Progress in computer analysis of the exercise electrocardiogram

The potential advantages of digital computer processing of exercise electrocardiographic data include reduction of noise, compression of data, improved precision and application of optimal criteria. Most prior approaches to such processing required equipment that was both expensive and inconvenient. With the revolution in instrumentation brought about by the development of microcomputers, powerful dedicated computers can now be afforded by many exercise laboratories. There are many approaches to computerized management of exercise electrocardiographic data and various criteria for ischemia. Studies are necessary to validate computer algorithms so that these devices can be used diagnostically to best advantage. Cardiologists need some understanding of this field so that they can be discriminating users of computer systems. In addition, the results of studies correlating electrocardiographic changes with radionuclide methods of assessing myocardial perfusion and function should enable such assessments to be made from the electrocardiographic signals alone, particularly when aided by computer analysis of spatial shifts.     

Exercise testing and training: clinical applications

The application of exercise in clinical cardiology continues to progress because of research findings. Advances have occurred in the applications, methodology and interpretation of exercise testing. Exercise training has been documented to have a place in the primary prevention of coronary heart disease. In regard to cardiac rehabilitation, both early ambulation and early discharge are safe and beneficial in patients with uncomplicated infarction, and a subsequent exercise program is at least as effective as other interventions. High intensity exercise training in the patient with heart disease may be necessary to cause changes in myocardial perfusion and performance, but it carries an increased risk.     

Variations in normal electrocardiographic response to treadmill testing

Forty healthy young men at low risk for coronary artery disease underwent progressive maximal treadmill testing. Four bipolar electrocardiographic leads including CM₅, CC₅, inferior-superior Y, anterior-posterior Z, and a standard V₅ were recorded and later computer-processed. Measurements included amplitudes of the Q, R, S, J junction and T wave, R-T and Q-S intervals and S-T segment slope. These variables are presented as the 10th, 50th (median) and 90th percentiles throughout the testing procedure to define reference values for the electrocardiographic response to maximal treadmill testing. The medians are presented graphically so that the exercise-induced changes can be visualized. In addition, the percent change of R wave amplitude in V₅ compared with the supine pretest value is displayed for each subject during and after testing.     

Assessment of right ventricular function at rest and during exercise in patients with coronary heart disease: A new approach using equilibrium radionuclide angiography

To evaluate a new method of calculating right ventricular ejection fraction by equilibrium radionuclide angiography and to assess its response during supine bicycle exercise, 20 normal persons and 50 patients with angiographically documented coronary artery disease were studied. Each subject underwent a resting equilibrium and first pass right ventricular study as well as symptom-limited graded bicycle exercise while supine. The correlation between the two methods in all 70 cases was good (r = 0.81). Inter- and intraobserver variability was small (3.9 ejection fraction units or less) and serial reproducibility (two studies performed 2 weeks apart) was also good (4 ejection fraction units or less). There was no difference in the right ventricular ejection fraction at rest when normal subjects and patients with coronary disease were compared (0.49 ± 0.10 versus 0.46 ± 0.08). Ejection fraction increased with exercise in normal subjects (0.49 ± 0.10 to 0.64 ± 0.12, p < 0.005). As a group, patients with right coronary stenosis (alone or in combination with other lesions) showed no change in ejection fraction with exercise (0.46 ± 0.13 to 0.45 ± 0.12); and ejection fraction increased with exercise in patients with coronary disease without right coronary stenosis (0.46 ± 0.08 to 0.53 ± 0.11, p < 0.05). Among patients with both significant right and left coronary artery disease more severe right ventricular dysfunction during exercise was seen in the presence of more severe left ventricular dysfunction. It is concluded that during exercise the right ventricle shows dysfunction caused in part by local ischemia as well as by altered loading conditions due to left ventricular dysfunction. Equilibrium angiography is a useful and reliable method for evaluating right ventricular function in man.     

Effect of sublingual nitroglycerin on left ventricular function at rest and during spontaneous angina pectoris: Assessment with a radionuclide approach

Left ventricular function and size were assessed with equilibrium radionuclide angiography at rest and after administration of 0.6 mg of sublingual nitroglycerin in 12 patients with a history of previous myocardial infarction. Spontaneous angina developed in five patients and seven patients had no pain at the time of study. Sequential ejection fractions and end-diastolic and end-systolic volumes were developed by summing multiple R-R intervals to produce a composite time-activity curve. Volumes were calculated with a nongeometric method that utilizes counts at end-diastole and end-systole and is corrected for total heartbeats and plasma radioactivity. In the patients without acute ischemia, peak increase in ejection fraction occurred 6 to 8 minutes after ingestion of nitroglycerin and was associated with an equal decrease in end-diastolic and end-systolic volumes with no change in stroke volume. End-diastolic and end-systolic volumes, stroke volume, heart rate and systolic blood pressure all returned to baseline levels by 1 hour after nitroglycerin. In the patients with spontaneous angina, ejection fraction and stroke volume decreased before pain occurred. End-diastolic volume increased slightly (7 percent), but end-systolic volume increased markedly (38 percent), thus explaining the decrease in stroke volume. After nitroglycerin, end-diastolic volume and end-systolic volume and systolic blood pressure decreased and stroke volume and ejection fraction increased. Improvement in function occurred before relief of pain.

