Chelation therapy for the treatment of atherosclerosis. An appraisal.
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Biomedical subjects
Publications and source records attributed to J Somerville.
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Sixty-three consecutive patients aged 2 months to 27 years with simple ventricular septal defect (VSD) or the syndrome of Fallot's tetralogy were prospectively investigated with 2-dimensional (2-D) echocardiography to assess the accuracy of the method in defining the anatomic site of the VSD. Twenty-two patients were referred for surgery without invasive investigation. The anatomy was confirmed in all patients at operation. Two-dimensional echocardiography was reliable in identifying subaortic, inlet, small, moderate, and large subtricuspid, large subpulmonary, and most large central and apical muscular VSDs. Mistakes were made initially in distinguishing doubly committed subarterial defects from subaortic VSD because of difficulty in imaging the right ventricular outflow in short axis at the aortic root level, small subpulmonary defects obscured by prolapsed aortic cusp tissue, and small apical or outlet muscular VSDs because of difficulty in distinguishing true "dropout" from trabeculations. Other VSDs particularly muscular, were sometimes overlooked after another large VSD had been identified. Thus, identification of the anatomic site of VSDs by 2-D echocardiography is a reliable method that can replace invasive investigation in assessing the uncomplicated VSD before operation. Ventricular septal defects are classified as muscular or subvalvular and subdivided according to the valve to which the defect is related.
Five patients with clinical features of tetralogy of Fallot had subarterial doubly committed ventricular septal defect (VSD) with absence or deficiency of the infundibular septum. Two-dimensional (2-D) echocardiography differentiated this special group from those with the usual Fallot's anatomy. In addition to the long-axis view of the left ventricle which showed the subaortic VSD and the aortic and mitral fibrous continuity, the short-axis view at the cardiac base clearly demonstrated the subpulmonary extension of the VSD in the atypical group. Two-dimensional echocardiography was found superior to biplane angiography, which in 3 patients suggested the erroneous diagnosis of double-outlet right ventricle with pulmonic valve stenosis. This variant form of Fallot's tetralogy poses special surgical problems.
One hundred twenty patients operated on for closure of a ventricular septal defect (VSD) had postoperative assessment by 2-dimensional echocardiography. The presence of persistent "drop-out" between ventricular septum (VS) and the periphery of the "patch" was considered a sign of detachment and residual shunt. Echocardiographic findings of intact VS or residual VSD were correlated with angiographic findings in 30 patients and with clinical signs in 90 patients. Minute shunts with increased flow ratios less than 1.5:1 were occasionally missed. Persistent small drop-out was sometimes wrongly diagnosed as residual shunt when the patch was in an angled position and in the early postoperative weeks when peripatch edema of the VS suggested drop-out. Thus, 2-dimensional echocardiography is a reliable method for assessing significant persistent ventricular shunts and intact VS after surgical closure of a VSD.
The two-dimensional echocardiographic features of anomalies of systemic and coronary venous return are described as they were seen in 23 patients with this diagnosis proven at angiography. A left-sided superior vena cava draining to the right atrium via an enlarged coronary sinus was correctly identified in all 17 patients with this condition by observing a characteristically moving ovoid structure in the region of the posterior atrioventricular groove. This structure opacified before the right side of the heart following bolus injections of contrast material from a left arm vein. Injection from the right arm in 12 patients or femoral vein in four patients of this group produced contrast echoes within the right heart only. A left-sided superior vena cava draining directly to a left atrium in three patients, or left side of a common atrium in two patients with atrial situs inversus, was identified by the immediate opacification of the left-sided chamber following injection from the left arm. Two patients with hemiazygos inferior vena caval return to the left superior vena cava or left atrium were studied using injections of contrast from the femoral vein which successfully identified the venous abnormality. Two-dimensional echocardiography, when combined with peripheral venous injections of contrast will reliably demonstrate anomalies of systemic venous return, and thus provides important information before more invasive procedures.
