Unstable angina pectoris: a comparison of the costs of medical and surgical treatment.

This study compares the inpatient costs of therapy of patients with unstable angina pectoris randomized to surgical or medical therapy at the University of Alabama in Birmingham as part of the National Cooperative Study Group. For 74 patients followed up for 2 years, the mean inpatient charges were $4,728 for 22 medically treated patients, $9,528 for 34 surgically treated patients and $20,215 for 18 patients who crossed over from medical to surgical therapy. Differences among the three groups were statistically significant (P less than 0.001). Stepwise multiple regression analysis of total inpatient charges with medical and procedural factors as explanatory variables showed that a history of congestive heart failure, the number of infarctions during the period of the study, the duration of the longest anginal attack, the type of unstable angina and the type of treatment were significant predictors of total inpatient cost, with an R2 value of 0.829 (P less than 0.001). These variables explain the cost of treatment. One should not infer that they will also predict the appropriate type of treatment for patients with unstable angina. Although the cost of surgical therapy was double the cost of therapy for patients treated only medically, those medically treated patients whose therapy failed and who subsequently required surgery incurred mean costs twice those of the surgically treated patients and four times of patients who received only medical therapy. Reassessment of previous criticism of the high cost of surgical therapy is indicated.     

Displacement of the heart by a giant mediastinal cyst.

A giant mediastinal cyst caused marked cardiac displacement, factitious cardiomegaly and clinical and hemodynamic findings suggestive of constrictive pericarditis. The correct diagnosis was established with echocardiography and confirmed with angiography and surgery.     

Surgical versus medical therapy for treatment of unstable angina: Changes in work status and family income

Employment and income status of 96 patients randomized into the Alabama portion of the National Cooperative Unstable Angina Study were evaluated before the patients' admission to the study and in 1977. All patients had at least 12 months of follow-up study (mean 38 months). The ratio of patients fully employed at the time of follow-up to those fully employed at entry into the study (baseline) was 0.68 for medically treated patients, 0.53 for surgically treated patients and 0.53 for patients in whom medical therapy failed and who later underwent operation. The changes in annual family income were +$1,111 for medical patients, ?$2,447 for surgical and +$875 for those later undergoing surgery. Regression analysis revealed that nonwork income, initial work status, initial income, severity of angina while the patient was in the unstable angina study and the procedural variable (that is, persistent medical, early surgical or late surgical treatment) were associated with return to full-time employment. Changes in family income were related to change in work status, the procedural variable, the patient's education, initial work status, the spouse's income, occurrence of a myocardial infarction after entry into the unstable angina study, duration of angina before entry into the unstable angina study, marital status and sex. Patients who underwent initial surgery had the largest reduction in family income, related to the change in nonworking status at the time of follow-up interview.     

Fine structure of cells and their histologic organization within internodal pathways of the heart: clinical and electrocardiographic implications.

The fine structure of the normal internodal pathways was studied in 1 human and 2 canine hearts and correlated with histologic observations on more than 100 human and 10 canine hearts. From the electron microscopic studies six different kinds of myocardial cells were classified from two locations: the Eustachian ridge (posterior internodal pathway) and the Bachmann bundle (anterior internodal pathway). Five of the six kinds of cells (working myocardial cells, Purkinje-like cells, either broad or slender transitional cells and P cells, all previously described) were present in both locations. A sixth cell, pleomorphic and dark in appearance, with a special intertwined relation to P cells, is newly designated as an ameboid cell. It was found solely in the Eustachian ridge. In the same area a rare direct contact between a nerve and a myocardial cell was observed. The importance of these different kinds of cells, their respective cell connections, and their topographic locations inside the internodal pathways are discussed relative to certain functions such as rapid conduction and subsidiary pacemaking. The possible influence of these factors on clinical electrocardiographic changes is considered.     

