Medical versus surgical treatment of unstable angina

Unstable angina is an important symptom of coronary artery disease. Two general clinical presentations may occur: (1) stable angina with a recent increase in severity or angina of recent onset, or (2) acute coronary insufficiency or angina at rest with chest pain resembling that of acute infarction. The risk of death or infarction is greater in patients who have recurrent chest pain and ST-T wave abnormalities despite hospital treatment. In patients without electrocardiographic or serum enzyme evidence of a completed infarct, coronary arteriography and bypass graft surgery can be performed with an acceptably low mortality rate. Surgical treatment provides better symptomatic relief than medical management in many patients, but the significant incidence of perioperative infarction makes it difficult to determine if surgery prevents infarction. Some studies indicate that surgery improves survival in subgroups, but data from large scale randomized studies will be needed to answer this question securely. Patients with disease of the left main coronary artery should probably have surgical treatment.Medical treatment will relieve symptoms in most patients with unstable angina and on a long-term basis may obviate the need for surgery. A preliminary period of intensive medical treatment before surgery may be advantageous since there is little evidence that survival rates are improved by treating unstable angina as an acute surgical emergency.     

Unstable angina: comparison of medical and surgical management.

Medical versus surgical treatment of unstable angina was compared in a prospective nonrandomized study of 118 patients. Acute transient ST-T wave changes were present during chest pain in all patients. Acute infarction was excluded by serial electrocardiograms and enzyme studies. All patients admitted to the coronary care unit from 1970 to 1975 who fulfilled the entry criteria were included in the study. The starting point for data evaluation was 5 days after hospital admission. Characteristics at entry were similar in 66 medically treated patients and 52 patients who had coronary bypass vein graft surgery. During a mean follow-up period of 23 months in 66 medically treated patients with unstable angina the incidence rate of nonfatal myocardial infarction was 17% and the total mortality rate 21 percent compared with respective rates of 19% and 5.8% in 52 surgically treated patients. In the surgical group 8 patients (15%) had a perioperative infarction and only 2 (4%) had a late infarction; one patient (2%) died at operation. Symptomatic improvement was observed more frequently in the surgically treated group. Sixty percent of surgically treated patients were free of angina compared with 21% of medically treated patients. Eight medically treated patients (12%) required late surgical treatment for persistent severe angina despite optimal medical management.     

Effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias. Long-term follow-up of a prospective randomized study.

The effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias and their relation to sudden death was examined in 102 patients with stable angina pectoris randomly assigned to medical and surgical therapy (54 and 48 patients, respectively). Symptom-limited treadmill tests were performed at entry and at 1 and 5 years. The surgical group demonstrated significant improvement in exercise performance at 1 year compared with the medical group, and at 5 years exercise-induced ischemia as evidenced by S-T depression and exertional angina remained substantially decreased in the surgical group with little change in the medical group. However, the frequency and severity of exercise-induced ventricular arrhythmias in each group remained unchanged at 1 and 5 years from those at entry. Similar results were obtained from an evaluation of ventricular arrhythmias in the electrocardiogram at rest. With the exception of exercise-induced ventricular tachycardia and fibrillation, no relation was found between ventricular arrhythmias and sudden death. Coronary bypass grafting does not decrease the frequency or severity of exercise-induced or resting ventricular arrhythmias. In patients with stable angina pectoris, with the exception of ventricular tachycardia and fibrillation, exercise-induced ventricular arrhythmias are poor predictors of sudden death. The data suggest that exercise-induced ventricular arrhythmias may not be related to ischemia but to other effects of exercise such as cardiac stimulation by catecholamines or other factors.     

