"Silent" myocardial ischemia during and after exercise testing in patients with coronary artery disease

Although many patients with coronary artery disease (CAD) have a positive exercise test without pain, the frequency and significance of this "silent" ischemia is unclear. Therefore, we studied 122 consecutive clinically stable patients with angiographically defined CAD (greater than 75 per cent luminal stenosis) and a positive exercise test. Seventy-eight patients had pain or anginal equivalent during or after a positive exercise test; 44 did not, including 32 (26 per cent) with no symptoms at all. Patients were evaluated as to age, sex, prior myocardial infarction, congestive failure, hypertension, diabetes mellitus, and digoxin or propranolol therapy--in addition to anginal symptoms before, during, or after the exercise itself. Extent of CAD, presence of collaterals, and left ventricular ejection fraction were also determined. All exercise tests were evaluated for evidence of ST-T abnormalities or prior infarction on the control ECG as well as peak heart rate during exercise and post-exercise degree of ST segment depression. There were no significant differences between patients with and without exercise-induced pain in regard to any of the clinical and angiographic features noted above, demonstrating that "silent" myocardial ischemia during or after exercise testing is not uncommon and is not readily attributable to any obvious clinical or catheterization findings. Further studies are necessary to determine if patients with evidence of "silent" myocardial ischemia are especially prone to sudden death.     

Reproducibility of the angiographic left ventricular ejection fraction in patients with coronary artery disease

Quantitative analysis of the single and repeated cine left ventriculogram was performed in 20 patients with coronary artery disease to determine both the intrinsic variance of individual beats separated by different time intervals and variance between analyses of different observers. In addition, ventriculograms obtained from left ventricular injections of contrast medium prior to coronary arteriography were compared to ventriculograms obtained from either left ventricular or pulmonary artery injections after arteriography. The time period between studies varied from 30 minutes to 90 minutes to four days. Analysis of the same ventriculogram by different observers resulted in an average difference in ejection fraction of 0.05 (pNS). The average difference in ejection fraction was 0.02 between two early beats of the same ventriculogram (pNS). The average difference between sequential ventriculograms was 0.07 (pNS), but individual variations greater than 0.10 were not uncommon, particularly between studies done before and after arteriography, or several days apart. Patients exhibiting wide variance in ejection fractions between two studies either had wide variance in other hemodynamic measurements or degree of asynergy, or both. This study provides a frame of reference for analysis of sequential ventriculograms in patients with coronary artery disease, especially in evaluating changes in the state of the disease or the effects of therapy. It is especially important that: (1) standard hemodynamic measurements be made before ventriculography, (2) the same radiographic techniques repeated whenever possible, and (3) the same person analyze the two ventriculograms.     

Comparison of the two-step and maximal exercise tests in patients with coronary artery disease

This study has investigated the claim that the electrocardiographic response to the maximal exercise test provides a more accurate method of assessing the presence and severity of coronary artery disease than the electrocardiographic response to the two-step test. One hundred and one men with a chest pain syndrome underwent the two-step test, maximal exercise test and coronary angiography during the same admission. There was a preponderance of men who performed the maximal exercise test as a result of a negative two-step test. A positive two-step test was defined as horizontal or downsloping S-T segment depression of 0.5 mm or more, whereas a positive maximal exercise test was defined as similar S-T segment depression of 1.0 mm or more. Of the 17 men with no or insignificant coronary artery disease, 5 had a positive two-step test and 6 a positive maximal exercise test. Of the 84 men with coronary artery disease, 33 had a positive two-step test and 38 a positive maximal exercise test. Thus, the specificity of the two-step test for coronary artery disease was 87 percent and that of the maximal exercise test was 86 percent; the respective sensitivity rates were 39 and 45 percent. The percentage of positive results of both exercise tests increased similarly with the severity of coronary artery disease.Nine patients, eight of whom had coronary artery disease, had a positive maximal exercise test but a negative two-step test; in these patients the maximal heart rate was significantly higher during the maximal exercise test than during the two-step test. Five patients, all with coronary artery disease, had a positive two-step test but a negative maximal exercise test. One patient manifested 0.5 mm S-T segment depression in both tests and was thus judged to have a positive two-step test and a negative maximal exercise test. In another patient results were positive in lead V₄ of the two-step test, a lead not recorded in the maximal exercise test. The other three patients had had positive results in a second maximal exercise test recorded in the supine position, thus demonstrating that in certain cases the effects of augmented venous return in the supine position may be as important a factor in eliciting ischemia as the achieved heart rate.     