Reflex heart block: Baroreflex, chemoreflex and bronchopulmonary reflex causes

Reflex heart block was studied in 20 dogs anesthetized with sodium pentobarbital and in 5 trained unanesthetized dogs. Three different vagal reflexes were produced: the Marey response during hypertension caused by administering methoxamine, a cardiogenic hypertensive chemoreflex activated by injection of serotonin into the left atrium and the Hering-Breuer reflex observed during normal respiration of unanesthetized dogs. In every dog during any of the three reflexes heart block was consistently observed after the normal slowing response of the sinus node had been selectively eliminated by the direct perfusion of 10 μg of atropine into the sinus node artery. This was a uniform response despite its being variously produced by a pressor reflex, a chemoreflex or an extracardiac bron-chopulmonary reflex. Transient heart block is therefore to be anticipated during reflexes with vagal efferent components if for any reason the sinus node is incapable of slowing suitably. The possible clinical relevance of these experimental observations is discussed.     

Elevated catecholamines during cardiac surgery: consequences of reperfusion of the postarrested heart

This study determines whether reperfusion of the heart with elevated blood levels of epinephrine (E) and norepinephrine (NE) during cardiac surgery produces deleterious effects. The study was conducted in 60 patients undergoing coronary artery bypass surgery. Arterial catecholamine values increased significantly (p less than 0.05), from prebypass control levels of 152 +/- 29 and 327 +/- 30 pg/ml of E and NE, respectively, to 415 +/- 78 and 554 +/- 49 pg/ml, at initiation of perfusion of the heart after the aortic cross-clamp was removed. Serial measurement of arterial (A) and coronary sinus (CS) E, NE, potassium, lactate, PO2 and CK-MB revealed that during 10 minutes of reperfusion the heart extracted E (positive A-CS difference, p less than 0.05), but that the NE A-CS difference was 0. The CS effluent contained significantly (p less than 0.05) higher concentrations of potassium, lactate and CK-MB during reperfusion than before aortic occlusion. There was no significant correlation of arterial E and NE, CS E and NE or A-CS differences in E and NE with myocardial release of lactate, potassium or CK-MB. There was a weak association (r = 0.4, p less than 0.01) between coronary sinus CK-MB and aortic occlusion time. Maximal arterial E and NE values did not correlate with 10-hour postoperative (maximal) CK-MB values. These results indicate that reperfusion of the postarrested ischemic heart with high levels of endogenously released catecholamines does not worsen ischemia or contribute significantly to myocardial damage.     

Attenuation by magnesium of the electrophysiologic effects of hyperkalemia on human and canine heart cells

Because magnesium (Mg⁺⁺) has been shown to promote maintenance of a negative resting potential it might oppose the depolarizing effect of potassium (K⁺) in cardiac cells. To test this hypothesis the electrocar diographic changes that occur during hyperkalemia were prospectively studied in 11 patients, 4 of whom had hypermagnesemia. Action potential studies were carried out in single atrial and ventricular cells isolated from 11 canine hearts using similar extracellular concentrations of Mg⁺⁺ _° and K⁺ _° to elucidate further the relative effects of these cations. Hyperkalemia was associated with a marked reduction in P wave amplitude and marked prolongation of the QRS complex. However, normal P waves and normal QRS durations were recorded in hyperkalemic patients with excess Mg⁺⁺ (2.5 mEq/liter or more). Mg⁺⁺ also antagonized some effects of K⁺ in the isolated atrial and ventricular tissues. With elevated levels of [Mg⁺⁺] the K⁺-induced depolarization of the resting potential was less than half as much as when [Mg⁺⁺]was normal (9 versus 21 mV in ventricular cells and 18 versus 40 mV in atrial cells). Furthermore, the fall in linear conduction velocity that accompanied elevated [K⁺]levels in ventricular cells failed to occur when the level of [Mg⁺⁺]was high. Mg⁺⁺-K⁺ antagonism helps to explain the preservation of a normal P wave because the onset of K⁺ effects in isolated atrial cells was delayed when [Mg⁺⁺]was high and action potential amplitude was improved. It is concluded that the heart cells of patients with high serum levels of [Mg⁺⁺]were less sensitive to an increase in [K⁺]than were those of patients with lower [Mg⁺⁺]and, accordingly, that Mg⁺⁺ attenuated the electrophysiologic response to elevated [K⁺].     

