Effect of isosorbide dinitrate on response to submaximal and maximal exercise in patients with congestive heart failure.

Isosorbide dinitrate is an effective vasodilator that improves resting left ventricular performance in patients with congestive heart failure, but little is known of the effect of the drug on the response to exercise. Bicycle exercise to symptomatic maximum was performed by 18 patients with class II to IV congestive heart failure before and 90 minutes after administration of isosorbide dinitrate, 40 mg orally. Although resting pulmonary wedge pressure and systemic vascular resistance were significantly reduced after isosorbide dinitrate, exercise duration was not altered and maximal oxygen consumption was not significantly changed (13.6 +/- 1.3 [SEM] standard error of the mean versus 13.8 +/- 1.2 ml/kg per min). At peak exercise pulmonary wedge pressure of 37.1 +/- 1.7 mm Hg, cardiac index of 4.19 +/- 0.35 liters/min per m2, and systemic vascular resistance of 14.7 +/- 1.3 units were not significantly different after nitrate administration. However, at submaximal loads, pulmonary wedge pressure was reduced from 33.6 +/- 1.7 to 27.9 +/- 1.8 mm Hg (P less than 0.01), and systemic resistance from 16.5 +/- 1.5 to 13.7 +/- 1.0 units (P less than 0.01) after administration of isosorbide dinitrate. Thus, short-term administration of nitrates does not improve maximal exercise capacity or left ventricular performance at maximal exercise in patients with congestive heart failure, but it does appear to improve pump function at submaximal work loads and may therefore enable patients to perform limited exercise more comfortably.     

Serum high density lipoprotein cholesterol correlates with presence but not severity of coronary artery disease

An elevated serum level of low density lipoprotein (LDL) is a risk factor for the development of coronary artery disease, whereas elevated levels of high density lipoprotein (HDL) appear to have a protective effect, and the total cholesterol to HDL ratio has been suggested as an improved method for assessing risk. We determined cholesterol, HDL and triglycerides in 189 patients undergoing diagnostic cardiac catheterization to determine if these variables correlate with the severity of coronary artery disease assessed as the number of major coronary vessels having ≥ 70 percent stenosis. HDL was higher in the group with zero vessel disease (54 ± 2.3 mg/dl ± SEM) than in those with one, two or three vessel disease (43 ± 1.8, 45 ± 1.8 and 51 ± 1.2, respectively), and the cholesterol to HDL ratio was lower in the group with zero vessel disease (4.1 ± 0.2 compared to 6.1 ± 0.3, 5.7 ± 0.2 and 6.4 ± 0.3 in the groups with 1, 2 and 3 vessel disease).Using analysis of variance, patients with no coronary artery disease (zero vessel disease) differed from those with coronary artery disease in HDL (p < 0.005), triglycerides (p > 0.01), cholesterol (p < 0.005) and cholesterol to HDL (p > 0.005), but no significant differences were found between patients with coronary artery disease and a different number of vessels involved. There were no significant differences between the groups in age, and although the group with zero vessel disease had more females than the others, there were no differences in cholesterol, HDL, cholesterol to HDL ratio, or triglycerides between male and female patients with no coronary artery disease. We conclude that the cholesterol to HDL ratio correlates with the presence but not severity of coronary artery disease.     

Response of plasma norepinephrine and epinephrine to dynamic exercise in patients with congestive heart failure

The activity of the sympathetic nervous system is increased at rest in patients with congestive heart failure. To determine whether this augmentation is carried over during dynamic upright exercise, 14 patients with congestive heart failure were stressed maximally during upright bicycle ergometry. Plasma norepinephrine and epinephrine levels were measured in the basal upright (sitting) posture before and during maximal exercise. The results were compared with those in six healthy control subjects before and during maximal exercise. Plasma norepinephrine increased during exercise from a mean (± standard error of the mean) of 650 ± 95 to 1,721 ± pg/ml in the group with heart failure. This increase was significantly less (p < 0.001) than that in the control group (from 318 ± 36 to 3,230 ± 418 pg/ml). However, for equivalent levels of total body oxygen consumption (V?O₂), the group with heart failure had higher levels of plasma norepinephrine than the control group. Plasma epinephrine was similar in the two groups in the basal upright position (92 ±18 and 92 ± 26 pg/ml), but it increased more during exercise in the normal subjects (743 ± 210 pg/ml) than in the group with heart failure (167 ± 67 pg/ml) (p < 0.001). The percent increase in norepinephrine correlated with the percent change in V?O₂ in the group with heart failure (r = 0.62, p < 0.02), but the percent change in epinephrine did not.There is, therefore, a disturbance in the sympathetic nervous system during exercise in patients with congestive heart failure. Although norepinephrine increases in such patients to a greater extent than in normal subjects at lower levels of exercise, the extremely high levels of norepinephrine and epinephrine generated by normal subjects during maximal upright exercise do not occur in patients with heart failure.     