Eleven patients with double mitral valve orifice and atrioventricular defects were studied, and the diagnosis proven by open heart surgery. The correct preoperative diagnosis was suggested by a characteristic angiographic appearance of the medial border of the left ventricle. M-mode echocardiography may show the two orifices which are better seen on two dimensional echocardiography. Two operative deaths occurred in patients with a slightly obstructive valve, and one late death followed mitral valve replacement. Eight patients did well after minor repair to a cleft, or leaving the valve untouched. Occasionally a double mitral orifice, if disorganised and slightly stenotic, may cause early deterioration in a patient with an otherwise uncomplicated ostium primum defect. The surgeon should be forewarned of this mitral anomaly since simple repair may be difficult.
Fifty-two of the 56 offspring from 90 patients with proven atrioventricular defects were examined. There were five with congenital heart disease. The defects were concordant in three and discordant in two. The mother was the affected propositus in all cases. In this relatively small sample the incidence of congenital heart disease in the offspring of parents with atrioventricular defects was 9.6%, or 14.3% if only the female propositi were considered. This is a much higher figure than that reported for the simple forms of isolated congenital heart disease.
The long-term follow-up of six patients operated on for aorto-left ventricular communication has been reviewed in detail. All had residual aortic regurgitation after the initial repair of the defect. It was severe in four and required repeated reoperation in three with ultimate aortic valve replacement. The failure of early repair to solve the haemodynamic problem has provoked a reconsideration of the basic anatomy, of the surgical approach, and of the postoperative physiology of this anomaly. The so called "tunnel" is not a tunnel with length but should be considered as a localised breach at the insertion of the right coronary cusp. The localised aortic root dilatation at the site is a weakness that remains after closure of the tunnel leaving a poorly supported aortic valve and a weak root. Thus, the initial repair of the aorto-left ventricular communication must not only close the communication but reinforce, strengthen, and support the right aortic sinus in order to maintain cusp competence.
Between 1970 and 1980 19 patients aged 13 months to 47 years (mean 16 years) had surgical repair of lesions associated with corrected transposition. Four had had previous palliative surgery. Operations were performed for ventricular septal defects in 17 (multiple in two), and in addition 10 had relief of pulmonary stenosis, three had atrial septal defects closed, and three had valve replacement for left atrioventricular valve regurgitation. Two patients had annuloplasty for isolated left atrioventricular valve regurgitation. There was a high operative mortality (37%). Twelve survivors left hospital and were followed up for three to eight years. There is concern about the high incidence of left atrioventricular valve regurgitation and progressive postoperative left sided ventricular dysfunction. Heart block after surgical intervention contributes to this, and careful pacemaker policies are necessary as two late deaths were related to this. Only one patient is asymptomatic and without complications 40 months after operation. These disappointing late results are partly related to the onset of heart block, but it seems that independent systemic ventricular function may deteriorate in some patients. Thus surgical treatment of lesions associated with corrected transposition should be recommended only in those with important symptoms or signs of changing systemic ventricular dysfunction.
Data on 18 patients, aged 12 to 42 years, with documented aortic regurgitation and tetrad of Fallot or pulmonary atresia with ventricular septal defect were reviewed. In two patients, aortic regurgitation was caused by surgical repair but in the others it was present before operation. There was increased volume overload from a long-standing surgical shunt (8 to 30 years' duration) or congenital systemic collateral vessels in 14. Six patients with a history of infective endocarditis had aortic cusp perforations. Failure to detect the presence of aortic regurgitation before radical repair in six patients contributed to operative problems and postoperative morbidity and mortality. Aortic valve surgery was performed in 13 patients. Aortic regurgitation is an acquired complication that should be specifically excluded by routine retrograde ascending aortography in all adolescents or adults with tetrad of Fallot or pulmonary atresia with ventricular septal defect. Earlier radical repair in the first decade of life may prevent the complication.
