Showing papers in "American Journal of Cardiology in 1976"

Problems in echocardiographic volume determinations: Echocardiographic-angiographic correlations in the presence or absence of asynergy

Abstract: The relation of minor and major axes of the left ventricle was determined in 100 left ventriculograms performed in the right anterior oblique projection. This relation taken over a wide range of volumes was used to derive a theoretically correct equation for determination of ventricular volume by echocardiography. The final equation was: V =[7.0/2.4 +d] (D3), where V = volume and D = the echocardiographically measured internal dimension. In 12 patients without asynergy, this equation accurately and directly calculated end-systolic and end-diastolic volumes whether the left ventricle was small or large. However, in 12 patients exhibiting left ventricular asynergy the correlation between angiographically and echocardiographically determined volumes was poor. Thus, caution is recommended in the use of time-motion echocardiography to calculate ventricular volumes in patients with coronary artery disease and possible left ventricular asynergy.

A general cardiovascular risk profile: the Framingham Study

Abstract: Persons at high risk of cardiovascular disease can be effectively identified from a measurement of their serum cholesterol and blood pressure, a smoking history, an electrocardiogram and a determination of glucose intolerance. One general function for identifying persons at high risk of cardiovascular disease is also effective in identifying persons at risk for each of the specific diseases, coronary heart disease, atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication, even though the variables used have a different impact on each particular disease. The 10 percent of persons identified with use of this function as at highest risk accounted for about one fifth of the 8 year incidence of coronary heart disease and about one third of the 8 year incidence of atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication. Hence the function provides an economic and efficient method of identifying persons at high cardiovascular risk who need preventive treatment and persons at low risk who need not be alarmed about one moderately elevated risk characteristic.

Clinical efficacy of amiodarone as an antiarrhythmic agent

Abstract: Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 of 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.

Clinical significance of coronary arterial ectasia

Abstract: In a study group of 2,457 consecutive patients undergoing cardiac catheterization, 30 patients had coronary arterial ectasia, an irregular dilatation of major vessels up to seven times the diameter of branch vessels. The frequency of hypertension, abnormal electrocardiogram and history of myocardial infarction was greater than that in a control group with obstructive coronary artery disease. Patients with ectasia did not differ from patients with obstructive disease in sex, age, prevalence of angina or presence of metabolic abnormalities. Six deaths occurred in the group with ectasia during a mean follow-up period of 24 months (annual rate of 15 percent). Extensive destruction of the musculoelastic elements was evident, resulting in marked attenuation of the vessel wall. The short-term prognosis in this group is the same as in medically treated patients with three vessel obstructive coronary artery disease.

Some lessons in cardiovascular epidemiology from Framingham.

Abstract: Epidemiologic investigations have provided a portrait of the potential candidate for coronary heart disease. This is important because studies of the evolution of coronary disease in the general population reveal that it is a common disease that frequently attacks without warning, can be silent in its most dangerous form and can present with sudden death as the first symptom. Progress in identifyin- persons in jeopardy and the factors needing correction makes it theoretically possible to interrupt the chain of factors that eventuate in this disease. Coronary disease does not really begin with crushing chest pain, pulmonary edema, shock, angina or ventricular fibrillation, but rather with more subtle signs like a poor coronary risk profile. The risk factors can be treated quantitatively as ingredients of a cardiovascular risk profile and their joint effect estimated. An efficient practicable set of variables for this purpose is a casual blood test for cholesterol and sugar, a blood pressure determination, an electrocardiogram and a cigarette smoking history. With this set of variables the risk of coronary heart diseases can be estimated over a 30-fold range and 10 percent of the asymptomatic population identified in whom 25 percent of the coronary disease, 40 percent of the occlusive peripheral arterial disease and 50 percent of the strokes and congestive heart failure will evolve. The periodic use of the electrocardiogram at rest and after exercise in persons with a poor risk profile can demonstrate persons with asymptomatic ischemic cardiomyopathy due to advanced coronary artery disease. Most cases of angina pectoris or myocardial infarction represent medical failures; the conditions should have been detected years earlier for preventive management. About 30 percent of patients with infraction will shortly experience new angina, have an annual death rate of 4 percent and a fourfold increased risk of sudden death. Reinfarction will occur at an annual rate of 6 percent, and half the recurrences will be fatal. Congestive heart failure must be expected at 10 times and strokes at 5 times the rate found in the general population. Although no major innovations are required to identify candidates for coronary disease and to estimate their risk, we have much to learn about motivating changes in behavior to control risk factors. Approaches to prevention of coronary heart disease include public health measures to alter the ecology in favor of cardiovascular health, preventive medicine directed at highly vulnerable candidates and hygienic measures initiated by an informed public in its own behalf.

Left ventricular compliance: mechanisms and clinical implications.