Intracardiac surgery in infants under age 3 months: Predictors of postoperative in-hospital cardiac death

Data are reported on 142 infants less than 3 months old who left the operating room alive after an open intracardiac operation during the 13 years from January 1967 to July 1980. The probability of postoperative in-hospital cardiac death for acute postoperative heart failure (the most common mode of death in these infants) was found by multivariate logistic analysis to be significantly related only to the strength of pedal pulses, the pedal skin temperature and the cardiac index in the first 5 postoperative hours. When cardiac index was not analyzed and cold cardioplegic myocardial preservation methods used, only pedal pulses and pedal skin temperature were significant predictors of hospital death. Blood pressure and heart rate were not related to this mode of hospital death. Oliguria occurred in 23 percent of patients; it was related primarily to inadequate cardiac performance and increased the probability of hospital death. Treatment protocols are derived based on these facts.     

Experimental studies on the pathogenesis of asystole after verapamil in the dog.

The effect of verapamil on automaticity and conduction in the atrioventricular (A-V) junctional region was studied in anesthetized dogs. In five normal dogs verapamil, 10 microgram/ml, was selectively perfused into the A-V nodal artery and caused first degree heart block, which progressed to second degree heart block in three of the five. Higher concentrations of verapamil, 25 microgram/ml, caused complete heart block in three of five other dogs, but no episodes of asystole (defined as a ventricular pause of 10 or more seconds). In six other dogs after beta receptor blockade with propranolol, 20 microgram/ml, perfused into the A-V nodal artery, verapamil, 10 microgram/ml, regularly caused second degree heart block; in four of the six dogs there was a transient episode of third degree A-V block, and in two of these there was a period of asystole. In each of the 10 dogs pretreated with reserpine, verapamil, 10 microgram/ml, caused third degree A-V block; in seven of these there was a period of asystole with ventricular standstill up to 30 seconds. Concentrations of verapamil that do not produce high grade heart block in the normal heart thus readily cause both high grade block and prolonged ventricular standstill after elimination of adrenergic influences in the A-V junction.     

Coronary anatomy and arteriography in patients with unstable angina pectoris.

A prospective series of 188 patients with the syndrome of unstable angina pectoris undergoing coronary arteriography was reviewed to determine the spectrum of anatomic coronary artery disease, suitability for coronary revascularization and in-hospital morbidity and mortality. Thirty-two patients demonstrated normal to moderately diseased coronary arteries. None of these patients sustained myocardial infarction or died. Twenty patients (10.6 percent) had normal coronary arteriograms. Of the 156 patients having severe coronary artery disease (greater than 70 percent stenosis), 20 patients (13 percent) had left main coronary artery disease. One hundred forty-two patients (91 percent) were potential candidates for coronary surgery; 14 were not candidates because of distal vessel disease or poor left ventricular function. During cardiac angiography or in the subsequent hospital period 12 patients sustained a myocardial infarction and 7 of these died. Of these seven, six had left main coronary artery disease and one had three vessel disease. In three patients who died (1.9 percent of those with severe coronary artery disease) the death may have been related to cardiac catheterization because evidence of myocardial necrosis began within 24 hours of study. Thus, patients with the syndrome of unstable angina pectoris usually presented with severe coronary artery disease and were candidates for coronary revascularization. The anatomic severity of coronary artery disease appeared to be the most important factor contributing to myocardlal infarction or death after cardiac catheterization. Mortality after catheterization was primarily associated with left main coronary artery disease.     

Anatomic and physiologic considerations of a cardiogenic hypertensive chemoreflex.