Relative attenuation of sympathetic drive during exercise in patients with congestive heart failure

Patients with congestive heart failure have been considered to have augmented sympathetic drive both at rest and during dynamic exercise. The augmentation observed during exercise may be related to the state of near exhaustion experienced by patients with heart failure at relatively low work loads. To compare the response of the sympathetic nervous system to exercise in normal subjects and patients with heart failure when they are working in a comparable physiologic frame of reference, the data for both groups can be expressed as percent peak oxygen consumption achieved (percent peak VO2) rather than as a function of absolute oxygen consumption (VO2). Ten healthy control subjects and 31 patients with chronic clinical class II and III heart failure were studied during upright maximal bicycle exercise. Eighteen of the 31 patients had primary cardiomyopathy and 13 had ischemic cardiomyopathy. The average ejection fraction at rest was 24 +/- 10% (+/- SD) in the group with heart failure. Heart rate, systolic blood pressure, VO2 and plasma norepinephrine levels were measured at rest and throughout exercise. When the data were expressed as a function of percent peak VO2 achieved, patients with heart failure demonstrated a flatter slope (p = 0.004) than normal in the response of plasma norepinephrine to exercise, indicating a relative blunting of sympathetic drive. This was accompanied by attenuated heart rate (p = 0.001) and blood pressure (p less than 0.001) responses. These differences were not apparent when the data are expressed as a function of absolute VO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

"Maximal" drug therapy is not necessarily optimal in chronic angina pectoris

Beta-adrenergic blocking agents, nitrates and calcium channel antagonists are effective in treating angina pectoris, but much remains unknown about how they act in combination. Consequently, treadmill exercise was used to assess the relative efficacy of nifedipine or isosorbide dinitrate, or both, in 19 patients with stable angina receiving propranolol. Propranolol therapy was continued and either placebo, nifedipine (20 mg), isosorbide dinitrate (20 mg) or both drugs were given randomly 1 1/2 hours before exercise in a double-blind trial. In 16 patients who completed the protocol, heart rate at rest during propranolol therapy was 53.7 +/- 1.9 beats/min (mean +/- standard error of the mean); it increased 4.6 +/- 1.2 beats/min with the addition of nifedipine (p less than 0.01), but was unchanged with isosorbide dinitrate or both combined. Compared with values during treatment with propranolol alone, systolic blood pressure at rest decreased with each vasodilator individually and when combined. Rate-pressure product at maximal exercise was the same with all combinations. Exercise duration was 467 +/- 50 seconds with propranolol, increased to 556 +/- 47 seconds with isosorbide dinitrate (p less than 0.05) and to 636 +/- 50 seconds with nifedipine (p less than 0.001). Exercise duration with all three drugs was 597 +/- 47 seconds (p less than 0.01 compared with propranolol alone). The improvement with nifedipine was greater than with isosorbide dinitrate (p less than 0.05) but exercise duration was not significantly different with the combination of these drugs than when either drug was used alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated left ventricular myocardial dopamine in preterminal idiopathic dilated cardiomyopathy

The adrenergic nervous system is chronically activated in patients with congestive heart failure (CHF). One consequence of this is depletion of the normally high levels of myocardial norepinephrine. In this study, myocardial norepinephrine and dopamine concentrations from the left ventricular walls of 3 patients undergoing cardiac transplantation for severe refractory CHF are reported. The dopamine/norepinephrine ratios were high in all 3 patients (29, 58 and 26%). This finding supports data from animal studies suggesting a change in the rate-limiting step for myocardial norepinephrine synthesis in CHF. Conversion of tyrosine to dopa by tyrosine hydroxylase is replaced as the rate-limiting step by inability to hydroxylate dopamine to norepinephrine. Thus, dopamine accumulates while norepinephrine is depleted.     