The ability of two dimensional echocardiography to define right and left ventricular morphology in congenital heart disease was examined in 19 patients with discordant ventricular connections and abnormal relations, but with two ventricles and two unambiguous atrioventricular (A-V) valves. The two dimensional echocardiographic criteria used to identify a chamber as having right morphology were (1) an irregular endocardial surface, (2) insertion of chordae tendineae into the ventricular septum, (3) presence of an infundibulum, (4) a triangular-shaped ventricular cavity, (5) observation of a moderator band, and (6) recognition of the A-V valve as tricuspid. The two dimensional echocardiographic criteria for a left ventricular morphology were (1) a smooth endocardial surface, (2) presence of two discrete papillary muscle groups, (3) an ellipsoid-shaped ventricular cavity, and (4) recognition of the A-V valve as mitral. Identification of the associated A-V valve as mitral or tricuspid was the most reliable criterion, defining each ventricle in all 19 patients. The nature of chordal attachment and papillary muscle insertion successfully identified all left-sided and posteriorly related ventricles and 9 of the 19 anterior ventricular chambers. Other criteria were less useful although, when observed, they confirmed the ventricular type.
Forty-nine consecutive patients, aged 2 to 28 years, were followed after open aortic valvotomy. Three late deaths occurred in relation to reoperation. Seventeen reoperations were performed 2 to 14 years after valvotomy for severe stenosis in 12 patients, aortic regurgitation in three patients, and aortic stenosis and regurgitation in two patients. Among the 12 patients who required reoperation for severe obstruction, five aged over 19 years had calcified valves with normal aortic roots and valve replacement was simple. Seven had tunnel obstruction with a hypoplastic aortic root, constituting a difficult surgical problem, and necessitating total aortic root replacement in four. The postoperative course after simple aortic valvotomy is determined by several factors; the basic pathological form of the obstruction is the most important. Those who present in the first decade with lumpy valves and small aortic roots tend to form a diffuse tunnel obstruction when residual stenosis remains after valvotomy; older patients with pliable domed valves slowly develop calcified cusps and present less problems as the aortic root is usually a good size. Although aortic valvotomy offers good early results with a low mortality, it should be regarded as palliative as all patients will ultimately require reoperation. Younger patients with lumpy valves and a small aortic root have more problems and may require different initial management.
Between 1976 and 1980, 26 patients aged 7 to 36 years had complete replacement of the aortic root with a valved homograft into which the coronary arteries were reimplanted. The main indication was the tunnel type of obstruction combining a hypoplastic valve ring, often with supra and subvalvar stenosis. Nineteen had previous operations for congenital left ventricular outflow obstructions. There was one perioperative death and one late death from progressive pulmonary vascular disease. Relief of left ventricular outflow tract obstruction was achieved in a majority of cases and the valves were entirely competent. With increasing experience, the initial problems of malalignment and torsion of the coronary arteries and complete heart block have been largely overcome. This operation provides an alternative technique for the management of diffuse left ventricular outflow tract obstruction and related problems in young patients. The long-term results of aortic homografts are well documented, and by eliminating the problems of aortic regurgitation it is anticipated that this may represent an advance in treatment.
Five patients with isolated clefts in the anterior leaflet of the mitral valve, unassociated with atrioventricular septal defects, are described. All had significant mitral regurgitation, with the cleft being the only abnormality in three. Two patients had an associated ventricular septal defect, one with a straddling right atrioventricular valve. Angiocardiography in four showed moderate regurgitation, but was not able to delineate the aetiology. Two dimensional echocardiography showed a constant defect in the anterior leaflet, pointing towards the left ventricular outflow tract. This differed from 30 cases with atrioventricular septal defects where the "cleft" pointed towards the interventricular septum and was situated between the anterior and posterior bridging leaflets. All cases with isolated clefts had surgical correction, with minimal residual regurgitation on follow-up examination in two cases. Our current policy in patients with uncomplicated isolated cleft involves non-invasive assessment of these children and surgical correction if the regurgitation is significant.