Abstract: Left ventricular diastolic compliance is determined by the level of operating pressure and the diastolic pressure-volume relation. This relation is curvilinear and the slope of a tangent (operative chamber stiffness) to the pressure-volume curve increases as the chamber progressively fills. Such preload-dependent changes in compliance occur during any acute alteration in ventricular volume. At a given diastolic pressure, operative chamber stiffness (or its reciprocal, operative chamber compliance) is determined by the relative values for ventricular volume and muscle mass and by the stiffness of a unit of myocardium. Thus, there may be a leftward shift of the diastolic pressure-volume curve (increase in the modulus of chamber stiffness) as a consequence of ventricular hypertrophy or an increase in the stiffness of heart muscle itself (increase in modulus of muscle stiffness). To distinguish between hypertrophy and stiff muscle, it is useful to examine the modulus of chamber stiffness, derived from pressure-volume data, together with the volume/mass ratio of the ventricle. In this fashion, changes in the modulus of chamber stiffness that are inappropriate for a given volume/mass ratio may be attributed to changes in the material properties of the heart muscle. Examples of clinical and experimental pressure-volume studies are presented to illustrate the variety of mechanisms by which acute and chronic changes in ventricular chamber compliance evolve during the course of clinical heart disease. The pathophysiology of pulmonary congestion is best understood by considering the factors responsible for producing changes in chamber stiffness of the ventricle, whereas an examination of muscle stiffness is likely to provide more insight into the extent of irreversible functional and structural defects of the myocardium.

Multivariate prediction of coronary heart disease during 8.5 year follow-up in the Western Collaborative Group Study.

Abstract: The Western Collaborative Group Study is a prospective study of 3,154 employed men aged 39 to 59 years. Ischemic heart disease occurred in 257 subjects during 8.5 years of follow-up. Risk of coronary heart disease was studied with use of the multiple logistic risk model. The incidence of coronary heart disease had a highly significant association with serum cholesterol level, behavior pattern, cigarette smoking and systolic blood pressure in younger (39 to 49 years) and older (50 to 59 years) men and also with age and corneal arcus in the younger group. Type A behavior pattern was strongly related to the incidence of coronary disease in both age groups, independent of interrelations of behavior patterns with any other risk factor.

Myocardial bridging and milking effect of the left anterior descending coronary artery: normal variant or obstruction?

Abstract: Of 5,250 patients undergoing coronary arteriography over a 5 year period, 27 (0.51 percent) had an intramyocardial segment of the left anterior descending coronary artery producing a milking effect or constriction of the artery during systole. Of these, 11 patients with otherwise normal coronary arteries were studied. Hemodynamic data, coronary sinus blood flow and myocardial lactate extraction were measured during atrial pacing at rates of 120 and 150 beats/min and during a 60 watt supine ergocycle exercise test. The degree of narrowing of the left anterior descending coronary artery during systole was graded 3 (greater than 75 percent), 5 patients; 2 (50 to 75 percent), 4 patients; and 1 (less than 50 percent), 2 patients. Four patients with a grade 3 milking effect had S-T depression in the electrocardiogram indicating anterior wall ischemia and lactate production during pacing at 149 ± 2 (mean ± standard error of the mean) beats/min. Three patients had severe angina during pacing. Two patients with a grade 2 milking effect had angina-like chest pain and electrocardiographic changes during pacing at 150 beats/min. However, lactate extraction was unchanged during pacing. Two patients with a grade 1 milking effect had no angina and no electrocardiographic or metabolic abnormalities. Coronary sinus blood flow increased significantly with pacing and ergocycle exercise in all patients (rest 118 ± 8 ml/min; pacing at 150 beats/min 219 ± 27 ml/min; ergocycle exercise 251 ± 17 ml/min) (P < 0.001). We conclude that a grade 3 milking effect observed at coronary arteriography can result in significant obstruction of the left anterior descending coronary artery with typical angina and anterior wall ischemia during tachycardia. Surgical periarterial muscle resection or bypass of the left anterior descending coronary artery might be considered in symptomatic patients with this rare anomaly.

Dynamic changes in left ventricular wall thickness and their use in analyzing cardiac function in the conscious dog.