Effects of isosorbide dinitrate and hydralazine on regional metabolic responses to arm exercise in patients with heart failure

The reduced exercise capacity of patients with heart failure is thought to be due in part to impaired skeletal muscle oxygen delivery. To determine if hydralazine and isosorbide dinitrate improve skeletal muscle oxygen delivery in such patients, the effects of these agents on regional metabolic responses to forearm exercise were examined in 16 patients with heart failure. Arm oxygen extraction and brachial venous lactate concentration were measured at rest and during 3 minutes of rhythmic handgrip and then remeasured after administration of oral hydralazine (nine patients) or sublingual isosorbide dinitrate (nine patients). Hydralazine increased mean (± standard deviation) cardiac output at rest from 3.5 ± 0.5 to 4.9 ±1.0 liters/min (p < 0.01) and decreased arm oxygen extraction from 39 ± 8 to 33 ± 10 percent (probability [p] < 0.01), suggesting improved resting limb oxygen delivery. However, hydralazine did not reduce arm oxygen extraction during exercise (control 63 ± 4, hydralazine 60 ± 12 percent; p = notsignificant[NS]) or venous lactate during exercise (control 16.6 ± 7.8, hydralazine 17.1 ± 4.8 mg/100 ml; p = NS). Isosorbide dinitrate increased the cardiac output from 3.6 ± 0.7 to 4.5 ± 0.7 liters/min (p < 0.01) but had no effect on arm oxygen extraction at rest (control 40 ± 11, isosorbide dinitrate 38 ± 11 percent; p = NS) and during exercise (control 66 ± 5, isosorbide dinitrate 64 ± 8 percent; p = NS) or on venous lactate during exercise (control 17.9 ± 6.4, isosorbide dinitrate 17.1 ± 3.9 mg/100 ml; p = NS). These data suggest that hydralazine and isosorbide dinitrate do not improve skeletal muscle oxygen delivery during exercise in patients with heart failure.     

Comparative effects of nifedipine, verapamil, and diltiazem on experimental pulmonary hypertension

The role of calcium-channel blocking agents in the treatment of pulmonary hypertension is not well defined. Consequently, the effects of diltiazem, nifedipine, and verapamil were compared in 3 groups of anesthetized dogs (n = 6 for each group). In each group, normoxic hemodynamic variables were recorded before and after increasing doses of diltiazem, nifedipine, and verapamil (5 X 10(-8) M/kg, low; 10(-7) M/kg, medium; and 10(-6) M/kg, high dose; given intravenously over 2 minutes). In addition, the effect of these doses on the pulmonary pressor responses to hypoxia (fractional inspired oxygen concentration [FIO2] 12%) and prostaglandin F2 alpha (PGF2 alpha) (5 micrograms/kg/min, intravenously for 4 minutes) was measured. During normoxia, high-dose nifedipine and verapamil decreased mean aortic pressure and systemic vascular resistance while increasing cardiac output in all dogs in both groups (p less than 0.01). Pulmonary vascular resistance, however, remained unchanged. High-dose diltiazem did not significantly alter cardiac output or pulmonary vascular resistance. During acute hypoxic pulmonary hypertension, verapamil decreased cardiac output by 30% (p less than 0.01) without appreciably altering pulmonary arterial pressure; thus pulmonary vascular resistance increased slightly (4.9 +/- 0.6 to 6.4 +/- 1.0 mm Hg/liter/min, difference not significant [NS]). Nifedipine decreased hypoxic pulmonary vascular resistance to normoxic values (p less than 0.01). Cardiac output increased 71% while pulmonary arterial pressure remained unchanged. Diltiazem administration produced no change in hypoxic pulmonary hemodynamic variables. The responses to diltiazem, nifedipine, and verapamil during acute pulmonary vasoconstriction induced by PGF2 alpha were similar to those induced by hypoxia. After verapamil, pulmonary vascular resistance tended to increase (7.3 +/- 1.3 to 8.1 +/- 1.4 mm Hg/liter/min, NS). Nifedipine, however, completely blocked pulmonary vasoconstriction by decreasing pulmonary vascular resistance to pre-PGF2 alpha levels (p less than 0.01). This was accompanied by a 157% increase in cardiac output and only a small increase in pulmonary arterial pressure (7 mm Hg). Again, diltiazem produced no change in pulmonary hemodynamic variables. In these acute studies, nifedipine appeared to be a more effective pulmonary vasodilator than verapamil or diltiazem.     

