Nonobstructive coronary thrombosis in sudden cardiac death

Careful histologic studies were performed on the coronary arteries, myocardium and conduction system of the hearts of six men aged 32 to 44 years who died suddenly with no history of heart disease. All six hearts demonstrated coronary atherosclerosis without evidence of complete obstruction or myocardial Infarction. A nonobstructing mural coronary thrombus was found in all six hearts; in four, the thrombus was located in the left anterior descending coronary artery. Distal microthrombi were found in four hearts.In these six men, the terminal event, often a ventricular arrhythmia, may have been related to the mural coronary thrombus. Small fragments originating from such lesions can obstruct the microcirculation producing sudden lethal arrhythmias. Nonobstructing mural coronary thrombosis may be more prevalent and more significant than previously suspected and should be considered In cases of sudden cardiac death.     

Lipid metabolism in perfused human and dog coronary arteries.

The paper represents a summary of our studies in which in vitro perfusion of human and animal coronary vessels was carried out. Formation and uptake of lipids in perfused human coronary arteries were studied under a vairety of experimental conditions, including exposure to carbon monoxide. The effect of collagenase on lipid synthesis and transport in carotid arteries of dogs was also studied. Human plasma with hydrogen-3-labeled cholesterol and carbon-14-acetate was used to perfuse human blood vessels. Autologous plasma was employed. Inhibition of cholesterol uptake was accomplished by the addition of 7-ketocholesterol (concentrations of 0.005 to 1 mum/ml) to the perfusate. Both atherosclerotic and normal human coronary arteries incorporated 14C-acetate into lipids but failed to synthesize either cholesterol of cholesterol esters. Similar results were obtained in human saphenous veins perfused at arterial pressure. Cholesterol uptake from the perfusion fluid was demonstrated in atherosclerotic and normal human coronary arteries as well as in human saphenous veins. Carbon monoxide increased permeability of the arterial wall to cholesterol uptake. In dog arteries exposed to collagenase marked increases in cholesterol uptake were found, but total lipid synthesis was reduced; the relative synthesis individual lipids remained unchanged. The addition of 7-ketocholesterol to the perfusate reduced cholesterol uptake by the vessel by 90 percent. Inhibition of cholesterol uptake was present in all species and was not due to oxidation of cholesterol to 7-detocholesterol in the perfusate. The results illustrate that human coronary arteries as well as human saphenous veins synthesize lipids but not cholesterol. Cholesterol flux into the artery is augmented by carbon monoxide and collagenase. The data also show that active inhibition of cholesterol uptake in the arterial wall can be accomplished by competitive inhibition with 7-ketocholesterol.     

Echocardiography in aortic root dissection and dilatation.

Six patients with aortic root dissection proved by angiography, surgery or autopsy, and six patients with aortic root dilatation were studied by echocardiography. Echocardiography was diagnostic in five or six patients with dissection and suggestive in the sixth, disclosing anterior and posterior dissection in three, anterior dissection in one and posterior dissection in one. The recording of a double echo in the aorta was the diagnostic feature. Angiography was diagnostic in four of the six patients, yielded a false negative result in one and was not performed in one. Six patients with dilatation had an enlarged aortic root by echocardiography. Left ventricular size, stroke volume, ejection fraction, aortic regurgitant flow and velocity of circumferential fiber shortening were calculated in 11 patients. Echocardiography was extremely helpful in the diagnosis, management and follow-up in patients with aortic dissection or dilatation.     

Medical screening of patients with coronary artery disease. Criteria for entrance into exercise conditioning programs

Although considerable emphasis has been placed on stress testing and physical training of patients with coronary artery disease, data on safe and thorough preliminary medical evaluation are scarce. Because the routine history and physical examination are not sufficient to protect the exercising subject, medical screening attempts a thorough analysis of the patient's motivation, physical status, possible risk factors and the probability of benefit.Motivation is a critical factor since training for prolonged periods of time at high levels of heart rate and oxygen consumption may be required. Patients who have unstable angina or who may be harmed by increased myocardial oxygen requirements must be excluded. Concomitant influencing diseases and certain medications may also be causes for rejecting a patient. Valvular heart disease and severe systemic hypertension are not associated with benefit from exercise conditioning. The screening physician must exclude patients with certain abnormal electrocardiographic patterns, such as bilateral bundle branch block and type II second degree atrioventricular block, and he must be assured that he is dealing with coronary artery disease, not a pathologic process that mimics it. When these principles are applied, few persons in organized programs of exercise conditioning should suffer, and the yield of good results should be enhanced.     