Relation of severity of symptoms to prognosis in stable angina pectoris

To determine if severity of angina is related to the extent of coronary artery disease (CAD) or prognosis, 341 patients were evaluated by a systematic physician-administered angina questionnaire at entry into a large-scale randomized study of medical vs surgical treatment of stable angina pectoris. Severity of angina was numerically scored; scores were based on frequency of pain, rest pain, amount of daily medication, and level of daily activity. Severity scores were separated into mild, moderate and severe groups of approximately equal numbers and correlated with (1) number of coronary arteries narrowed, (2) presence of left main CAD, (3) ejection fraction less than 50%, (4) abnormalities of left ventricular function, (5) 3-vessel CAD with abnormal left ventricular function, (6) increased heart size by chest x-ray, (7) a noninvasive measure of prognosis, and (8) mortality. Severity of angina was not significantly related to any of the above variables except for the presence of left main CAD (p = 0.046) and increased heart size by chest x-ray (p = 0.001), both of which had low prevalence rates. Severity of angina at baseline was not related to 7-year survival in patients treated medically or surgically. Severity of angina at baseline, however, did predict 1- to 2-year survival in medically treated patients. Similarly, the severity of angina at 1 year and severity at 5 years predicted survival in the subsequent 4 years in the medical group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left bundle branch block and mechanical events of the cardiac cycle

Left bundle branch block (LBBB) is associated with a prolongation of the interval from the QRS onset to the onset of left ventricular (LV) ejection. The locus and prevalence of specific sites of delay were examined in 56 patients with complete LBBB using echocardiography, phonocardiography and external pulse recordings. The results were compared with those in 52 control subjects without LBBB. The onset of the QRS complex was used as the initial reference point of measurement of time intervals. The following abnormalities were found in patients with LBBB: (1) delayed mitral valve closure (Q-MC greater than 0.08 second) was the major site of delay in 23% of patients; (2) prolongation of the LV isovolumetric contraction time (greater than 0.06 second) was the major site of delay in 41%; (3) both Q-MC and LV isovolumetric contraction time were prolonged in 18%; and (4) in 26% of patients the onset of ventricular contraction determined by the onset of the increase of the apex impulse was delayed (Q-VC greater than 0.07 second). The most common cause of delayed ejection was a prolonged LV isovolumetric contraction time, which occurred in 59% of patients. A control group of 20 patients with abnormal LV function but without LBBB had a low incidence of the 3 types of delay in LV ejection (0 to 15%). Thus, the major abnormalities in the cardiac cycle in LBBB are due to the conduction defect and not to LV dysfunction. The results of this study suggest the presence of variable abnormalities of conduction in complete LBBB.     

Patients with congestive cardiomyopathy as cardiac transplant recipients: Indications for and results of cardiac transplantation and comparison with patients with coronary artery disease

In recent years end-stage congestive cardiomyopathy has become an increasingly frequent clinical diagnosis in candidates for cardiac transplantation. Forty-six patients who underwent transplantation because of congestive cardiomyopathy and 59 because of coronary artery disease were studied between 1971 and 1978 at Stanford University. The overall 1 year survival rate was similar in the two groups: cardiomyopathy-transplant, 64 percent and coronary artery disease-transplant, 55 percent. The survival rate has improved substantially for both groups within the last decade: The 3 year survival rate for cardiomyopathy-transplant patients undergoing cardiac transplantation since 1974 is nearly 60 percent. In contrast, 36 similarly ill patients with cardiomyopathy not undergoing transplantation had a 1 year survival rate of 23 percent and a 3 year survival rate of 4 percent (p <0.001). Survival rates in the cardlomyopathy-transplant group were unaffected by age (greater or less than 40 years). Patients in this group under age 40 had a lower frequency of infection (1 per 313 patient-days versus 1 per 195 patient-days in the older group, p <0.05) and a significantly longer interval to second rejection episodes (p <0.05), a measure of rejection frequency. Cardiomyopathy-transplant patients under age 40 had fewer deaths due to rejection (17 percent) compared with older patients in this group (36 percent). Cardiac transplantation is an effective treatment for end-stage congestive cardiomyopathy.     