Randomized, placebo-controlled evaluation of lidoflazine in patients receiving beta-blocker therapy with propranolol: improvement in anginal symptoms and exercise tolerance with combined drug therapy

To evaluate the timing of the right ventricular (RV) apical electrogram in relation to the QRS complex during ventricular tachycardia (VT), 94 episodes of sustained uniform VT were analyzed in 56 patients. The timing of the RV apical electrogram varied and could be recorded from 33 ms before to 180 ms (mean 77 +/- 44 ms) after the onset of the QRS complex. The timing of the RV apical electrogram, expressed both as an absolute value and as a percentage of a QRS width, was significantly different when right bundle branch block (BBB) morphology VT (95 +/- 37 ms) and left BBB morphology VT (40 +/- 341) were compared (p less than 0.001). The timing of the RV apical electrogram, expressed as a percentage of the QRS width, was significantly different when VT with different axes were compared in the right BBB VT group (p less than 0.01). A left BBB VT, as compared to a right BBB VT, predicted an RV apical electrogram occurring in the first 35% of the QRS with a sensitivity of 74%, a specificity of 91%, and a positive predictive value of 84%. Right BBB VT with a right and inferior axis were usually associated with the latest occurring RV apical electrogram. A right BBB VT with a right and inferior axis predicted an RV apical electrogram inscribed in the latter half of the QRS with a sensitivity of 65%, a specificity of 84% and a positive predictive value of 80%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blind crossover comparison of the antianginal effects of nifedipine and isosorbide dinitrate in patients with exertional angina receiving propranolol

A double-blind crossover study was performed on 27 patients with proved fixed coronary artery disease and stable angina pectoris. The study was designed to compare the relative efficacy of two combination therapies, nifedipine plus propranolol and isosorbide dinitrate plus propranolol, in terms of antianginal response and effect on exercise tolerance by evaluation of treadmill testing. The combination of nifedipine and propranolol was superior to the combination of isosorbide and propranolol in reducing the number of anginal attacks (p = 0.03), increasing total exercise time (p less than 0.02), increasing oxygen consumption achieved at end of exercise (p less than 0.03), increasing time to onset of pain (p = 0.003) and increasing oxygen consumption achieved at onset of pain (p = 0.003). Analysis of the rate-pressure products suggests that the difference in these results may be explained by the greater effect of nifedipine on afterload reduction. Although nitroglycerin consumption was reduced from baseline levels during combination nifedipine therapy (p less than 0.001), there was no statistical difference between nifedipine combination therapy and isosorbide combination therapy. In conclusion, although both combination therapies were superior to propranolol therapy alone, the combination of nifedipine and propranolol was more effective than the combination of isosorbide and propranolol in reducing the incidence of angina and improving exercise performance. Side effects were experienced at a similar frequency during both combination therapies.     

Myocardial imaging with thallium-201: a multicenter study in patients with angina pectoris or acute myocardial infarction

A multicenter study of rest and exercise thallium-201 myocardial imaging in 190 patients from five centers was performed. Exercise images were obtained after graded treadmill or bicycle stress with use of five different gamma camera models and were interpreted by the originating investigator without knowledge of other clinical data. Of 42 patients with less than 50 percent coronary stenosis, 4 (10 percent) had a resting image defect, 1 (2 percent) a new exercise defect and 5 (12 percent) either a resting or an exercise image defect, or both. Of 148 patients with coronary stenosis of 50 percent or greater, 64, (45 percent) had an image defect in the study at rest, 90 (61 percent) had new or increased defects after exercise, and 115 (78 percent) had resting or exercise defects, or both. New exercise image defects were more common than exercise S-T depression (90 of 148 [61 percent] versus 62 of 148[42 percent]; P less than 0.01). In a second group of 111 patients with acute myocardial infarction studied at three centers, 90 patients (81 percent) had image defects compared with 71 (64 percent) two had new electrocardiographic Q waves (P less than 0.01). Smaller infractions, as assessed with serum enzyme values, and diaphragmatic infarctions were less commonly detected than larger or anterior infarctions. These findings suggest that myocardial imaging complements the electrocardiographic identification of acute myocardial infarction of exericse-induced myocardial ischemia.     

