Tissue valve replacement of prosthetic heart valves for thromboembolism

Twenty-five patients who had repeated thromboemboli from a prosthetic mitral valve were treated with reoperation using a tissue valve prosthesis. Reoperation was performed an average of 4.0 years after the original valve replacement in 14 men and 11 women, with an average age of 50 (range 35 to 65) years. A stented allograft was used in the first 7 patients and a porcine xenograft in the last 18 patients. There were one hospital death and two late deaths. With the first prosthetic valve there were 66 documented embolic episodes in 101.5 patient years (0.65 embolus/year). Only four embolic episodes in 67.4 patient years (0.059 embolus/year) occurred after tissue valve replacement (P < 0.001). These results indicate that in patients with recurrent or severe embolization after prosthetic heart valve replacement, rereplacement with a tissue prosthesis can be safely performed and significantly reduces the likelihood that additional embolic episodes will occur.     

Correlative study of regional left ventricular histology and contractile function.

In 110 patients with documented coronary artery disease, transmural biopsy of the anteroapical region of the left ventricle was performed during aortocoronary bypass grafting. Biopsy specimens were semiquantitatively graded microscopically for myocardial fibrosis as an indicator of chronic ischemic damage. Preoperatively, systolic wall motion of the region from which the biopsy specimen was taken was semiquantitatively graded as showing normal motion, hypokinesia, akinesia or dyskinesia on ventriculography. Wall motion-histologic correlations, taking into account both electrocardiographic evidence of anterior infarction and ST-T abnormalities, were then established. Overall, there was fair agreement (72 percent) between functional and histologic assessment of the left ventricular region evaluated, both qualitatively (normal versus abnormal, 72 percent agreement) and quantitatively (degree of abnormality, correlation coefficient 0.66, P = 0.005). The 22 patients with electrocardiographic evidence of anterior infarction had various degrees of abnormal regional motion and myocardial fibrosis. Discordance between wall motion and histologic findings was most common (50 percent of instances) in the 34 patients with anterior ST-T changes without infarction and generally was manifest as abnormal motion with normal histologic features. By contrast, normal motion and abnormal histologic features represented the most common type of discordance (22 percent of instances) in the 54 patients without either anterior infarction or ST-T deviation. These data provide a basis for inference of myocardial morphologic features (fibrosis) from assessment of ventriculographic wall motion and the electrocardiogram. They may thus be useful in predicting the potential functional benefits of bypass grafting of coronary arteries supplying abnormally contractile segments of the left ventricle.     

Surgical treatment of degenerative mitral regurgitation

Between October 1965 and April 1975, mitral valve replacement was performed In 66 patients with myxomatous degeneration of the mitral valve (“floppy valve syndrome”). Operative mortality was 6 percent (four patients). Current evaluation was obtained for all patients; the average postoperative follow-up interval for surviving patients was 3.5 years (range 1 month to 9.9 years); the total duration of postoperative follow-up for all patients was 180 patient-years. Overall survival rates, calculated by the actuarial method, were 81, 68 and 50 percent, respectively, 1, 2 and 5 years after mitral valve replacement.Preoperative variables with a significantly adverse effect on patient survival included patient age greater than 50 years, New York Heart Association functional class IV, left ventricular end-diastolic pressure greater than 12 mm Hg and mean pulmonary arterial wedge pressure greater than 16 mm Hg. Support is advanced for the concept that mitral valve dysfunction associated with myxomatous degeneration constitutes a broad spectrum of clinicopathologic involvement. Acute clinical and hemodynamic deterioration may often occur in the setting of chronic mitral valve dysfunction. Postoperative mortality is directly related to preoperative functional disability and hemodynamic evidence of impaired left ventricular function. Consideration should be given to earlier operative intervention in patients with myxomatous mitral degeneration and mitral insufficiency before severe and probably irreversible impairment of ventricular function occurs.     

Mitral and aortic valve orifice area in normal subjects and in patients with congestive cardiomyopathy: Determination by two dimensional echocardiography

Previous determinations of normal valve orifice areas have been mainly from postmortem studies. In this study mitral and aortic valve orifice area were determined from two dimensional echocardiograms in 20 normal subjects and 20 patients with congestive cardiomyopathy. Mitral valve orifice area was larger than quoted in standard textbooks. Both mitral and aortic valve orifice area were reduced in patients with cardiomyopathy. Valve opening was assessed relative to left ventricular and aortic root size. The ratio of mitral valve orifice area to left ventricular cross-sectional area was markedly reduced in patients with cardiomyopathy compared with normal subjects. The ratio of aortic valve orifice area to aortic root size also was reduced in patients with cardiomyopathy.Anterior mitral leaflet E point-septal separation was similar to that in previous reports contrasting normal subjects with patients with myopathy. Among patients with cardiomyopathy, mitral E point-septal separation was primarily a function of left ventricular size and was not significantly correlated with fractional shortening or ejection fraction within this group having uniformly poor systolic function.     