Three patients who had closure of an ostium primum defect developed severe fixed subaortic stenosis requiring surgical removal three to 11 years late. In two, the basic anatomy of the attachment of the superior portion of the anterior mitral cusp and submitral apparatus predisposed to the formation or deterioration of this complication. Both had subvalvar gradients and angiographic narrowing of the outflow tract in systole and diastole. In the third patient the strut of the Hancock prosthesis used to replace a double orifice mitral valve impinged on the outflow tract to stimulate the formation of a serious fixed obstruction. Subaortic gradients before operation must be specifically looked for, particularly in those with the characteristic radiological deformity of the submitral apparatus, and at operation the subaortic region must be inspected. Postoperatively the search for developing subaortic stenosis must include regular M-mode and 2-dimensional echocardiography, and cardiac catheterisation may be required. Although a rare complication, subaortic stenosis is a progressive and damaging lesion which requires early recognition and treatment despite the apparent well-being of the patient.
Thirty-nine consecutive patients, aged 5 to 57 years, were followed for two to 15 years with serial haemodynamic studies after removal of fixed subaortic stenosis, which was never a "membrane". Two late deaths occurred, one sudden and one in congestive failure. Of 37 survivors, 25 were asymptomatic and could be classified as good or excellent if judged by well-being. Seven were symptomatic, two having had reoperation for fixed subaortic stenosis, and four needed long-term pacing. Evaluation, including the effect of isoprenaline, showed important dynamic obstruction in 17, five of whom redeveloped fixed obstruction. Seven had congestive features without outflow gradients, and 14 had neither congestion nor outflow obstruction. Complete assessment therefore confirmed that only 14 (36%) were haemodynamically satisfactory; two of them had permanent pacing, and four had had aortic valve surgery. Fixed subaortic stenosis should be removed early, when diagnosed, and completely before secondary myocardial changes occur. Patients however "well" need regular supervision and early haemodynamic assessment. The aortic valve, whether repaired, replaced, or untouched, remains a site for infective endocarditis for life. The fixed subaortic stenosis removed at operation may not be present in that form at birth, but acquired secondary to other congenital abnormalities which remain in the patient.
A 65-yr-old woman presented with severe congestive cardiac failure and physical signs of an atrial septal defect. Investigation by cardiac catheterisation and cross-sectional echocardiography showed a persistent left superior vena cava draining through an enlarged coronary sinus into the right atrium. In addition, the left atrium was connected to the coronary sinus by two defects in its lateral wall. The atrial septum was intact. The physiological result of this rare anatomical abnormality was a large left-to-right shunt with a small right-to-left component. The defects were closed surgically.
Calcification of aortic homografts used for reconstruction of the right ventricular outflow tract was studied in assess the frequency of occurrence, location, extent, speed of progression, and clinical and hemodynamic implications. Radiologic follow-up by means of penetrated posteroanterior and lateral radiograms ranged from 2 to 10 years in two groups of patients. Group 1 comprised 40 patients with cyanotic congenital heart disease in whom an aortic homograft was used to restore continuity between the right ventricle and pulmonary arteries. Results from this group were correlated with those from Group 2, which included 80 patients who had a homograft implanted as a substitute for their own pulmonary valve, which had been used as an autograft for replacing the diseased aortic or mitral valve. In Group 1, 92% of the grafts were calcified 6 months to 4 years after operation. Calcification was severe in two cases, moderate in 33, and mild in two. One of the grafts had to be removed in the tenth postoperative year for progressive obstruction. In Group 2, 27% showed signs of calcification, never before the second year after implantation. Calcium development was severe in two, moderate in 12, and mild in eight. Two obstructed homografts were removed. Aortic homograft calcification has been more common, developed earlier, and been more severe in patients operated upon for congenital lesions. The lower age, the peculiar metabolism, the distorted anatomy, and the development of pulmonary hypertension in this group may account for this fact. In 96% of the patients who were followed, calcification has not yet meant clinical disability or hemodynamic dysfunction. Use of "fresh," antibiotic-sterilized homografts has reduced the incidence of calcification in Group 2 and is expected to decrease its severity in all cases.