Cardiac arrest due to oral potassium administration

Cardiac arrest developed in two patients after the administration of oral potassium. Neither patient had renal insufficiency, but both had underlying heart disease. In one patient fatal ventricular fibrillation developed 4 days after he received an aortic valve replacement for aortic stenosis and while he was receiving oral potassium supplements. The serum potassium level before cardiac arrest was 8.1 meq. The second patient had angina and was given 40 meq of potassium orally 15 minutes after an exercise test which produced chest pain and S-T segment depression. One hour later, ventricular fibrillation developed. Resuscitation was successful. Both patients had electrocardiographic evidence of hyperkalemia. Oral administration of potassium may produce severe cardiac toxicity in patients with heart disease even when renal function is clinically normal.     

Effects of coronary artery bypass grafting on resting and exercise hemodynamics in patients with stable angina pectoris: a prospective, randomized study.

In this prospective randomized study, resting and exercise hemodynamics were determined in the nonmedicated state before ("entry") and 1 year after coronary bypass surgery in 38 patients, and at entry and 1 year in 40 patients treated medically. The surgical group showed a significant decrease in mean pulmonary arterial wedge pressure during exercise (entry 23.5 +/- 6.1 [standard error of the mean] mm Hg, 1 year 18.9 +/- 1.0, P less than 0.02); an increase in cardiac index during exercise (entry 4.3 +/- 0.1 liter/min per m2, 1 year 4.6 +/- 0.1, P less than 0.05); an increase in resting mean arterial pressure (entry 94.5 +/- 2.2 mm Hg, 1 year 100.2 +/- 2.2, P less than 0.02); and an increase in resting heart rate (entry 68.5 +/- 1.9 beats/min, 1 year: 76.0 +/- 2.0, P less than 0.01). Maximal treadmill exercise performance also improved significantly in the surgical group of patients (entry 285 +/- 24 seconds, 1 year 382 +/- 24, P less than 0.002). There were no significant changes in these variables in the medically treated "control" group. The improvement in pulmonary arterial wedge pressure during exercise and in maximal treadmill exercise time in the surgical group as a whole was due to striking improvement in these variables in a subgroup of 16 surgical patients who had a more than 10 mm Hg increase in pulmonary arterial wedge pressure during exercise in their entry study. In this subgoup, considered to contain those patients with marked "ischemicdysfunction," pulmonary arterial wedge pressure during exercise fell from 31.4 +/- 1.5 mm Hg (entry) to 19.l +/- 1.8 (1 year) (P less than 0.0001) and treadmill time increased from 217 +/- 24 seconds (entry) to 357 +/- 37 (1 year) (P less than 0.001). Thus, hemodynamic evidence of ischemic left ventricular dysfunction during stress may identify those patients who will show objective improvement in ventricular performance after bypass graft surgery.     

Traumatic pulmonary artery--left atrial fistula: an unusual case of cyanosis in an adult.

Eighteen months after sustaining a stab wound to the left upper chest, a 59-year-old man presented with cyanosis and extertional dyspnea. Arterial desaturation due to a central 22 per cent right-to-left shunt was present. A selective pulmonary arteriogram demonstrated a fistula between the main pulmonary artery and the left atrium. At operation the fistula was closed. A laceration of the pulmonic valve and healed pericarditis were present. Marked symptomatic improvement followed the operation, but a murmur of pulmonic valvular regurgitation persisted. The fistula and laceration of the pulmonic valve were probably traumatic in origin.     

The effect of coronary bypass surgery on exercise-induced ventricular arrhythmias.