Small vessel disease of the heart resulting in myocardial necrosis and death despite angiographically normal coronary arteries.

A 46 year old man who had undergone cardiac transplantation 1 year previously had progressive congestive heart failure without evidence of cardiac rejection. Cardiac catheterization and angiography revealed a reduced ejection fraction and cardiac output caused by diffuse left ventricular hypokinesia, but the epicardial coronary arteries were widely patent. The transit time of injected contrast material across the coronary arterial tree was greatly slowed. Within a few days cardiogenic shock and death occurred. The large epicardial coronary vessels were grossly patent at autopsy, although nonstenosing arteriosclerotic plaques were identifiable histologically. However, intramyocardial vessels showed severe arteriosclerotic narrowing, resulting in multiple, diffuse microinfarcts.     

Growth and tissue abnormalities in young people with cyanotic congenital heart disease receiving systemic-pulmonary artery shunts

The effects of systemic-pulmonary artery shunts on growth, body composition, and adipose tissue were studied in 29 children, aged 2 to 16 years, with cyanotic congenital heart disease. Of these, 16 received surgical shunts and 13 were unoperated. Postoperatively, all patients who received shunts were better oxygenated (systemic oxygen saturation 69 ±11% preoperatively and 84 ± 4% postoperatively; mean ± standard error of the mean) and were symptomatically improved. However, the groups were not significantly different in height, weight, lean body mass, total body fat, $\text{lean}\text{fat}$ ratio, cellular lipid content, or total number of lipid-con-taining fat cells. Age at operation did not seem to influence the effects of surgery. These observations suggest that growth and certain measurements of tissue development were unaffected by surgical systemic-pulmonary artery shunts despite increased oxygenation and symptomatic improvement after operation.     

Hemodynamic effects of sublingual nifedipine in acute myocardial infarction

Twenty-six patients with acute myocardial infarction (mean delay time 6 hours after onset of symptoms) were randomized to control or nifedipine treatment (10 mg sublingually, followed by 10 mg every 6 hours for a total of 24 hours). Nifedipine reduced arterial blood pressure from 127/78 to 115/70 mm Hg at 30 minutes (p < 0.001) and continued to reduce the blood pressure significantly for 12 to 18 hours. Nifedipine also reduced systemic vascular resistance and the rate-pressure product. Cardiac output increased from 4.9 liters/min before nifedipine to 5.4 liters/min at 60 minutes (p < 0.05 vs controls). In patients with high initial pulmonary wedge pressures, sublingual nifedipine decreased the wedge pressure (p < 0.001) more effectively than did 80 mg of furosemide given intravenously. Thus, nifedipine may be useful in patients with early myocardial infarction and left ventricular failure.     

Limitations of comparing left ventricular volumes by two dimensional echocardiography,myocardial markers and cineangiography

Measurement of left ventricular volume at end-diastole or end-systole with both two dimensional echocardiography and either Cineangiography or radionuclide scans, not recorded simultaneously, has shown large echocardiographic underestimation of volumes even in normal ventricles. In this study fluoroscopic and two dimensional echocardiographic recordings were obtained in 18 patients with abnormal wall motion and previously implanted myocardial markers. The echocardiographic values for volume and those derived from myocardial markers correlated well (r = 0.87), and there were no statistically significant differences in values obtained with the two methods at end-diastole or end-systole. The ejection fractions obtained with two dimensional echocardiography (mean ± standard deviation 46 ± 7 percent) and with fluoroscopic recording of the markers (41 ± 9 npercent) did not differ statistically.These results were compared with those in another 18 patients (nine with abnormal wall motion) having two dimensional echocardiography within 24 hours of a 30 ° right anterior oblique contrast left ventriculogram. Again, two dimensional echocardiographic ventricular volume correlated well with the angiographic volume (r = 0.85), although echocardiographic end-diastolic volume was consistently 20 percent less than angiographic end-diastolic volume (p < 0.01). Ejection fraction obtained with echocardiography (47 ± 8 percent) was less than that obtained with angiography (60 ± 7 percent) (p < 0.001). Interobserver variability in calculating volume with echocardiography was 4 percent.Probable reasons for the lack of severe underestimation of volume with echocardiography even in very abnormal ventricles, relative to that demonstrated in prior reports, include improvements in ultrasonic beam width, tracing method, transducer position and scan plane orientation within the ventricle. In addition, the possible effects of angiographic dye in the ventricular trabeculae are discussed and the effect of simultaneous studies by two different methods are compared.     