Prognostic importance of anginal symptoms in angiographically defined coronary artery disease

To evaluate the prognostic importance of anginal symptoms, 44 patients with angiographically defined coronary artery disease and no anginal symptoms at time of cardiac catheterization were selected from the Duke Harvard Collaborative Data Bank. They were “matched” with 127 symptomatic patients in the Data Bank who had similar coronary anatomy and ventricular function. Follow-up data indicated that the patients without anginal symptoms had a significantly better prognosis over a 7 year period than did those with symptoms: Annual mortality in the asymptomatic group was 2.7 percent compared with 5.4 percent in the group with angina (p 0.05). Although the patient population was a highly selective one and the matching categories were relatively broad, these results suggest that the presence of anginal symptoms may be an important independent correlate of prognosis in patients with coronary artery disease. The absence of angina did not preclude the presence of multivessel disease and did not necessarily imply a benign prognosis, because the yearly mortality rate was nearly 5 percent in the subgroup of asymptomatic patients with three vessel disease.     

Effect of coronary collateral vessels on regional myocardial blood flow in patients with coronary artery disease: Relation of collateral circulation to vasodilatory reserve and left ventricular function

The effect of radiographically graded coronary collateral vessels on regional myocardial blood flow was evaluated with intracoronary injection of xenon-133 at rest and during contrast agent-induced coronary hyperemia in 24 patients with coronary artery disease. Eleven patients had no coronary collateral vessels demonstrated radiologically, whereas 13 had such vessels. In 7 of the 13 these were high grade and noncompromised, whereas in 6 they were of lesser grade. Regional myocardial blood flow at rest in patients with and without collateral channels was similar and increased during hyperemia. However, the increase in flow was significantly greater in the patients with high grade noncompromised collateral vessels than in those with lesser grade collateral vessels (80 ± 16 versus 31 ± 9 percent, p <0.05). To evaluate the functional significance of the high grade noncompromised collateral vessels against that of vessels of lesser grade, various indexes of global and regional ventricular function were compared in the 13 patients in the present study, as well as in 24 patients whose collateral vessels had been subjected to similar grading systems in previous studies of regional myocardial blood flow. There were no significant differences in degree of regional asynergy, ejection fraction or left ventricular end-diastolic pressure between the patients with high and lower grades of collateral vessels. Thus, high grade noncompromised collateral vessels do not appear to have a beneficial effect on resting left ventricular function despite their enhanced vasodilatory reserve.     

Therapy of coronary vasoconstriction in patients with coronary artery disease

Patients with obstructive coronary artery disease and stable, exertional angina respond to the alpha adrenergic stimulus of the cold pressor test with an inappropriate increase in coronary vascular resistance. The clinical significance of this abnormal response and its possible role in the pathogenesis of ischemic heart disease are discussed. Comparison of the anti-anginal agents currently in use of undergoing investigation suggests that the calcium antagonists may be the most effective therapy for coronary vasoconstriction. Nifedipine, 10 mg buccally, successfully prevented the increase in coronary vascular resistance during the cold pressor test in 10 of 10 patients, whereas the response in placebo-treated patients was unaltered. This dose of nifedipine was without effect on systemic hemodynamics or myocardial oxygen consumption, suggesting a selective antivasoconstrictor effect on the coronary vasculature.     

Value of a noninvasively induced ventricular extrasystole during echocardiographic and phonocardiographic assessment of patients with idiopathic hypertrophic subaortic stenosis

Fifteen patients with idiopathic hypertrophic subaortic stenosis had a ventricular extrasystole induced with a new external mechanical cardiac stimulator during noninvasive evaluation of left ventricular outflow tract obstruction. Ten patients were monitored with simultaneous echocardiogram, phonocardiogram and indirect carotid pulse tracing; five were monitored with the phonocardiogram and indirect carotid pulse tracing alone. Nine of the 15 patients showed obstruction in the beat after the ventricular extrasystole, as defined by appearance of the characteristic bifid carotid pulse contour and, where recorded, an increase in systolic anterior motion of the mitral valve on echocardiography. Six patients did not show obstruction. All nine patients with obstruction had greater than 20 msec prolongation of uncorrected systolic ejection time in the post-extrasystolic beat of the carotid pulse tracing. Change in the uncorrected ejection time was + 0.038 ± 0.015 second (mean ± standard deviation) in these nine patients compared with − 0.003 ± 0.005 second in the six not showing obstruction (P < 0.01). Six patients underwent cardiac catheterization: Three patients without obstruction after a noninvasively induced ventricular extrasystole had no obstruction at catheterization and three patients with obstruction after noninvasively induced ventricular premature beats demonstrated obstruction at rest or after provocative maneuvers during catheterization. These results indicate that the noninvasive induction of a ventricular extrasystole is a useful and easily performed procedure for both diagnosing and evaluating the dynamic left ventricular outflow tract obstruction of idiopathic hypertrophic subaortic stenosis.     