Eosinophilia and endomyocardial fibrosis.

A 12 year old boy died after a 3 year course of recurrent and progressive heart failure. His cardiac symptoms began with a marked leukocytosis (white blood cell count 188,500/mm3) due to eosinophilia (90 percent). In 6 months, the leukocytosis and eosinophilia subsided, but the patient's heart failure progressed over the next 2 1/2 years. At autopsy there was no evidence of leukemia, but a severe endocardial fibrosis extending into the myocardium was found. The origin of endomyocardial fibrosis, although unknown, appears to have been related to the eosinophilia in this patient.     

Mitral valve early diastolic closing velocity in the echocardiogram: relation to sequential diastolic flow and ventricular compliance.

Uncertainty exists regarding the determinants of mitral valve early diastolic closing velocity (E-F slope) in the echocardiogram. Accordingly, the mitral E-F slope, sequential atrioventricular flow in each third of diastole in the cineangiogram and an index of ventricular compliance (delta volume/delta pressure normalized by end-diastolic volume) were obtained in 10 normal subjects, 10 patients with coronary artery disease and marked dyssynergy and 9 patients with hypertrophic cardiomyopathy. The E-F slope of 103 +/- 20 mm/sec (mean +/- standard deviation) in normal subjects was greatly reduced in patients with coronary artery disease and hypertrophic cardiomyopathy (54 +/- 22 and 27 +/- 16 mm/sec, respectively, P less than 0.001). Transmitral flow of 52 +/- 25 cc during the initial third of diastole in normal subjects represented 48 +/- 10 percent of total flow and was diminished in patients with coronary artery disease and hypertrophic cardiomyopathy: 23 +/- 16 cc (25 +/- 24 percent) and 24 +/- 20 cc (20 +/- 11 percent), respectively (both P less than 0.001). The ventricular compliance index in normal subjects of 0.064 +/- 0.02 was also decreased identically in patients with coronary artery disease and hypertrophic cardiomyopathy: 0.029 (both P less than 0.001). The E-F slope was correlated with transmitral flow during the first third of diastole (r = 0.87) but was decreased to a slightly greater extent for any given reduction in flow in patients with hypertrophic cardiomyopathy than in patients with coronary artery disease. Although the E-F slope could not be related to compliance in individual patients, patients with an E-F slope of less than 75 mm/sec nearly always had diminished compliance. Thus, mitral E-F slope is primarily related to transmitral flow in the initial third of diastole. Reduced ventricular diastolic compliance usually results in diminished flow, and thus a decreased E-F slope, in patients with coronary artery disease or hypertrophic cardiomyopathy. The greater reduction in E-F slope for any decrement of flow in hypertrophic cardiomyopathy than in coronary disease may be due either to interference with vortex streaming or to alterations in the relation of the papillary muscles to the mitral valve induced by altered ventricular geometry; the finding indicates that factors in addition to flow may influence the E-F slope.     

Echocardiographic assessment of the severity of aortic stenosis in children and adolescents.

The magnitude of ventricular hypertrophy in response to afterloading is determined by wall stress, with wall thickness increasing in proportion to ventricular load until systolic wall stress is normalized. With use of echocardiographic measurements of left ventricular end-systolic wall thickness (Ws) and cavity transverse dimension (Ds), the pressure constant k was calculated in 16 patients without left heart obstruction according to the formula k = P-Ds/Ws. The mean value for k was 225 +/- 6.7 (standard deviation) mm Hg. From this value, left ventricular pressure was estimated in 13 patients with aortic stenosis aged 4 to 17 years using the formula P = k-Ws/Ds. No subject had evidence of cardiac failure. Peak systolic aortic pressure difference (delta P) was calculated by subtracting cuff-measured brachial arterial peak systolic pressure from the estimated left ventricular pressure. Excellent correlation was obtained between the estimated delta P and that found at cardiac catheterization (r = 0.89). In two patients, echocardiographic data predicted significant obstruction in the presence of normal electrocardiographic, vectorcardiographic and vector lead tracings. Echocardiography offers a noninvasive method for estimating the severity of aortic stenosis, in the absence of myocardial failure; it appears to be more sensitive than other currently employed techniques.     