Randomized comparison of intravenous versus intracoronary streptokinase for myocardial infarction

The efficacy of intravenous (i.v.) thrombolytic therapy has not been firmly established in comparison with the intracoronary (i.c.) route of administration. In a randomized trial of 28 patients who underwent angiography before and during i.v. and i.c. administration of Streptokinase (STK), recanalization was achieved in 73% of patients who received the drug by the i.c. route, compared with 62% of patients who received the drug by the i.v. route (difference not significant). Reopening took 28 minutes for i.c. STK and 39 minutes for i.v. STK. Patients in whom recanalization was successful using either route of administration had shorter euglobulin lysis times and lower fibrinogen levels than did patients in whom it was not successful (p < 0.05). Bleeding complications were closely correlated with heparinization after thrombolysis rather than with STK itself. These results in a limited patient series suggest that early administration of i.v. STK in the emergency department may yield recanalization rates similar to those for the i.c. route and may benefit myocardial preservation by restoring flow much earlier.     

Nature of inducible ventricular tachyarrhythmias in a canine chronic myocardial infarction model

A canine model suitable for serial conscious studies was developed to evaluate the nature of sustained ventricular tachyarrhythmias in chronic experimental myocardial infarction. Thirteen dogs underwent left anterior descending coronary artery ligation followed by complete reperfusion; 11 sham-operated dogs served as controls. In this model, ventricular tachyarrhythmias are inducible in most dogs with experimental infarction and in several dogs without this condition. The morphologic features, rate and drug response of the induced arrhythmias are unlike those of human ventricular tachycardia. Tachyarrhythmia induction is facilitated by anesthesia and thoracotomy. This canine infarct model does not adequately imitate human recurrent ventricular tachycardia, but may simulate human sudden cardiac death.     

Results of intraventricular baffle procedure for ventricular septal defect and double outlet right ventricle or d-transposition of the great arteries

Thirty patients with ventricular septal defect and d-transposition of the great arteries or double outlet right ventricle underwent placement of an intraventricular baffle to achieve physiologic correction. Eighteen of these patients also required an external conduit to establish continuity between the right ventricle and the pulmonary artery. There was an overall 22 percent early mortality rate, although the rate was 63 percent in patients who weighed less than 10 kg. There was an additional 20 percent late mortality rate, primarily related to conduction disturbances and pulmonary vascular obstructive disease, problems that have not occurred in patients operated on since 1974. Of the survivors, all are asymptomatic and as a group have achieved a significant weight gain. Many have residual hemodynamic abnormalities that required cardiac catheterization for precise assessment. Four patients have been reoperated on, with no additional mortality.     

Calcification of aortic versus mitral porcine bioprosthetic heart valves: a radiographic study comparing amounts of calcific deposits in valves explanted from the same patient

Calcium detected by radiography was compared in 10 pairs of aortic and mitral glutaraldehyde-treated porcine bioprosthetic heart valves explanted from 10 patients (7 men and 3 women), aged 19 to 68 years (mean 43). Both valves of 6 pairs of valves had undergone primary tissue failure (revealed by cardiac catheterization and angiography) and 1 valve of the other 4 pairs of valves had undergone primary tissue failure. These porcine valves had been implanted from 2 1/4 to 9 years (mean 5 3/4). All 20 explanted valves contained calcium. The grade of calcium was the same in 4 pairs of valves (grade 2+ or 3+), and 1 grade different in 4 pairs of valves (grade 1+ to 4+), with the greater calcium evenly divided between the 2 valve positions. There was more than 1 grade greater mitral valve calcium in 2 pairs of valves (grade 3+ and 4+ mitral vs 1+ and 2+ aortic, respectively). Thus, calcium is usually present in both aortic and mitral valve positions when bioprosthetic valves of this type in either valve position fail as a result of primary tissue failure, and radiographic calcium in porcine bioprosthetic valves is usually similar in grade in both the aortic and mitral valve positions.     