Abstract: The thickness of the left ventricular free wall and internal chamber diameter were continuously measured by pairs of ultrasonic crystals together with left ventricular pressure in normal conscious dogs. During the resting state, wall thickness decreased abruptly with the onset of atrial contraction from 10.5 mm to an average end-diastolic valueof9.8 mm. In contrast to most previous studies, there was no change in wall thickness during isovolumic systole, and with ejection the wall thickened by 31.3 percent of end-diastolic wall thickness. Atrial pacing, phenylephrine, isoproterenol and propranolol produced significant changes in chamber size with reciprocal changes in wall thickness. In addition, changes in the extent and velocity of left ventricular chamber shortening in the minor equator were associated with comparable reciprocal changes in the extent and velocity of free wall thickening (correlation coefficients 0.97 to 0.99). During acute coronary occlusion, progressive reductions in the extent and velocity of regional wall shortening with partial ischemia were associated with comparable changes in systolic wall thickening characteristics (r = 0.96 and 0.95), and holosystolic elongation in fully ischemic areas was associated with holosystolic wall thinning. During chronic pressure overload, despite wall thickening, the relation between chamber shortening and wall thickening were retained and direct computation of dynamic wall stress variations was possible. These measurements allowed precise definition of the dynamics of the left ventricular wall during normal and abnormal cardiac states. The demonstration that in the absence of regional dysfunction analysis of wall thickness in a single region of ventricular free wall can be used to describe myocardial and overall left ventricular function, as well as regional function in the presence of ischemia, constitutes a new approach to the assessment of cardiac function that has potential for echocardiographic applications.

High sodium-low potassium environment and hypertension.

Abstract: The high sodium-low potassium environment of civilized people, operating on a genetic substrate of susceptibility, is the cardinal factor in the genesis and perpetuation of "essential" hypertension. The noxious effects begin in childhood, when habits of excess salt consumption are acquired at the family table, and are perpetuated by continuing habit and by increasing use of convenience and snack foods with artificially high concentrations of sodium and low levels of potassium. Present methods of food preparation leach out the protective potassium. Extradietary sodium chloride is a condiment not a requirement. Some primitive populations clearly preferred potassium chloride to sodium chloride. Chronic expansion of extracellular fluid volume induced by excess salt consumption causes the central and peripheral circulatory regulatory mechanisms to work at cross purposes, resulting in increased arterial pressure. The protective effect of potassium is dramatic and easily demonstrable in animals and man but its mechanism is not known. It cannot be entirely a direct effect on blood pressure because rats protected with extra potassium against a moderately high salt intake live much longer than control rats but have the same elevated blood pressures. In hypertension with a demonstrable "cause," the high sodium-low potassium environment makes a bad matter worse. In nature, feral man and his forebears were not confronted with excessive sodium and deficient potassium; indeed, the reverse was the case. Evolution has provided powerful mechanisms for conserving sodium and eliminating potassium, but no efficient physiologic mechanisms for conserving potassium and eliminating excess sodium. Most laboratory animal "control" diets contain an amount of sodium that fully suppresses aldosterone secretion, and the same is true of the "average" diet of the American people. Inadequate attention to dietary sodium and potassium makes many studies in both animals and man of uncertain validity. Internally, essential hypertension is an exceedingly complex mosaic of physiologic interactions. Viewed from outside, it is a disorder for which genetic material sets the stage; excessive sodium precipitates it and perpetuates it. Extra salt makes all forms more rapidly progressive and accelerates the onset of terminal events; extra potassium is everywhere protective. When an entire population eats excessively of salt, hypertension will develop among those genetically susceptible, but epidemiologic studies of salt versus blood pressure will not show a relation of salt to hypertension. This is the saturation effect. Low sodium diets are therapeutically effective but generally regarded as an impossible or an unnecessary nuisance. Effective prevention programs must be instituted at as early an age as possible. The efficacy of a prophylactic/therapeutic low sodium-high potassium diet should be weighed against the uncertain hazards of a lifetime of pill taking.

A metabolic control mechanism for calcium ion influx that may protect the ventricular myocardial cell

Abstract: Calcium ion influx into the myocardial cell during the action potential initiates and controls the degree of contraction. The Ca ++ influx leads to an increase of the myoplasmic free Ca ++ concentration to about 10 −5 molar for activation of the myofibrils; Ca ++ may also be released from the sarcoplasmic reticulum by the entering Ca ++ or by voltage change across its membrane. The inward Ca ++ current during the action potential plateau traverses the sarcolemma through a separate set of slow cation channels that have some peculiar properties compared to fast sodium ion channels: Slow channels are not sensitive to tetrodotoxin, have lower activation and inactivation potentials and are kinetically slow (slow activation, inactivation and recovery processes). Slow Ca ++ channels require metabolic energy and are blocked by verapamil, manganese ion, lanthanum ion and acidosis. When the fast Na ++ channels are blocked by tetrodotoxin or voltage inactivated by 27 millimolar potassium ion, excitability is lost but can be restored by catecholamines and methylxanthines: Propagating slowly rising electrical responses (accompanied by contractions) occur that resemble the plateau of the normal action potential. Positive inotropic agents such as norepinephrine, theophylline and histamine appear to act by elevating cyclic adenosine monophosphate (AMP) levels and increasing the number of Ca ++ channels available for voltage activation. Increased cyclic AMP could lead to phosphorylation of a membrane protein constituent of the slow channels by means of a cyclic AMP-dependent protein kinase and adenosine triphosphate (ATP). Thus, the myocardial cell exercises control over the number of available slow channels and, hence, the Ca ++ influx per impulse. This control mechanism could serve to protect the myocardial cell during periods of regional ischemia by acting to conserve ATP through reduced Ca ++ influx and contraction, and thus preventing the affected cells from working themselves to death. The Ca ++ channels in ischemic cells could be made inoperative by decreased ATP, decreased pH or accumulation of some other metabolite.