Ninety-one patients with angiographically proved coronary artery disease and stable angina were randomly assigned into surgical and medical therapy. Graded exercise tests were performed on entry into the study and repeated in 1 year. Ventricular arrhythmias during exercise and 8 minutes of recovery were studied. Arrhythmias were graded on a scale of 0 to 7 by their presumed severity. On entry, both groups were similar in the severity of coronary disease, exercise capacity, and frequency and severity of exercise-induced ventricular arrhythmias. At 1 year, the frequency and severity of arrhythmias remained unchanged in both groups, whereas the surgically treated patients showed a marked improvement in their exercise capacity (p less than 0.005). The medically treated patients had a slight deterioration in their work capacity which, however, did not achieve statistical significance (p = 0.08). Twelve patients died suddenly. In seven medically treated patients who died suddenly, the frequency and severity of ventricular arrythmias on exercise were not different from those of the rest of the medical patients. In the five surgically treated patients who died suddenly, one had multiform premature ventricular beats, a second developed ventricular fibrillation (2 years before dying suddenly), and a third had no arrhythmias during exercise. Two died before the 1 year evaluation. Successful coronary surgery improves exercise capacity without decreasing associated ventricular arrhythmias. Exercise-induced ventricular arrhythmias, with the exception of ventricular fibrillation, may not be closely associated with the risk of sudden death.     

Acute myocardial infarction and ischemic injury during surgery for coronary artery disease.

The incidence of myocardial infarction, acute ischemic injury, and associated serum enzyme abnormalities has been evaluated in four operations involving the coronary circulation. The highest incidence of infarction was associated with internal mammary implantation (Vineberg procedure). There was no significant difference in the incidence of infarction, ischemic injury, or abnormal enzyme levels between patients with stable angina and those with unstable angina who had vein bypass surgery. In operations involving combined vein bypass grafting and valve replacement surgery, the incidence of abnormal serum enzyme elevations was higher than in any other procedure. The incidence of infarction and acute ischemic injury in combined operations was similar to that in other procedures but this may have been due to the difficulty in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs.     

Ability of exercise to inhibit carbohydrate-induced hypertriglyceridemia in rats

The ability of spontaneous running to prevent carbohydrate-induced hypertriglyceridemia was studied in young, nonobese rats. Exercise-trained and sedentary rats were fed a diet consisting of (as percent total calories) 12% fat, 22% protein, and 66% carbohydrate. The source of the carbohydrate was varied, and experiments were carried out with sucrose and glucose as the sole dietary carbohydrate. Plasma triglyceride (TG) levels rose in response to both forms of dietary carbohydrate in both sedentary and exercise-trained rats, but the magnitude of the elevation was greatly attenuated in the exercise-trained group. Plasma insulin concentrations were also significantly lower in exercise-trained rats. Measurements of hepatic very low density lipoprotein (VLDL)-TG secretion rate and adipose tissue lipoprotein lipase (LPL) activity were made in an effort to determine how exercise-training prevented the development of carbohydrate-induced hypertriglyceridemia. The results of these studies indicated that perfused livers of exercise-trained rats secreted significantly less VLDL-TG, whereas adipose tissue LPL activity of the two groups was similar. On the basis of these results, it is postulated that the ability of exercise-training to inhibit carbohydrate-induced hypertriglyceridemia is due to an increase in insulin sensitivity resulting from chronic exercise. As a result, the postprandial insulin responses to high carbohydrate diets would be relatively reduced in exercise-trained rats, leading to decreased hepatic VLDL-TG secretion, and lower plasma triglyceride concentrations.     

Functional homogeneity of pancreatic islets of aging rats

Islets from different regions of pancreases of aging rats were compared for size and variations in response to glucose stimulation. The results show that pancreatic islets from the ventral-duodenal and splenic regions of 12-mo-old retired breeder Spraque-Dawley rats are comparable in all respects measured: thus, pancreatic regional differences cannot explain the age-associated reduction in beta cell secretory response noted in previous studies.     

