significant pulmonary hypertension. A definitive diagnosis was made by cardiac catheterization and angiography in I2 patients. The presence of a systolic ejection click in 5 patients and a right aortic arch in 3 was a diagnostic help and may differentiate aorticopulmonary septal defect from persistent ductus arteriosus. The catheter position at the time of haemodynamic study was also of diagnostic importance. Associated lesions were present in 9 patients, and corrected in 4 patients. Twelve patients underwent surgery: complete bypass and moderate total body hypothermia were used in ii patients. Four patients underwent postoperative haemodynamic studies.

A Developmental Complex Including Supravalvular Stenosis of the Aorta and Pulmonary Trunk

A developmental complex is described characterized by (1) supravalvular stenosis of the aorta and pulmonary trunk, (2) dysplasia of valves and (3) stenosis of ostia of coronary arteries and branches of the aortic arch. From the four cases described, it is evident that not all of the features of the complex need be present in a given case and, when present, some lesions are not of functional significance. The variations underly the potential for differences in the hemodynamic states of affected subjects.

Prosthetic Valve Replacement in Children: Results in 44 Patients

Abstract This report presents an experience with 44 children, including 9 less than 5 years of age, who were operated upon for replacement of a cardiac valve. Our early operative mortality was 60%, whereas in the past 4 years it has been only 30%. We have operated only on significantly symptomatic children for whom no other therapy was available. From our experience, we cannot judge the necessity of anticoagulants. No patients have required a second operation because the valve has been outgrown, although several patients who underwent mitral valve replacement have had postoperative gradients across the prosthesis.

Analysis of the P wave in congenital cardiac malformations associated with splenic anomalies

Abstract The anatomic and ECG features of 23 patients with polysplenia and 17 patients with asplenia were reviewed. Patients with polysplenia tended to have a superiorly oriented P wave axis. In asplenia the P wave axis was inferiorly directed, but not in the normal location. We were unable to correlate the abnormal P wave axis with specific anatomic features of the atria.

Cardiac tumours in tuberous sclerosis

Sir: We recently began to measure total plasma homocysteine in patients being treated for homocystinuria (cystathionine synthase deficiency). The patients were treated with a low methionine diet and/or pyridoxal phosphate. The method that we used was that of Vester and Rasmussen [1]. With this method the normal values for plasma total homocysteine are between 7 and 16 gmol/1. We compared these results with results obtained by measuring free homocystine and the mixed disulphide of homocystine/cystine using an amino acid analyser. The results were quite striking. In many cases, the total plasma homocysteine level rose to about 50 gmol/1 before any increase in plasma free homocystine or its mixed disulphide with cystine could reliably be detected on the amino acid analyser system. In some patients, total plasma homocysteine levels of about 20 gmol/1 did demonstrate free homocystine or the mixed disulphide but in most patients the total plasma homocysteine levels needed to be at least 50 gmol/1 (about 4 times the upper limit of the control range) before any free plasma homocystine was detected. In our experience most clinicians who wish to rule out a diagnosis of homocystinuria usually request only a plasma or urine amino acid assay as the preliminary screening test and this means that only free homocystine or its mixed di-sulphide with cystine can be detected. We feel that our data on patients treated for classical homocystinuria may have relevance to the detection of this disease in suspected patients. In our opinion measurement of plasma total homocysteine is the preferred way to screen for patients with any of the forms of homocystinuria. This would avoid the possibility that there are some mild cases of homocystinuria which may not be detected when we use only an amino acid analyser to detect free homocystine. It seems appropriate to bring this to the attention of other investigators working in the field of inborn errors of metabolism. We look forward to learning of the experience of others. Reference

Carbon dioxide fiberoptic laser for treatment of coarctation of the aorta

Much research is currently being undertaken to develop laser techniques for the treatment of acquired cardiovascular diseases.l There is only one preliminary report of the potential application of argon laser for congenital heart disease, including treatment of coarctation of the aorta in the newborn.2 In the present report, the use of a flexible CO, laser catheter for the potential treatment of coarctation of the aorta in children is described. Segments of the descending aorta including a severely coarcted area were removed during repair of coarctation of the aorta by end-to-end anastomosis in two boys (1 ‘/z and 3-years old, respectively). The segments were immersed in 0.9% saline solution at a temperature of 4” C. The laser irradiation was performed 24 hours later in room air. The CO, laser source was an Apollo model 580. An optical fiber of 0.9 mm in diameter that was produced by extrusion of silver chloride-silver bromide crystals through suitable dyes at an elevated temperature was inserted into a regular No. 6 French cardiovascular catheter. The distal tip of the catheter with the optical fiber was positioned perpendicularly and in contact with the coarctation membranes, which were approximately 1 to 2 mm in thickness. No manual pressure was applied to the catheter. Pulsed laser irradiation was performed with a mean power output of 2.3 W at the tip of the catheter for periods of 0.6 second, until dissolution of the membranes was achieved, as judged by the formation of new lumens about 4 x 5 mm and 3 x 4 mm in diameter (Fig. 1). In the first case we used 12 pulses and in the second 15 pulses. In some instances a single pulse perforated the membrane. In other instances, several pulses were necessary to create a perforation. The whole procedure took us less than 2 minutes. The histopathologic examination of the aortic segments revealed a thick muscular septum crossed by a central irregular lumen, lined by a thin layer (30 to 40 mm in width) of carbonized material (Fig. 2). The subjacent area showed a delicate cribriform pattern surrounded by relatively few necrotic cells and eosinophilic threads. The remaining myocytes in the coarctation membrane as well as the aortic wall were almost unaffected, and beyond 0.3