Congenitally corrected transposition of the great arteries: Morphologic study of 32 cases

Abstract: The detailed anatomy of the heart is described in 32 autopsy cases of congenitally corrected transposition of the great arteries.Tis condition is defined as the combination of atrioventricular (A-V) discordance and transposition of the great arteries. Examples of primitive (single) ventricle with "inverted" (that is, left-sided in situs solitus) outlet chamber are excluded. Six hearts with A-V discordance and pulmonary atresia are described in an appendix. In 29 cases of corrected transposition the heart was in situs solitus; in 3 it was in situs inversus totalis. Only 5 of these 32 hearts had no potential for intracardiac shunting. Anomalies of the tricuspid valve (91 percent of cases), ventricular septal defect (78 percent) and pulmonary outflow tract obstruction (44 percent) occurred with sufficient frequency to be considered part of the basic malformation and are described in detail. The precise anatomy and disposition of the A-V valve tension apparatus, the coronary arteries and the conducting tissues are described with special reference to possible surgical approaches for repair of the anomalies. In two hearts with situs solitus the aortic valve was right-sided with respect to the pulmonary valve. This finding is important for both diagnosis and nomenclature.

Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs

Abstract: Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.

Effects of electrical countershock on serum creatine phosphokinase (CPK) isoenzyme activity.

Abstract: Total and MB serum creatine phosphokinase (CPK) activity levels were measured serially in 30 patients treated with direct current electrical countershock, 17 patients with acute myocardial infarction and 25 normal subjects. In addition, serial determinations of total and MB CPK in serum were performed in 11 closed chest anesthetized dogs subjected to 10 repetitive countershocks at 15 second intervals with a delivered energy of 240 joules per countershock. Less than 4 milli-international units (mlU)/ml of MB CPK was found in the serum of normal subjects. Patients with myocardial infarction whose elevated total CPK levels were comparable with those of patients treated with cardioversion had a substantial rise in MB CPK activity, with peak values averaging 39 ± 6 mlU/ml (mean ± standard error). Fifteen of the 30 patients treated with countershock had elevated total CPK activity that peaked within 4 hours. In this group, MM CPK elevations accounted for the overall rise in CPK activity. In two patients, modest elevations of MB CPK (11 and 13 mlU/ml, respectively) were observed after cardioversion. In all 11 dogs total CPK increased after countershock, peaking to 1,888 ± 410 mlU/ml within 6 hours. Six dogs had increased MB CPK activity (52 ± 6 mlU/ml) and myocardial necrosis demonstrable histologically 4 days later. The results indicate that (1) myocardial damage in dogs produced by intense, repetitive countershock is associated with increased serum MB CPK; and (2) countershock as conventionally used in patients does not generally produce myocardial damage and serum MB CPK elevation. Although release of MB CPK into serum occasionally occurs after countershock, perhaps reflecting myocardial damage, the elevations appear to be modest. Thus, electrical countershock does not obscure the diagnosis of myocardial infarction or impair quantitative assessment of the extent of myocardial damage based on analysis of serum MB CPK activity.

Cardiac rhabdomyoma: A clinicopathologic and electron microscopic study

Abstract: Cardiac rhabdomyomas are rare tumors of infancy. In a series of 36 patients 78 percent were under 1 year of age, and only one patient was over age 15 years. Ninety percent of the rhabdomyomas were multiple and occurred with nearly equal frequency in the right and left ventricles. Although reportedly infrequent in the atria, rhabdomyomas involved either one or both atria in 30 percent of patients. In 50 percent of patients at least one of the tumor masses was intracavitary and obstructed 50 percent or more of one of the cardiac chambers or valve orifices. Symptoms referable to obstruction of intracardiac blood flow were present in nine patients, none of whom had tuberous sclerosis, and all of whom would appear to have been good surgical candidates. Histologically the rhabdomyomas were composed of classic "spider cells". Electron microscopic studies revealed scattered bundles of myofibrils ringing these cells and radiating toward the center; glycogen was present both free in the cytoplasm and within mitochondria. Distinct intercellular junctions resembling intercalated discs with well defined desmosomes and nexuses were present. Many of the cells contained leptofibrils, arranged either peripherally or in spiraled clusters in the center of the cell. Rhabdomyomas derive from cardiac muscle cells and appear to represent hamartomas rather than true tumors.