Improved efficacy of high-dose versus medium- and lowdose diltiazem therapy for chronic stable angina pectoris

The efficacy of therapy with diltiazem, 360 mg/day, was studied in 11 men with chronic, stable angina pectoris. An initial dose-titration schedule in which diltiazem was increased weekly from placebo to 120, 240 and 360 mg/day (Period I) was followed by a randomized, double-blind, 1-month crossover trial of placebo vs diltiazem at 360 mg/day (Period II). A computer-assisted treadmill exercise test was performed at the end of each dose and each 2-week crossover period. Diltiazem at 360 mg/day, compared with placebo (Period II), significantly improved exercise performance. Exercise duration to onset of chest pain increased 40% from 5.3 ± 2.1 to 7.4 ± 2.7 minutes (p < 0.01). Time to reach 1 mm of ST-segment depression increased 33%, from 5.1 ± 2.0 to 6.8 ± 1.8 minutes (p < 0.01). Total exercise duration increased 16%, from 7.5 ± 2.0 to 8.7 ± 2.0 minutes (p < 0.005). A computer-derived quantitative treadmill exercise score improved 27%, from ? 13.1 ± 9.4 to ? 9.5 ± 7.6 units (p < 0.005), and the ST-segment depression at peak exercise improved from ? 1.9 ± 1.1 to ? 1.6 ± 1.2 mm (p < 0.05). Progressive improvement in these variables was seen during the single-blind dose-titration period between 120 and 240 mg/day and between 240 and 360 mg/day (Period I). Baseline heart rate (HR) and diastolic blood pressure (BP) in the supine and upright position were significantly lower with diltiazem than with placebo. Diltiazem decreased the supine HR at rest from 67 ± 14 to 60 ± 10 beats/min (p < 0.05) and the upright HR at rest from 77 ± 14 to 69 ± 13 beats/min (p < 0.005). Diastolic BP at rest in the supine position decreased from 81 ± 6 to 75 ± 7 mm Hg (p < 0.05) and in the upright position from 82 ± 9 to 76 ± 8 mm Hg (p < 0.05). Thus, diltiazem improved exercise tolerance and exerciseinduced myocardial ischemia and showed good dose-response characteristics at doses as high as 360 mg/day in patients with stable angina pectoris.     

Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects

Serial hemodynamic and plasma catecholamine responses were compared among 10 healthy men (27 +/- 3 years) (+/- 1 standard deviation) during symptom-limited handgrip (33% maximal voluntary contraction for 4.4 +/- 1.8 minutes), cold pressor testing (6 minutes) and symptom-limited supine bicycle exercise (22 +/- 5 minutes). Plasma catecholamine concentrations were measured by radioenzymatic assays: ejection fraction and changes in cardiac volumes were assessed by equilibrium radionuclide angiography. During maximal supine exercise, plasma norepinephrine and epinephrine concentrations increased three to six times more than during either symptom-limited handgrip or cold pressor testing. Additionally, increases in heart rate, systolic blood pressure, rate-pressure product, stroke volume, ejection fraction and cardiac output were significantly greater during bicycle exercise than during the other two tests. A decrease in ejection fraction of 0.05 units or more was common in young normal subjects during the first 2 minutes of cold pressor testing (6 of 10 subjects) or at symptom-limited handgrip (3 of 10), but never occurred during maximal supine bicycle exercise. The magnitude of hemodynamic changes with maximal supine bicycle exercise was greater, more consistent and associated with much higher sympathetic nervous system activation, making this a potentially more useful diagnostic stress than either handgrip exercise or cold pressor testing.     

Hemodynamic effects of high-dose sustained-action oral isosorbide dinitrate in stable angina

Hemodynamic effects of sustained-action oral isosorbide dinitrate (40 or 80 mg) were studied in 10 patients with stable angina for a period of 16 hours. Control hemodynamic parameters monitored for eight hours prior to the administration of isosorbide dinitrate showed no significant change. However significant reduction in mean arterial pressure, cardiac index, pulmonary artery wedge pressure, mean pulmonary artery pressure, double product (systolic pressure multiplied by heart rate), stroke volume index, and stroke work index occurred in the first two hours and persisted for 12 hours following the administration of isosorbide dinitrate. Heart rate did not change significantly for 12 hours. It can be concluded that the hemodynamic effects of sustained-action oral isosorbide dinitrate occur in the first two hours and last up to 12 hours. The predominant hemodynamic effect appears to be on the myocardial preload. The antianginal effect of the drug could be attributed to the reduction of myocardial oxygen demand reflected by a decrease in the double product and stroke work. The duration of the hemodynamic changes observed in this study indicates that high-dose oral isosorbide dinitrate could be administered conveniently two or three times daily.     