Within both human and canine hearts there is a mass of chemoreceptor tissue lying just between the origins of the aorta and pulmonary artery and receiving its blood supply from the proximal portion of the left coronary artery. In the dog this is considered to be the site of origin for a powerful hypertensive reflex stimulated by serotonin. There is brief generalized arterial vasoconstriction, except for the coronary and pulmonary arteries. The afferent limb of this cardiogenic hypertensive Chemoreflex courses in thoracic branches of the vagus. Autonomic efferent responses are both vagal arid, sympathetic events. These include simultaneous positive and negative inotropic effects on the atria, a positive inotropic effect on both ventricles, positive and negative chronotropic actions and similarly mixed dromotropic effects. Methods for separately identifying and quantifying these responses are discussed and illustrated. Vagotomy eliminates the reflex, as does the administration of cyproheptadine (but not methysergide). Among possible human counterparts for this cardiogenic hypertensive Chemoreflex are the pressor responses associated with angina pectoris, with very early acute myocardial infarction and after certain forms of cardiac surgery such as saphenous vein bypass grafting.     

Intracardiac surgery in infants under age 3 months: Incremental risk factors for hospital mortality

During the 13 year period from January 1967 to July 1980, the hospital mortality rate for open intracardiac operations in infants in the first 3 months of life was 43 percent (75 deaths among 194 patients), higher than the 22 percent mortality rate (35 deaths in 161 patients) for closed operations in the same age group. The mortality rate was lower late in the experience (p = 0.0001). Poor preoperative condition of the patient increased the mortality rate 87 percent in patients preoperatively acidotic or in shock [preoperative class V]and 22 percent in patients with moderate or severe symptoms but without recent hemodynamic deterioration (preoperative class II or III). The presence of major associated cardiac lesions increased hospital mortality (p < 0.0001). The hospital mortality rate was highest (59 per cent) in infants less than age 1 month, possibly in part because of their sensitivity to the damaging effects of cardiopulmonary bypass. This hypothesis is supported by the association of a long period of cardiopulmonary bypass with increased hospital mortality (p = 0.05) and of total circulatory arrest during profound hypothermia with decreased mortality (p = 0.05). Most deaths (72 percent) occurred in association with acute postoperative cardiac failure. The length of cardiac ischemia (aortic cross-clamping time) was directly related to the probability of cardiac death, unless cold cardioplegia was used. Thirteen percent of the hospital deaths were associated with acute postoperative respiratory failure. Current mortality rates in typical cases without acute hemodynamic deterioration is estimated from these data to be 7 percent (70 percent confidence limits 4 to 12 percent), as a result of the scientific advances made over this period of time. Research into mechanisms of the damaging effects of cardiopulmonary bypass should further improve results in these very young patients.     

Left ventricular outflow tract obstruction in transposition of the great arteries: an angiographic study of 74 cases.

Recent advances in techniques of angiocardiography now allow highly accurate assessment of the anatomy of the left ventricle in patients with transposition of the great arteries. The cineangiograms of 225 children with transposition were reviewed using axial cineangiographic techniques and 33 percent were found to have significant left ventricular outflow tract obstruction with or without coexisting ventricular septal defects. The varieties of left ventricular outflow tract obstruction and the associated ventricular septal defects found in this group of patients are described, illustrated and correlated. The advantages of axial angiocardiography in the diagnosis of transposition are pointed out, and the techniques used to produce the axial angiocardiograms are reviewed.     

Isosorbide dinitrate for the relief of severe heart failure after myocardial infarction.