Discrete subvalvular aortic stenosis in childhood. Study of 51 patients.

Abstract: Fifty-one children with discrete subvalvular aortic stenosis were studied between 1951 and 1974. The three anatomic types of obstruction found were the thin membranous type (43 cases), the fibromuscular collar type (5 cases) and the tunnel type (3 cases). The obstruction was usually severe, and the median left ventricular to aortic systolic pressure gradient was 90 mm Hg. Progressive obstruction with an increasing gradient was documented in 10 patients by serial cardiac catherizations. Significant associated cardiac defects, present in 57 percent of patients, often masked the typical clinical and cardiac catheterization features of subaortic stenosis. The stenosis was often not discovered until after surgery for the associated defect. Forty patients underwent surgical resection of the discrete subaortic obstruction. After surgery significant left ventricular to aortic pressure gradients can be found at postoperative cardiac catheterization. These gradients may reflect inadequate resection of the more complex discrete obstructions or represent proliferation and regrowth of the previously resected subvalvular fibrous tissue. The criteria for operability of discrete subaortic stenosis should be the angiographic demonstration of a discrete subvalvular diaphragm and the presence of a resting left ventricular to aortic systolic pressure gradient of 40 mm Hg or more.

Vein graft patency and intimal proliferation after aortocoronary bypass: Early and long-term angiopathologic correlations

Abstract: To determine the clinical significance of intimal proliferation as a cause of aortocoronary bypass vein graft obstruction, 492 vein grafts from 281 patients were studied 0 to 75 months postoperatively. All grafts had been inserted between 1968 and 1975 by one surgeon using one technique. The graft patency rate was 92 percent (55 to 60) in the first month; 91 percent (49 of 54) at 1 to 3 months; 84 percent (37 to 44) at 4 to 6 months; 77 percent (33 of 43) at 7 to 12 months; 81 percent (113 of 140) at 13 to 24 months; 82 percent (59 of 72) at 25 to 36 months; and 84 percent (66 of 79) at 37 to 75 months. Vein graft samples were obtained from 41 patients: In 27 patients with 51 grafts (early group), they were obtained 0 to 30 days (mean 14 days) postoperatively; in 14 patients with 27 grafts (late group) they were obtained 7 to 75 months (mean 34 months) postoperatively. Intimal proliferation was graded 1 to 4 corresponding to an intima/media thickness ratio of 1,2,3 or 4, respectively. In the early group, all 51 vein grafts howed grade 1 to 2 intimal proliferation; 5 of these grafts were occluded, all as a result of recent thrombosis. In the late group, 17 of the 27 grafts were studied histologically. All patent vein grafts showed grade 2 to 3 intimal prolferation. Four vein grafts were occluded but only one as a result of grade 4 intimal proliferation. In 14 patients in the late group, angiograms performed shortly before vein graft samples were obtained revealed 14 patent and 4 occluded vein grafts. Ten of the 14 patent vein grafts showed grade 2 to 3 intimal proliferation but were of uniformly good caliber angiographically (graft/artery ratio more than 1.5).

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases

Abstract: A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome; 16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites. In contrast to findings in patients manifesting only typical exertional angina, the hemodynamic findings during spasm were those of a hypodynamic state. Left ventricular systolic pressure decreased from 138.9 ± 6.0 (mean ± standard error of the mean) to 113.2 ± 6.2 mm Hg; left ventricular end-diastolic pressure did not change significantly. Myocardial lactate extraction during spasm was invariably markedly reduced: −53.19 percent ± 15.44 ( P The respective roles of medical and surgical intervention are uncertain. Only 3 patients had a completely satisfactory pharmacologic response to nitrates alone or in combination with propranolol, and the condition of 5 others was partially improved; the remaining 21 patients were judged intractable to medical management. Coronary bypass surgery was performed as the ultimate recourse in 18 patients. However, short-term results reveal that only nine (50 percent) showed improvement, four (22 percent) had myocardial infarction during or after surgery and four (22 percent) died. These studies confirm that coronary arterial spasm is a definite pathogenetic factor in a variety of acute myocardial ischemic syndromes. The incidence and full clinical significance of this functional disorder remain to be determined.

Serial measurements of left ventricular ejection fraction by radionuclide angiography early and late after myocardial infarction.