Echocardiographic evidence for early left ventricular hypertrophy in dogs with renal hypertension

To investigate the rate of development of left ventricular hypertrophy, left ventricular wall thickness was measured with M mode echocardiography in 12 unanesthetized dogs for several weeks before and for 8 weeks after the induction of hypertension. Hypertension was produced by wrapping one kidney in silk and performing contralateral nephrectomy 2 weeks later. Echocardiographic measurements were performed two to three times weekly and were averaged. The intraobserver and Interobserver variability of left ventricular posterior wall thickness measurements was, respectively, 3.9 percent (correlation coefficient [r] = 0.96, n = 27) and 5.4 percent (r = 0.93, n = 14). Left ventricular wall thickness during the baseline period was 7.8 ± 0.2 mm (mean ± standard deviation) with a coefficient of variation of 2.9 percent. After the wrapping of one kidney in silk, the mean arterial pressure increased by 10 mm Hg during week 1 (difference not significant) and by 12 mm Hg during week 2 (p < 0.05). After contralateral nephrectomy, mean arterial pressure increased by 46 mm Hg (p < 0.001) in 1 week and remained near that level for the rest of the study. In contrast, a significant increase in left ventricular wall thickness occurred during week 1 after wrapping (p < 0.05). A gradual increase in left ventricular wall thickness continued during the entire study.

Sequential M mode echocardiography in dogs is a sensitive and reproducible method of detecting small changes in left ventricular wall thickness. The early increase in left ventricular wall thickness in hypertensive dogs with only minimal increase in mean arterial pressure and the dissociation between the rate of development of hypertension and of left ventricular hypertrophy suggest that factors other than the pressure overload also may contribute to the initiation and evolution of cardiac hypertrophy.     

Long-term propranolol therapy for angina pectoris

Sixty-three patients with stable, severe typical angina pectoris (New York Heart Association functional class III or IV) were treated with propranolol and studied prospectively with a follow-up period of 5 to 8 years to assess the rate of complications and long-term effectiveness after an initial control period. The patients' mean age was 56 years; the mean daily dose of propranolol was 255 mg. The average yearly mortality rate was 3.8 percent with a cumulative 5 year mortality rate of 19 percent. Patients whose reduction of angina with propranolol was less than 50 percent had a nearly four-fold greater mortality rate than those whose reduction was 50 percent or more (P < 0.01). Thirtytwo percent of patients per year were angina-free with propranolol and 84 percent per year had 50 percent or more reduction in anginal episodes. There was no evidence for tachyphylaxis. Heart failure developed in 25 percent of patients, two thirds of whom had either congestive heart failure with an acute infarction or a prior history of congestive heart failure. All patients whose initial cardiothoracic ratio was greater than 0.5 had heart failure during the first 3 years of propranolol therapy. Of 12 patients who had an acute infarction during therapy, 7 died, 6 with cardiogenic shock; in contrast, 8 of 9 patients who had congestive heart failure without acute infarction survived. Eight percent of patients had other significant side effects, including gastrointestinal symptoms (three patients), hallucinations (one) and postural hypotension (one). The occurrence of asthma in three patients was dose-related and did not require drug discontinuation.Propanolol is an effective form of long-term therapy for severe angina pectoris; it does not induce tachyphylaxis or increase the overall mortality rate, although it may increase the risk of cardiogenic shock in acute myocardial infarction. Previous history of congestive heart failure, a cardiothoracic ratio of more than 0.5 without overt heart failure and mild asthma are relative contraindications. A 50 percent or greater reduction in anginal pain with propranolol predicts a low mortality group.     

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)     

Spatial R wave amplitude changes during exercise: relation with left ventricular ischemia and function

Thirty patients who exhibited increased and 65 patients decreased spatial R wave amplitude during exercise testing were compared for left ventricular function and ischemic variables. Spatial R wave amplitude was derived from the three-dimensional Frank X, Y, Z leads using computerized methods. All patients had stable coronary artery disease and they were classified into two groups: one that attained a higher (n = 48) and one a lower (n = 47) median value of maximal heart rate during exercise (161 beats/min). Within these two groups, patients with increasing or decreasing spatial R wave amplitude during exercise were analyzed for differences in oxygen consumption, exercise-induced changes in spatial R wave amplitude, ST segment depression laterally (ST60, lead X), ST displacement spatially, left ventricular ejection fraction at rest, change in left ventricular ejection fraction with exercise and thallium-201 ischemia during exercise. Significant differences were demonstrated only in exercise-induced spatial R wave amplitude changes (p less than 0.0001). There was no significant correlation between exercise-induced change in heart rate and change in spatial R wave amplitude in either the group with increasing or the group with decreasing spatial R wave amplitude. It is concluded that changes in spatial R wave amplitude during exercise are not related to ischemic electrocardiographic or thallium-201 imaging changes or to left ventricular ejection fraction determined at rest or during exercise.