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.     

Dynamic characterization of premature ventricular beats and ventricular tachycardias

The contraction patterns induced by ectopic ventricular premature beats and ventricular tachycardias occurring in man during left ventriculography were analyzed. These were compared with contraction patterns induced by ventricular premature beats and tachycardias produced in five dogs by epicardial left ventricular apical or basilar stimulation. Two patterns of contraction observed in the animals corresponded to two patterns observed in man. Apically stimulated left ventricular beats produced an “hourglass” type of contraction pattern and were hemodynamically more effective than beats arising from basilar stimulation, which produced an inverse “teardrop” pattern. The same patterns were reproduced by experimental ventricular tachycardias. These observations stress the importance of a normal sequence of ventricular contraction to optimal cardiac function in man and warn against the hazards of misinterpretation of the left ventricular contraction pattern if the beat originates ectopically during ventriculography.     

Natural history of S-T segment elevation after acute myocardial infarction

Clinical, electrocardiographic and cineventriculographic data in two patient groups were analyzed to define the natural history of S-T segment elevation after myocardial infarction. In sixteen of 22 patients (73 percent) with acute inferior myocardial infarction, S-T segment elevation was present on hospital admission, persisting in 1 (5 percent) by the 2nd week. S-T segment elevation was present on admission in 18 of 23 patients (78 percent) with acute anterior myocardial infarction and persisted in 13 after 1 week and in 9 of 14 (64 percent) during a follow-up period of 1 to 6 months. S-T segment elevation lasting more than 2 weeks after myocardial infarction did not resolve. Compared with patients with inferior myocardial infarction or anterior infarction without persistent S-T segment elevation, patients with anterior infarction and persistent S-T segment elevation had a higher level of mean maximal serum creatine phosphokinase (CPK), more severe left ventricular decompensation and a greater frequency of death in the early follow-up period. In a separate series of 95 patients with cineangiographically documented coronary artery disease, 40 of 65 patients (62 percent) with advanced anterior and apical asynergy had persistent S-T segment elevation. By contrast, only 1 of 30 (3 percent) with coronary disease and normal ventriculograms had persistent S-T segment elevation.We concluded that (1) the natural history of S-T segment elevation after myocardial infarction is resolution within 2 weeks in 95 percent of inferior but in only 40 percent of anterior infarctions; (2) S-T segment elevation persisting more than 2 weeks after myocardial infarction does not resolve; (3) persistent S-T segment elevation is associated with clinically more severe myocardial infarction; and (4) in patients with coronary artery disease, persistent S-T segment elevation after myocardial infarction is a specific but insensitive index of advanced asynergy.     

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.     

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.     

Dissection of the thoracic aorta: Medical or surgical therapy?

Both medical and surgical therapy are available for the treatment of aortic dissection. To help determine which form of treatment is indicated for which patients, all cases of aortic dissection at the Peter Bent Brigham Hospital from 1963 to 1973 were reviewed. The most important feature in determining the patient's clinical status and response to therapy was the site of dissection, that is, the ascending or descending aorta.

Of 31 patients with dissection of the ascending aorta, 26 had one or more of the following contraindications to medical therapy: congestive heart failure (8 patients), hemopericardium (8 patients), new aortic insufficiency (13 patients) or jeopardized carotid or coronary arteries (4 patients). Medical therapy was successful in only 1 of 9 patients with dissection of the ascending aorta; 17 of 22 patients having surgical correction of this lesion did well and were discharged.

The clinical status of the 14 patients with dissection limited to the descending aorta was quite different. None had a contraindication to medical therapy. Medical therapy was instituted in all 14, and was successful in 6; dissection progressed in 8 patients despite medical therapy, and subsequent surgery was successful in only 2.

We conclude that the treatment of choice for dissection of the ascending aorta is prompt surgical therapy. In patients with dissection limited to the descending aorta, medical therapy is usually feasible and often successful.     

Clinical significance of coronary arterial ectasia.

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

Regional left ventricular function in acute myocardial infarction: Evaluation with quantitative radionuclide ventriculography

Regional and global left ventricular performance was noninvasively assessed with quantitative gated equilibrium radionuclide ventriculography in 43 patients an average of 40 hours after the onset of a first acute transmural myocardial infarction. In all 16 patients with anterior infarction, regional ejection fraction, a quantitative measure of regional left ventricular performance, was uniformly depressed in the infarcted zone. In patients with inferior infarction the abnormalities of regional performance were less severe. Fourteen of 20 patients (70 percent) with inferior infarction had depressed performance in the infarcted zone. Function in noninfarcted zones was abnormal in only 6 of the 20 patients (30 percent) with inferior infarction, but it was abnormal in 11 of the 16 patients (69 percent) with anterior infarction, particularly in those with severe pump failure. As a consequence, global left ventricular ejection fraction was significantly lower in patients with anterior than in those with inferior infarction (mean ± standard error of the mean 31 ± 3 percent versus 51 ± 3 percent, p < 0.005). Prognosis and clinical functional class were related to performance not only in infarcted zones, but also in noninfarcted zones as assessed with electrocardiography.It is concluded that depressed function in apparently noninfarcted left ventricular zones contributes significantly to left ventricular dysfunction after acute myocardial infarction, particularly in patients with anterior infarction.     

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.     

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.     

Left ventricular end-systolic pressure-dimension and stress-length relations in normal human subjects

To determine whether the left ventricular end systolic pressure-dimension and end-systolic stress-dimension relations in human beings are linear and sensitive to altered contractility, we studied 13 normal subjects during methoxamine infusion and with postextrasystolic potentiation induced by an external mechanical cardiac stimulator. End-systolic diameter was obtained with echocardiography and end-systolic pressure was estimated in six subjects from the dicrotic notch of a simultaneously recorded carotid pulse tracing, standardized by cuff pressure, whereas in seven subjects intraarterial pressure was recorded. For each subject, the end-systolic pressure-dimension relation was linear (r = 0.83–0.99) over a range of 76 mm Hg (84 to 160) for end-systolic pressure. The mean slope of the end-systolic pressure-dimension line was 62 ± 22 mm Hg/cm. Peak systolic pressure was also linearly related to end-systolic diameter (r = 0.82–0.99) over a range of 100 mm Hg (104 to 204). End-systolic stress was a linear function of end-systolic dimension as well (r = 0.93–0.99) over an end-systolic stress range of 181 g/cm². With postextrasystolic potentiation the potentiated beat had a smaller end-systolic dimension for any given end-systolic pressure and thus shifted the end-systolic pressure-dimension relation to the left. Thus, end-systolic pressure-dimension and stress-dimension relations in human subjects appear to be linear and are sensitive to the inotropic state.     

"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.     

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.     

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.