Acute retrograde dissection of the ascending thoracic aorta.

The clinical, aortographic and pathologic features of six patients with acute retrograde dissection of the ascending thoracic aorta are presented and appropriate guidelines for surgical treatment are proposed. Although acute dissection of the aorta was the clinical diagnosis in these patients, clinical features were not helpful in identifying the pattern or extent of dissection. Aortography demonstrated that the site or sites of intimal tear occurred adjacent to the origin of the innominate artery (three patients) or left subclavian artery (two patients); an intimal tear was not seen in one patient. Five of the six patients also had acute or chronic (or both) antegrade dissection of the descending thoracic aorta. Retrograde dissection of the ascending aorta occurred in the outer portion of the media. The primary histologic changes were fragmentation of elastic fibers and fibrosis of the media. Three patients died, including two of the five patients who were treated surgically; the other three patients survived. Immediate replacement of the ascending aorta with a Dacron graft is recommended to prevent lethal complications due to extension of retrograde dissection, even though dissection may involve both the ascending and descending aorta and the site of intimai disruption may not be resected. The aortic arch or descending thoracic aorta, or both, can be replaced later, utilizing total body hypothermia and temporary circulatory arrest, if further dis-section or enlargement of the aorta occurs after emergency operation on the ascending aorta.     

Single and two dimensional echocardiographic features of the interatrial septum in normal subjects and patients with an atrial septal defect.

The interatrial septum is one of the least studied structures in M mode echocardiography. Two dimensional echocardiography has made it possible to record simultaneous M mode and two dimensional echocardiograms. Such studies were performed in 10 normal subjects and in 9 patients with a secundum atrial septal defect. In the short axis view of the base of the heart, the interatrial septum was visualized in the two dimensional studies as a linear echo running from the posterior aortic wall to the posterior atrial wall and in the M mode records as a series of dense echoes posterior to the aorta. The great variability in echo dropout of the interatrial septum made it impossible to distinguish the normal subjects from the patients with atrial septal defect. The dense echoes of the interial septum in the M mode records gave the false impression that they were filling the left atrium. These data indicate that (1) a secundum atrial septal defect cannot be reliably differentiated from a normal septum using these echocardiographic methods, and (2) the medial location of the interatrial septum should be appreciated so that it will not be confused with a left atrial mass.     

Two dimensional echocardiographic quantification of infarct size alteration by pharmacologic agents.

In 27 closed chest dogs left ventricular wall motion abnormalities assessed quantitatively with two dimensional echocardiography were used as a measure of myocardial infarct size, and the change in extent of segmental wall motion abnormalities due to drug intervention early after infarction was evaluated. The extent of wall motion abnormalities was measured with echocardiography before and at 20 and 40 minutes and 5 1/2 hours after coronary occlusion. Three subgroups of dogs received, respectively, an infusion of nitroglycerin, phenylephrine or saline solution. Infarct size was measured with technetium pyrophosphate scintigraphy of the excised left ventricle. The infarct size correlated well with the extent of wall motion abnormalities before death. Wall motion was initially similar among the three groups but was significantly improved after treatment with nitroglycerin (P less than 0.025), remained stable with continued saline infusion and worsened significantly (P less than 0.05) after treatment with phenylephrine. Two dimensional echocardiography can be used to quantify experimental canine myocardial infarction and assess the effect of nitroglycerin.     

Methionine intolerance: a possible risk factor for coronary artery disease

Homocystinuria, an inherited disorder associated with premature atherosclerosis, represents a severe form of methionine intolerance. To analyze the importance of milder forms of methionine intolerance in the genesis of vascular disease, the relation between provokable methionine intolerance and coronary artery disease was investigated. In a group of 138 men, aged 31 to 65 years (mean 53), referred for cardiac catheterization, plasma homocystine was measured before and 6 hours after an oral l-methionine load (0.1 g/kg). Thirty-nine subjects found to have normal coronary arteries had a mean post-load plasma homocystine level of 0.59 +/- 0.37 mumol/liter. A criterion at the 95th percentile (1.64 SD above the mean) was selected and applied to the remaining 99 subjects with coronary artery disease (0.70 +/- 0.68 mumol/liter). Sixteen (16%) of 99 subjects with coronary artery disease exceeded this level as compared with 1 (2%) of 39 subjects without coronary artery disease (p less than 0.04). The risk of coronary artery disease in men with provokable methionine intolerance was increased sevenfold as estimated by the odds ratio. By correlation matrix and multivariate regression analyses, provokable homocystinemia was predictive of coronary artery disease and was independent of tobacco smoking, hypertension, diabetes mellitus, serum cholesterol and age. It is proposed that men with mild methionine intolerance exposed to the high methionine content of the Western diet may develop intermittent homocystinemia and thus may be at greater risk for the development of coronary artery disease.     