Abstract: The left ventricular ejection fraction was determined serially with radioisotope angiography in 63 patients with acute myocardial infarction. After the peripheral injection of a bolus of technetium-99m, precordial radioactivity was recorded with a gamma scintillation camera and the ejection fraction calculated from the high frequency left ventricular time-activity curve. Since this technique requires no assumptions with respect to left ventricular geometry, it is particularly useful in patients with segmental left ventricular dysfunction. Serial measurements during the first 5 days after hospital admission were made in 50 patients, 30 of whom were studied during the subsequent 2 to 39 months (mean 19.9 months). Late follow-up serial studies were also performed in an additional 13 patients who had only one measurement of the left ventricular ejection fraction during the early postinfarction period. Early after infarction, the left ventricular ejection fraction was normal (more than 0.52) in only 15 of the 63 patients, and averaged 0.52 ± 0.05 (standard deviation) in the 27 patients with an uncomplicated infarct. The ejection fraction was reduced in 24 patients with mild to moderate left ventricular failure (0.40 ± 0.05, P < 0.0001) and in the 12 patients with overt pulmonary edema (0.33 ± 0.07, P < 0.0001). In 35 patients the ejection fraction correlated with the mean pulmonary arterial wedge pressure (r = 0.72). In 15 patients with normal left ventricular wall motion by heart motion videotracking, the ejection fraction was significantly higher (0.53 ± 0.08) than in the 26 patients with regional left ventricular dysfunction (0.41 ± 0.10, P < 0.0001). During the early postinfarction period, the left ventricular ejection fraction improved in 55 percent of patients and remained unchanged or decreased in 45 percent. A further increase in the ejection fraction was noted in 61 percent of patients during the late follow-up period. Patients with an initially low or decreasing ejection fraction had a significantly greater incidence of early mortality and left ventricular dysfunction (P < 0.02) than those whose ejection fraction was normal or improved to normal early after infarction. These data indicate that the ejection fraction is a sensitive indicator of left ventricular function after acute myocardial infarction and that serial measurements are helpful in predicting early mortality and morbidity.

Prosthetic valve endocarditis: Clinicopathologic analysis of 22 necropsy patients with comparison of observations in 74 necropsy patients with active infective endocarditis involving natural left-sided cardiac valves

Abstract: Clinical and morphologic features are described in 22 necropsy patients with endocarditis involving rigid-framed prosthetic valves: aortic in 15 patients and mitral in 7. The interval from valve replacement to onset of symptoms of prosthetic valve endocarditis was less than 2 months in 8 patients and longer than 2 months in 14 patients. The most frequent infecting organism was the Staphylococcus (13 patients). In each of the 22 patients the infection was located behind the site of attachment of the prosthesis to the valve ring, and the infection spread to adjacent structures in 13 patients, 11 of whom had aortic prostheses. Prosthetic detachment causing severe regurgitation occurred in 12 ot the 15 patients with an infected aortic valve prosthesis, and in 2 of the 7 with an infected mitral valve prosthesis. Prosthetic obstruction by vegetative material occurred in 5 of 7 patients with prosthetic mitral infection and in only 1 of 15 with prosthetic aortic infection. High degrees of conduction defects developed in seven patients with aortic prosthetic valve endocarditis: complete heart block in five, and complete left bundle branch block in two. Comparison of observations in the 22 patients with prosthetic valve endocarditis with those in 74 patients with active infective endocarditis involving natural left-sided cardiac valves revealed significant ( P

Coronary arterial reperfusion. III. Early and late effects on regional myocardial function and dimensions in conscious dogs

Abstract: Regional myocardial function was studied in five conscious chronically instrumented dogs for 4 weeks after coronary reperfusion following a 2 hour period of occlusion of the left circumflex coronary artery. A cuff and flowmeter were placed around the left circumflex coronary artery, and a micromanometer and three pairs of ultrasonic crystals were implanted 1 cm apart subendocardially in control, marginal and ischemic segments of the left ventricle. Control normal segments showed progressive increases in end-diastolic length and extent of active shortening. Ischemic segments tended to show slight improvement early after reperfusion, but in succeeding weeks, despite some improvement in shortening, they showed progressive decreases in end-diastolic length compatible with subendocardial tissue loss. In marginally ischemic segments, shortening initially remained depressed after reperfusion, but showed late recovery so that shortening and end-diastolic length were not different from control values by 4 weeks. These results contrasted with findings in five similarly studied dogs subjected to permanent coronary occlusion; in that group the data suggested greater tissue loss and less recovery of function in marginal and ischemic segments. The late return of segmental function and reduced loss of subendocardial tissue several weeks after coronary reperfusion suggest that substantial time periods may be required to assess the ultimate effect of therapeutic interventions. The findings further indicate that in this experimental model the usual time constraints for occurrence of irreversible tissue damage do not apply to all of the myocardium within the ischemic zone.