Severe congestive heart failure secondary to myocardial infarction remains a difficult management problem. Although intravenous vasodilators and mechanical assist devices have been reported to improve the depressed hemodynamic function, these interventions are limited to the intensive care unit and cannot be used for long-term management. This study evaluates the hemodynamic and symptomatic response to sublingual administration to isosorbide dinitrate (5 to 10 mg) in seven consecutive patients with severe congestive heart failure after anterior wall myocardial infarction. Serial measurements of mean right atrial and pulmonary arterial end-diastolic pressure, mean blood pressure, heart rate and cardiac output were obtained during the control period and during the 4 hours after administration of isosorbide dinitrate. The peak response occurred approximately 30 minutes after drug administration with an 83 percent reduction in mean right atrial pressure (from 6 to 1 mm Hg, P less than 0.02), a 36 percent reduction in pulmonary arterial end-diastolic pressure (from 25 to 16 mm Hg, P less than 0.0001) and a 6 percent reduction in mean blood pressure (from 94 to 88 mm Hg (P less than 0.05). There were small but statistically not significant increases in cardiac index (from 2.3 to 2.6 liters/min per m2 and stroke work index (from 26 to 32 gm/beat per m2). The total systemic vascular resistance was reduced by 5 percent from 1,605 to 1,518 dynes sec cm-5 (P less than 0.10). The baseline heart rate of 105 beats/min was not significantly changed. The reduction in pulmonary arterial end-diastolic pressure became statistically significant (P less than 0.05) between 15 and 30 minutes after administration of isosorbide dinitrate and remained significant for 3 to 4 hours. This reduction of pulmonary arterial end-diastolic pressure to less than 22 mm Hg was associated with relief of the patients' pulmonary symptoms. The response to nitroglycerin (0.4 mg) was similar in magnitude but of much shorter duration (approximately 15 minutes for nitroglycerin versus 4 hours for isosorbide dinitrate in patients with and without congestive heart failure. The slope (calculated by dividing the change in cardiac index or stroke work index by the change in pulmonary arterial end-diastolic pressure) was significantly (P less than 0.05) depressed in the patients with congestive heart failure. These data demonstrate that the symptomatic pulmonary venous hypertension can be effectively relieved by isosorbide dinitrate without further compromising left ventricular function.     

Sudden death while driving: Role of sinus perinodal degeneration and cardiac neural degeneration and ganglionitis

A young business executive was seen to slump over his steering wheel while driving, after which the automobile veered and turned over. Quickly taken unconscious to a nearby emergency room, he was pronounced dead on arrival. Because there was insufficient physical injury found to account for his death, and because atrial fibrillation had been detected for the first time on a routine physical examination 3 months previously, special examination of the cardiac conduction system was performed. A fibroma was present on the right side of the central fibrous body above the His bundle, similar to several fibromas on the mitral valve. Small foci of neuritis were present in the ventricular myocardium and the atrioventricular node. More extensive neural degeneration and ganglionitis were found near the sinus node, which also exhibited an encircling perinodal flbrosis. Ways in which these abnormalities could have caused a fatal electrical instability of the heart are discussed. Careful examination of the cardiac conduction system is warranted in other fatal automobile accidents under similar circumstances.     

Total occlusion of the left main coronary artery: The Coronary Artery Surgery Study (CASS) experience

Total occlusion of the left main coronary artery was confirmed on review of the coronary angiograms in 12 (0.06 percent) of the 20,197 patients entered into the Coronary Artery Surgery Study (CASS) before coronary arterial surgery. Clinical features alone could not distinguish the patients with total occlusion of the left main coronary artery from those enrolled in the CASS with subtotal stenosis of this vessel. The right coronary artery had a stenosis greater than or equal to 70 percent of luminal diameter in 7 of the 12 patients. Collateral flow to the left coronary artery was defined as “substantial” or “limited” based on the presence or absence of clear visualization of the main channel of either the left anterior descending or left circumflex coronary artery during coronary angiography. Of the eight patients with “substantial” collateral flow, one (13 percent) had an aneurysmal or dyskinetic left ventricular wall segment, whereas all (100 percent) of the three patients with “limited” collateral flow had dyskinesia or an aneurysm (p < 0.05). Seven patients underwent coronary bypass graft surgery; 6 (86 percent) of these patients were living at their most recent follow-up, a mean of 46 months after entry into the CASS. Two of these patients continued to have angina pectoris. Five patients did not undergo coronary bypass grafting and 2 (40 percent) were still alive at their most recent follow-up, a mean of 45 months after entry into the CASS. One of these patients had angina pectoris. The difference in survival between the medical and surgical groups was not statistically significant.

This study indicates that patients with total occlusion of the left main coronary artery are uncommon and cannot be distinguished by presenting features alone from patients having subtotal stenosis of the left main coronary artery. “Substantial” coronary collateral blood flow is associated with better left ventricular wall motion than is “limited” collateral flow. Prolonged survival and lessening of symptoms may occur after coronary bypass grafting although long-term survival is possible without it.