Diagnostic value of Q-waves in inferior myocardial infarction

Forty-eight patients with proved, healed, inferior myocardial infarction were studied to determine the electrocardiographic characteristics of this syndrome, the correlation between electrocardiographic abnormalities and angiographic findings, and to determine the value of recording Lead III during inspiration to identify abnormal Q-waves.The diagnosis of inferior myocardial infarction (IMI) was established by the presence of two of the following three criteria: (1) past history of acute infarction, associated with typical acute electrocardiographic changes and compatible clinical data, (2) total occlusion or more than 80 per cent occlusion of the right coronary artery, and (3) contraction abnormalities of the inferior left ventricular wall.Fifteen per cent of patients with inferior myocardial infarction had diagnostic Q-waves in all the three limb Leads II, III, and aV_F, and 29 per cent of patients had no diagnostic Q-waves in any of the three limb leads. Relative frequency of diagnostic Q-waves in inferior myocardial infarction were found to be 70, 43, and 15 per cent in Leads III, aV_F, and II, respectively.One hundred per cent correlation was noted between left ventricular inferior wall asynergy and presence of diagnostic Q-waves in all the limb Leads II, III, and aV_F, but the correlation was low (54 per cent) when none of the limb Leads II, III, and aV_F revealed diagnostic Q-waves.Obtaining Lead III in deep inspiration to differentiate an abnormal Q-wave due to inferior myocardial infarction from a benign Q-wave was not found to be a reliable measure and could result in false-negative diagnosis of inferior myocardial infarction in a significant number of patients.     

Echocardiographic assessment of cardiovascular abnormalities in the Marfan syndrome. Comparison with clinical findings and with roentgenographic estimation of aortic root size

Echocardiographic abnormalities of the mitral valve and aortic root were compared with auscultatory findings and with assessment of aortic root size by chest roentgenography in 61 patients with the Marfan syndrome. Echocardiography was more sensitive than physical examination in detecting valvular and aortic root abnormalities. Although physical examination revealed findings of mitral valve disease and/or of aortic regurgitation in 52 percent of patients (mitral valve disease in 44 percent and aortic regurgitation in 23 percent), echocardiography detected abnormalities of the mitral valve and/or aortic root in 82 percent of patients (mitral valve prolapse in 57 percent and aortic root enlargement in 69 percent). Prevalence of mitral valve prolapse was approximately equal in male and female patients, whereas aortic root enlargement was more frequent in males (83 percent) than in females (50 percent). Echocardiographically detected aortic root enlargement was frequently not apparent on chest x-ray films. Indeed, five patients with markedly increased aortic root diameters (ranging from 6.0 to 7.9 cm) had no evident enlargement of the aortic root on routine chest x-ray films. In all four of those patients who had angiographic and/or pathologic correlations, confirmation of marked aortic root dilatation was obtained. There are limitations to echocardiographic evaluation of the presence and severity of underlying cardiovascular disease in patients with the Marfan syndrome. Mitral valve disease may not be detected, especially in patients with left ventricular dilatation. In addition, due to anteroposterior compression of the left atrium by the enlarged aorta, left atrial size may be underestimated in patients with aortic root enlargement.     

Reappraisal of the role of insulin in hypertriglyceridemia

We have previously proposed a sequential hypothesis to help explain the genesis of endogenous hypertriglyceridemia in man. This scheme states that insulin resistance → hyperinsulinemia → increased very low density lipoprotein (VLDL)-triglyceride (TG) production rate → increased plasma TG levels. In this study we have measured each of these metabolic variables in 34 nonobese subjects all consuming the same isocaloric diet. We have found highly significant positive correlations between insulin resistance and insulin response (r = 0.74, p < 0.0001), between insulin response and VLDL-TG production rate (r = 0.72, p < 0.0001), and between VLDL-TG production rate and plasma TG level (r = 0.88, p < 0.0001). Furthermore, these relationships were found to be independent of any possible effect of obesity. Thus, highly positive correlations were found for each step of the scheme, and we believe the over-all hypothesis is greatly strengthened. Additionally, the cross correlation between plasma TG levels and insulin response was also highly significant (r = 0.73, p < 0.0001). On the other hand, glucose response did not correlate with any measure of TG metabolism. On the basis of these results we conclude that insulin plays an important role in the genesis of endogenous hypertriglyceridemia through its influence on VLDL-TG production.