Influence of dobutamine on hemodynamics and coronary blood flow in patients with and without coronary artery disease

Abstract: The influence of dobutamine on hemodynamics and coronary blood flow was studied in patients after routine cardiac catheterization. The data demonstrated that dobutamine is a powerful inotropic agent at a dose that has a relatively small influence on heart rate. In patients without coronary artery disease dobutamine greatly increased coronary arterial perfusion. In patients with severe coronary artery diseases dobutamine resulted in a much smaller increase in coronary perfusion, and the pattern of perfusion became more inhomogeneous. The results suggest that dobutamine has a potential inotropic value but raise concern about its influence on regional myocardial perfusion in patients with serious coronary artery disease.

Propranolol-induced reduction of signs of ischemic injury during acute myocardial infarction.

Abstract: The effect of intravenous administration of propranolol (3 to 10 mg) was studied in 12 patients with acute anterior transmural myocardial infarction within the first 8 hours from the onset of pain. Criteria for inclusion in the study were persistence of ischemic pain, S-T segment elevation of 0.3 or more mv in at least two standard precordial leads, heart rate of 80 or more beats/min, mean arterial pressure of 75 or more mm Hg and cardiac index of 2.5 or more liters/min per m 2 . Within 30 minutes of administration of propranolol, the sum of S-T segment elevations from leads V 1 through V 6 (∑ST 6 ) and the average S-T segment elevation over the left precordium recorded from multiple unipolar leads ( ST ) decreased significantly by 40 and 39 percent, respectively. At the same time, there was a significant reduction in heart rate (from 100 ± 3 [standard error of the mean] to 79 ± 4 beats/min), mean arterial pressure (from 112 ± 6 to 95 ± 5 mm Hg) and cardiac output (from 6.1 ± 0.3 to 4.1 ± 0.3 liters/min). Pulmonary capillary wedge pressure remained unaltered. Four hours later the hemodynamic variables had returned to control level, but the beneficial effect on myocardial injury persisted. These electrocardiographic changes were accompanied by resolution of ischemic pain and cessation of ventricular arrhythmias. The effects of propranolol were more pronounced in patients with angiographically demonstrable flow to the affected area of myocardium. Thus, administration of propranolol in the early hours of myocardial infarction can significantly reduce the signs of myocardial ischemic injury without excessively depressing myocardial function.

Effect of amiodarone in the Wolff-Parkinson-White syndrome.

Abstract: The effect of amiodarone in the Wolff-Parkinson-White syndrome was studied with programmed electrical stimulation of the heart in 15 patients. All 15 patients had circus movement tachycardias; 7 also had atrial fibrillation. Programmed electrical stimulation was performed before and after 14 days of oral administration of amiodarone. The effective refractory period of the accessory pathway lengthened in an atrioventricular direction in all patients and in a ventriculoatrial direction in eight patients. The effective refractory period of the atrium and ventricle lengthened in 14 and 12 patients, respectively. After administration of amiodarone, circus movement tachycardia could no longer be initiated in five patients. The zone of tachycardia narrowed in four patients, did not change in two and increased in seven. The effect of amiodarone on initiation of circus movement tachycardia could be related to differences in effect of the drug and in the mechanism of tachycardia in individual patients. In all patients in whom tachycardias could still be initiated after treatment with amiodarone the heart rate during tachycardia was slower than before treatment. This slowing was caused by a decrease in conduction velocity of the circulatory wave in different parts of the tachycardia circuit. The effect of amiodarone in prolonging the refractory period of the accessory pathway makes this drug especially useful in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation.

Long-term evaluation of early repolarization syndrome (normal variant RS-T segment elevation).

Abstract: The electrocardiograms of 65 patients with the "early repolarization syndrome" (normal variant of RS-T elevation) were analyzed to delineate the features and evaluate the natural history of this electrocardiographic entity. Maximal follow-up was 26 years. The syndrome was characterized by (1) an upward concave elevation of the RS-T segment with distinct or "embryonic" J waves, slurred downstroke of R waves or distinct J points or both; (2) RS-T segment elevation commonly encountered in the precordial leads and more distinct in these leads; (3) rapid QRS transition in the precordial leads with counterclockwise rotation; and (4) persistence of these characteristics for many years although some intraindividual changes were common. Less commonly found were (5) tall R and T waves in the precordial leads; (6) "labile" or "juvenile" T wave patterns; (7) "pseudo-R" waves; and (8) "isolated T negativity syndrome." These changes commonly simulate pericarditis, myocardial ischemia, left ventricular hypertrophy and right bundle branch block.

Role of hypertension in atherosclerosis and cardiovascular disease.