Echocardiographic manifestations of discrete subaortic stenosis

The echocardiographic manifestations of discrete membranous subaortic stenosis are described in three cases. The diagnosis was confirmed by cardiac catheterization in all and at operation in two. The characteristic finding in these patients was abnormal movement of the aortic valve leaflets. The leaflets opened rapidly with the onset of systole, then exhibited abrupt premature closure shortly after ventricular ejection. The valve remained partially closed throughout the remainder of systole. This premature leaflet closure Is believed to be caused by obstruction to aortic valve flow produced by the band-like fibrous subaortic tissue. The valve leaflets also exhibited a gross fluttering motion possibly caused by a jet stream effect of the turbulent blood hitting the leaflets. In the two patients treated surgically, postoperative echograms continued to show premature leaflet closure but the degree of closure was decreased. The echocardlogram of one patient had the characteristic systolic anterior bulge of the mitral valve observed in muscular subaortic stenosis or idiopathic hypertrophic subaortic stenosis. Our data suggest that the following echocardiographic findings are suggestive if not specific for discrete subaortic stenosis: aortic valve closure early in systole, persistent valve closure throughout the remainder of systole, coarse fluttering of the leaflets, and absence of asymmetric septal hypertrophy.     

Effect of direct revascularization surgery on coronary collateral circulation in man.

In 63 consecutive patients with significant coronary artery disease (more than 75 percent stenosis), the effects of direct myocardial revascularization on coronary collateral channels were studied 6 to 29 days (mean 13.4 days) after operation. Collateral vessels were identified preoperatively and their angiographic regression or reappearance after operation was noted. In 15 patients (23 percent), there was no evidence of collateral flow before or after operation. The remaining 48 patients had 186 collateral channels preoperatively. Postoperatively, 84 (45 percent) of these collateral vessels were no longer apparent, 75 (40 percent) were unchanged and 27 (15 percent) were identical with the preoperative vessels but the pattern of blood flow was reversed. The findings suggest that in the presence of established collateral channels, direct revascularization acutely alters existing flow and pressure gradients in a complex manner. Collateral channels disappear or remain unchanged when a gradient is decreased or maintained; collateral flow is reversed when a gradient is increased. These data may permit (1) objective preoperative estimation of distal vessel runoff in vessels with collateral channels, and (2) evaluation of the completeness of revascularization in assessing long-term postoperative results.     

Echocardiographic features of primary pulmonary hypertension

Echocardiograms were recorded in nine patients with primary pulmonary hypertension proved at cardiac catheterization. A reduced diastolic slope of the anterior mitral valve leaflet, simulating mitral stenosis but with normal motion of the posterior leaflet, was observed in all patients. Other features found included a large right ventricular dimension (nine patients), a small left ventricular dimension (three patients), a thick interventricular septum (six patients), systolic mitral leaflet prolapse (four patients) and abnormal septal motion (four patients). The last feature was most probably due to secondary tricuspid or pulmonic insufficiency, or both. The finding of a decreased mitral valve slope, often used as a criterion for mitral stenosis, should not be accepted alone as proof of mitral stenosis; the posterior mitral valve leaflet echo must be carefully searched for and identified. This echo is often difficult to identify, but the normal motion of this structure found in all patients excludes the diagnosis of mitral stenosis as a cause for the pulmonary hypertension.     

Critical analysis of clinical factors in estimating severity of aortic valve disease

Clinical data were analyzed in a group of 79 patients with aortic stenosis or combined aortic stenosis and insufficiency by the usual methods and by discriminant function analysis. It was possible to predict the level of aortic-left ventricular gradient (above or below 50 mm Hg) from signs and symptoms in approximately 83 percent of patients. The analyses performed yielded insight into the significance of the various commonly presenting symptoms in these lesions. For example, the slope of the carotid upstroke, calcium in the valve, T wave inversion and a large thrusting left ventricular impulse all indicated a high peak gradient, whereas syncope did not contribute to the separation of values. Heart failure made an insignificant contribution to prediction of the level of gradient.     

Acute aortic arch dissection: reevaluation of the indications for medical and surgical therapy.