Effect of sublingually administered nitroglycerin on regional myocardial blood flow in patients with coronary artery disease.

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.     

Left ventricular ejection fraction as a prognostic guide in surgical treatment of coronary and valvular heart disease

The immediate and short-term prognostic values of increased left ventricular end-diastolic pressure, reduced cardiac index and depressed ejection fraction determined during preoperative evaluation were compared in 128 patients undergoing coronary revascularization and 44 patients undergoing cardiac valve replacement. A modification of the New York Heart Association (NYHA) functional classification was used to evaluate pre- and postoperative left ventricular decompensation. One hundred fifty-eight of the 172 patients did well postoperatively (NYHA classes I and II), including the majority of patients with either an abnormal left ventricular end-diastolic pressure (> 15 mm Hg), reduced cardiac Index (< 2.5 liters/min per m²) or depressed ejection fraction (< 0.50). However, of the 14 patients who did not survive surgery or had progressive postoperative deterioration, 10 had a depressed ejection fraction and 7 had combined abnormalities of left ventricular end-dlastolic pressure and cardiac index. Because these latter values may often be borderline, or occur as isolated abnormal findings, the ejection fraction is probably the most useful of the readily obtainable, single hemodynamic measurements in assessing the import of deranged left ventricular function on the outlook for patients undergoing cardiac surgery.     

Inappropriate coronary vasoconstriction in patients with coronary artery disease: A role for nifedipine?

Coronary arterial vasoconstriction, well recognized in Prinzmetal's variant angina, may participate in the pathogenesis of classic angina as well. Several recent studies in patients with obstructive coronary artery disease suggest that apparently spontaneous reductions in coronary blood flow can result in myocardial ischemia and even infarction. Evidence supporting the alpha adrenergic nervous system as a cause of such coronary vasoconstriction is reviewed, particularly the results of provocative testing with the cold pressor stimulus. Upon exposure of the skin to cold, patients with coronary artery disease demonstrate an inappropriate coronary vasoconstrictor response, often sufficient to produce angina. Normal patients, by contrast, show no change in coronary vascular resistance. In patients with a diseases coronary circulation, inappropriate vasoconstriction further restricts myocardial perfusion and appears to be little affected by beta adrenergic blocking agents or nitrates in the usual dosages. Nifedipine has proved effective in preventing coronary arterial spasm in patients with Prinzmetal's angina. Studies currently in progress suggest that it is also effective in blocking inappropriate coronary vasoconstriction in patients with typical angina. Nifedipine may thus be a useful addition to the treatment of ischemic heart disease.     

Echocardiography.

We have discussed the evolution of selected areas of echocardiography in an attempt to illustrate the capabilities and limitations of this method of study. As information has accumulated, some concepts of the specificity of certain echocardiographic patterns have had to be revised. Awareness of the potential for false positive and false negative results has increased rather than decreased the usefulness of the echo method. Equipment deficiencies which existed in past years have largely been corrected, thereby reducing the likelihood of repeating some of the earlier mistakes. Two years ago, we suggested that more patients with left ventricular disease should be studied, the results from different laboratories should be compared, a large number of patients with congenital disease should be evaluated, and the limitations of the technic be more precisely defined. Obviously much has been accomplished in all of these areas. Much more can be done. There is every reason to believe that the next few years will bring many new and important developments in diagnostic echocardiography.     

Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion.

In anesthetized open chest dogs, hydrocortisone (50 mg/kg body weight administered 30 minutes after occlusion and 25 mg/kg 12 hours later) substantially reduced the size of myocardial infarcts, as reflected by both myocardial creatine phosphokinase activity and histologic appearance 24 hours later. Similarly, hyaluronidase, which increases diffusion through the extracellular space and presumably facilitates delivery of substrate to ischemic cells, also reduced the extent of myocardial necrosis after coronary occlusion in the dog. In view of the salutary effects of hyaluronidase and the absence of serious side effects, this agent was administered clinically to two groups of patients, who were compared with two groups of untreated control subjects. Hyaluronidase (500 National Formulary units/kg X 8) was shown to result in a significantly more rapid reduction in the magnitude and the extent of precordial S-T segment elevations, and in patients treated within 4 hours a tendency to a lower incidence rate of Q waves and a smaller reduction of R waves.