Abstract: Clinical, experimental and pathologic studies strongly indicate that hypertension is a major factor in coronary heart disease, sudden death, stroke, congestive heart failure and renal insufficiency The deleterious effect of the elevated blood pressure on the cardiovascular system appears to be due mainly to the mechanical stress placed on the heart and blood vessels Humoral factors and vasoactive hormones such as angiotensin, catecholamines and prostaglandins may play a role in the pathogenesis of hypertensive cardiovascular disease but this role has not yet been defined and is probably secondary Hypertension, and the resulting increase in tangential tension on the myocardial and arterial walls, leads to the development of hypertensive heart disease and congestive heart failure as well as hypertensive vascular disease that affects not only the kidneys but also the heart and brain Hypertensive vascular disease involves both large and small arteries as well as arterioles and is characterized by fibromuscular thickening of the intima and media with luminal narrowing of the small arteries and arterioles The physical stress of hypertension on the arterial wall also results in the aggravation and acceleration of atherosclerosis, particularly of the coronary and cerebral vessels Moreover, hypertension appears to increase the susceptibility of the small and large arteries to atherosclerosis Thus the patient with hypertension is a candidate for both hypertensive and atherosclerotic vascular disease of the coronary and cerebral vessels leading to occlusive disease of both the large and small arteries and resulting in myocardial infarction and stroke Other major complications of hypertensive vascular disease include rupture and thrombotic occlusion of blood vessels, especially in the brain Disease of the arterial media, which begins in childhood with the deposition of calcium in the vessels, may be an important cause of arterial hypertension This form of hypertension may manifest itself in adults as arteriosclerotic hypertension and lead to cardiovascular complications very similar to those of essential hypertension The relation of arteriosclerotic hypertension to nutritional factors, including dietary salt intake, deserves study

Cardiac amyloidosis, constrictive pericarditis and restrictive cardiomyopathy

Abstract: Cardiac amyloidosis is not characterized by a single hemodynamic pattern. Some of the cases present the clinical findings of restrictive cardiomyopathy and in these differentiation from constrictive pericarditis remains difficult in spite of the introduction of techniques designed to assess myocardial contractility and ventricular diastolic compliance. The clinical features and the demonstration of left ventricular diastolic pressure greater than right remain the most useful means of distinguishing restrictive cardiomyopathy from constrictive pericarditis. In other cases of cardiac amyloidosis the diastolic pressure is elevated throughout diastole and ventricular ejectile ability is lost. These cases do not simulate constrictive pericarditis and should not be classified as restrictive cardiomyopathy.

Activation of left ventricular receptors with nonmedullated vagal afferent fibers during occlusion of a coronary artery in the cat.

Abstract: Studies were made of the effects of temporary occlusion of a coronary artery on the activity of nonmedullated afferent vagal fibers from the left ventricle of 15 cats. Recordings were made from 14 single fibers and 4 filaments with 2 to 3 fibers dissected from the right vagus. Their normal activity averaged 1.8 impulses/sec, and they were identified by an increase in activity to 4 to 17 impulses/sec during a brief occlusion of the aorta and by a conduction velocity of 0.6 to 1.3 m/sec (mean 0.9). The receptors studied were distributed throughout the ventricle, as determined by mechanical probing of the nonbeating heart at the end of the experiments. With a 1 to 1.5 minute occlusion of a coronary artery, the activity of receptors within the area supplied by that artery increased in concert with the systolic bulging of the Ischemic area. The initial increase in activity occurred during systole, suggesting that the receptors were activated mechanically rather than by chemical changes in the Ischemic zone. The activity soon became continuous, reaching a maximum of 15.4 impulses/sec (mean value). The maximal activity was not sustained; during occlusion of up to 40 minutes it decreased to 5 impulses/sec (mean value) after 5 to 10 minutes. The decrease may result from anoxia since three of four tested receptors showed an increase in activity after release of occlusion.

Functional significance of coronary collateral vessels in patients with acute myocardial infarction: Relation to pump performance, cardiogenic shock and survival

Abstract: In 20 patients with acute myocardial infarction requiring emergency left heart catheterization and coronary arteriography, ventricular function and clinical course were related to collateral vessels supplying the infarcted area. The major coronary artery to the infarcted region was severely obstructed in all patients. Patients with adequate collateral vessels (Group I, no. = 6) and those with no or inadequate collateral channels (Group II, no. = 14) had similar findings with respect to age, site of infarction, prevalence of prior infarction and presence of multivessel disease. However, there were significant differences between Groups I and II in left ventricular end-diastolic pressure (13 versus 30 mm Hg), cardiac index (3.05 versus 2.04 liters/min per m2), stroke work index (45 versus 13 g · m/m2), ejection fraction (42 versus 20 percent) and area of dyssynergy (14 versus 47 percent). Moreover, in Group I all patients survived and none had cardiogenic shock, whereas in Group II 10 of 14 patients had shock and 8 of 14 died. The rapidity of vessel obstruction appeared to influence collateralization since infarction was preceded by angina pectoris more frequently in Group I than in Group II. These results indicate that well functioning anastomotic channels to the distal trunk of the blocked coronary artery may afford some protection of pump function and improve the prognosis in acute myocardial infarction.