Of 42 patients with dissection of the aorta, 4 had important arch involvement. Results were good in 2 patients treated medically. In two other patients wrapping the arch with a Dacron graft successfully prevented fatal hemorrhage. This technique avoids the need for arch replacement in selected cases. From this experience and a review of others a flow sheet was developed to guide decision-making in the surgical and medical management of patients with aortic dissection.     

Acute coronary embolism complicating bacterial endocarditis: operative treatment.

A patient with bacterial endocarditis and no previous history of angina substained an acute anterolateral myocardial infarction while awaiting surgery. Selective coronary arteriography revealed a filling defect in the left anterior descending coronary artery with limited flow beyond the area of occlusion. A calcific embolus from the infected aortic valve was removed at the time of valve replacement, and the patient had an uneventful immediate postoperative course. Late postoperatively paravalvular aortic regurgitation recurred before and after a second repair.     

Pseudomalfunction of a Beall mitral valve prosthesis in the presence of paravalvular aortic regurgitation.

Premature closure of a Beall mitral valve prosthesis is described in a patient with aortic prosthetic paravalvular regurgitation. Differentiation from valvular malfunction and diagnostic confirmation by means of cinefluoroscopy and simultaneous electrocardiography are discussed.     

Echocardiographic findings in Uhl's anomaly. Demonstration of diastolic pulmonary valve opening.

The echocardiographic findings in a case of Uhl's anomaly, or congenital hypoplasia of the right ventricular myocardium, are reported. Diastolic opening of the pulmonary valve is described. Comparison is made with echocardiograms in Ebstein's disease of the tricuspid valve, and it is suggested that echocardiography can help in differentiating these two entities. In addition to the pulmonary valve finding, increased right ventricular dimension, delayed tricuspid closure and abnormality (prolapse) of the mitral valve were noted. The echocardiographic findings are compared with cardiac catheterization data.     

Cardiac catheterization in small infants: the percutaneous approach.

Cardiac catheterization of small infants can be performed by the percutaneous technique using materials readily available from commercial sources. Twenty infants averaging 3.0 kg (range 1.3 to 4.1 kg) underwent percutaneous sheath cardiac catheterization in a 12 month period. After refinement of the technique, cardiac catheterization in all small infants was attempted percutaneously with a 90 percent rate of success. This percutaneous approach has distinct advantages for the small infant because it is performed rapidly, preserves venous integrity and has a low rate of morbidity.     

Echocardiographic abnormalities in acute rheumatic fever.

The echocardiographic velocity of circumferential fiber shortening and left atrial dimension were measured serially in two groups of children with acute rheumatic fever: Group I, six patients with valve regurgitation without congestive heart failure, and Group II, seven patients with regurgitation and congestive heart failure. In Group I, the initial velocity of circumferential fiber shortening was increased to 1.90 +/- 0.31 circumferences per second (circ/sec) (mean +/- standard deviation). In group II, it was decreased (1.18+/-0.25). In group I velocity of circumferential fiber shortening subsequently decreased but remained above the normal level; in Group II it increased to exceed the expected normal value. Concurrent changes in left atrial dimension were observed in both groups. The initial left atrial dimension of Group I (2.2 +/- 0.75 cm/m2) was slightly increased and returned to normal (1.70 +/- 0.32) on follow-up study. The left atrial dimension of Group II was greatly increased initially (2.70 +/- 0.81 cm/m2) and remained large (2.50 +/- 0.67). Three patients in Group II experienced rebound during corticosteroid withdrawal. In each the velocity of circumferential fiber shortening decreased, suggesting impaired cardiac contractility. The echocardiogram thus facilitates serial assessment of the severity of carditis in acute rheumatic fever.     

Echocardiographic recognition of paraseptal structures

Improved echocardiographic equipment provides detailed images of the heart and shows anatomic paraseptal structures previously not well defined. Echocardiograms were analyzed from 33 patients who later underwent cardiac transplantation, and the paraseptal structures noted were correlated with the pathologic specimens. Patterns associated with right ventricular chordae tendineae, the moderator band and the posterior papillary muscle are illustrated. Hypertrophic and fibrotic right ventricular trabeculae and left ventricular paraseptal bands are noted. These structures can be specifically sought and identified using the current generation of echocardiographs, thereby avoiding potential problems of septal definition and measurement.