Two-dimensional echocardiographic assessment of bioprosthetic valve dysfunction and infective endocarditis

Two-dimensional echocardiography of Hancock porcine heterograft valves was evaluated by correlation with clinical, hemodynamic, angiographic and pathologic findings in 80 patients. Ninety-five aortic and mitral bioprostheses were categorized by the type of valvular abnormality: group I, dysfunction due to primary tissue failure (41 valves); group II, dysfunction due to paravalvular leakage without infection (5 valves); group III, infective endocarditis with or without hemodynamic dysfunction (28 valves); and group IV, control cases without dysfunction or infection (21 valves). Increased size of a bioprosthetic leaflet image (minimal dimensions 3 x 5 mm) was observed in 46% (19 of 41) of cases with primary tissue failure and in 62% (10 of 16) of cases with leaflet vegetations due to endocarditis. Prolapse of leaflet echoes to below the level of the bioprosthetic sewing ring occurred in 76% (28 of 37) of cases with torn leaflets and also in 46% (6 of 13) of valves with vegetations on intact leaflets. Antegrade extension of leaflet echoes to beyond the level of the stents, observed in 4 of 16 cases with leaflet vegetations, was the only echocardiographic sign distinguishing leaflet infection from leaflet degeneration. Aortic bioprostheses with ring dehiscence affecting 40 to 90% of the anular circumference showed motion discordant with the motion of the adjacent aortic root and native anulus. Although echocardiographic abnormalities are frequently observed with bioprosthetic leaflet degeneration or infection, the echocardiographic appearance often does not distinguish between these two major complications and is best interpreted concurrently with other clinical and laboratory assessment.     

Conduction disturbances related to the site and severity of mitral anular calcification: A 2-dimensional echocardiographic and electrocardiographs correlative study

To investigate an apparent association of mitral anular calcium (MAC) and electrocardiographic abnormalities, the relation between location of 2-dimensional (2-D) echo-quantified MAC and conduction disturbances was studied in 140 patients with MAC (MAC group) and in 135 age- and sex-matched patients without MAC (control group). The MAC group was subclassified regarding site and severity of calcium in the mitral anulus. The site of MAC was defined as Type I, near the primary conduction system—MAC located in the medial segment and/or extending to the anterior mitral leaflet; and Type II—MAC located at the central and/or lateral segments away from the primary conduction system. The severity of MAC was graded on 2-D echocardiography as mild (localized within 1 segment) and moderate to severe (> 1 segment).

Seven patients with MAC, and only 1 control subject, had pacemakers in place. Conduction disturbances were present in 44 (31%) of 140 patients with MAC, and in 37 (27%) of 135 control patients (difference not significant). But there were more conduction disturbances in patients with Type I MAC (53%) than in those with Type II MAC (26%) (p < 0.01). Specifically, complete left bundle branch block and intraventricular conduction delay were more prevalent when MAC was near the conduction system. Conduction disturbances also were more prevalent in patients with Type I MAC than in the control group: intraventricular conduction delay (Type I, 12% versus control, 4%; p < 0.05) and total conduction disturbances (53 versus 28%; p < 0.01). These data suggest that moderate to severe degrees of MAC located near the conduction system are associated with conduction disturbances, especially intraventricular conduction delay.     

The isolated human epicardial coronary artery

Ring segments from coronary arteries from recipient hearts of patients receiving cardiac transplants were prepared and mounted in an organ bath. Spontaneous contractile activity, factors that affect basal tone, agonist-induced contractile responses, regional receptor distribution, activity of cardioactive drugs, and species differences were studied. Agents that mediate contraction include histamine, acetylcholine, norepinephrine, potassium and some prostaglandins. Calcium-entry blockers, nitrates and beta-adrenergic agonists caused relaxation. Major species differences exist in coronary vascular pharmacology. Ring segments from human epicardial coronary arteries are suitable for pharmacologic studies, and because of species differences, they offer an ideal model for investigating the pharmacology of the human coronary circulation.