It is concluded that the action of nitroglycerin on the left ventricle in patients without acute ischemia is to increase ejection fraction by an equal decrease in end-diastolic and end-systolic volumes with little change in stroke volume. A reduction in left ventricular function during acute ischemia precedes complaints of pain and is associated with an increase in end-systolic and end-diastolic volumes and a decrease in ejection fraction and stroke volume. In these patients, nitroglycerin appeared to contribute to relief of pain by decreasing end-diastolic volume and systolic blood pressure.     

Effect of nitrates on left ventricular size and function during exercise: Comparison of sublingual nitroglycerin and nitroglycerin paste

To compare the effects of sublingual nitroglycerin and nitroglycerin paste on left ventricular size and performance during supine bicycle exercise, equilibrium radionuclide angiography was performed in 36 persons classified into two groups of normal subjects and two groups of patients with angiographically proved coronary heart disease. Each group underwent a control exercise study, and then one group of normal subjects and one group of patients were restudied after the administration of 0.6 mg of nitroglycerin or 2 inches (5 cm) of nitroglycerin paste (but not both). Data were collected at rest and at peak exercise.In normal subjects exercise resulted in increased ejection fraction, decreased end-systolic volume and little change in end-diastolic volume. After either drug, volumes at rest markedly decreased, and during exercise, ejection fraction increased to levels comparable with pre-drug levels. After nitroglycerin paste the reduction in volume seen at rest persisted during exercise, but after sublingual nitroglycerin end-diastolic volume increased during exercise (88 ± 43 to 113 ± 30 ml [mean ± standard deviation]; p < 0.01). Peak exercise end-diastolic volume after nitroglycerin was still lower than that before nitroglycerin (113 ± 30 versus 120 ± 28 ml, p < 0.05).In patients with coronary disease, ejection fraction did not change during exercise, but both end-diastolic and end-systolic volumes increased. After either drug ejection fraction at rest was unchanged, although ventricular volumes were markedly lower (p < 0.05). Ejection fraction increased with exercise in both groups with coronary disease after either drug. After sublingual nitroglycerin, volumes increased during exercise although the peak exercise end-diastolic volume was still lower than the control value (113 ± 31 versus 145 ± 34 ml; p < 0.01). After paste administration, end-diastolic volume did not change during exercise, and end-systolic volume decreased (41 ± 20 to 36 ± 22 ml; p < 0.05).Thus, sublingual nitroglycerin and nitroglycerin paste improved left ventricular function during exercise. The effect of paste on end-diastolic volume appeared sustained, whereas that of sublingual nitroglycerin was transient, confirming the hypothesis that reduction in end-diastolic volume and, by implication, left ventricular wall tension, is a major mechanism of nitrate action.     

Assessment of early ventricular systole by first pass radionuclide angiography: useful method for detection of left ventricular dysfunction at rest in patients with coronary artery disease.

To identify abnormal left ventricular function without exercise stress in patients with coronary artery disease first-pass radionuclide angiograms were analyzed in 32 normal subjects (Group I); 31 patients with coronary disease and normal contrast ventriculograms (Group II); and 17 patients with coronary disease and depressed left ventricular function (Group III). Total ejection fraction (EF) was computed with standard angiographic methods and from each time-activity curve. During the first third of systole, ejection fraction was determined manually by averaging three to five beats and the value compared with that obtained with contrast ventriculography: (Formula: see text). Both total radionuclide ejection fraction (r = 0.95) and first-third ejection fraction (r = 0.91) correlated well with angiography. Intraobserver and interobserver variation was small, averaging 0.02 +/- 0.02 (range 0 to 0.05). The radionuclide first-third ejection fraction was 0.25 or greater in normal subjects and less than 0.25 in 29 of 31 patients (94 percent) in Group II and in all patients in Group III. It is concluded that the first-third ejection fraction obtained with first pass angiography identifies subtle abnormalities of left ventricular function at rest in more than 90 percent of patients with coronary disease that may not be recognized by total ejection fraction alone.     

Peak systolic blood pressure/end-systolic volume ratio: Assessment at rest and during exercise in normal subjects and patients with coronary heart disease

To assess the utility of a recently proposed index of left ventricular performance, the ratio of peak left ventricular systolic pressure to end-systolic volume, equilibrium radionuclide angiography was used to determine end-systolic volume and the systolic blood pressure obtained by cuff sphygmomanometer to determine peak systolic pressure. Data were analyzed at rest and during supine bicycle exercise in 15 normal subjects (Group 1), 50 patients with coronary artery disease (Group II) and 9 patients with obstructive lung disease and no evidence of coronary artery disease on clinical examination including exercise thallium imaging (Group III). In 15 subjects the correlation between the resting angiographic and radionuclide pressure/volume ratio was excellent (r = 0.929, p <0.005).Forty-seven (94 percent) of the 50 patients in Group II had a depressed pressure/volume ratio at rest or an abnormal change in this ratio during exercise, whereas only 43 (86 percent) of this group had an abnormal ejection fraction at rest or during exercise. Additionally, 3 of 15 subjects in Group I had an abnormal ejection fraction response, defined as less than 0.05 ejection fraction unit increase with exercise (specificity 80 percent), whereas all subjects in Group I had a normal increase in pressure/volume ratio (specificity 100 percent). At rest, neither index identified more patients with coronary artery disease than the other. Of the nine patients in Group III, six had an abnormal ejection fraction response to exercise, whereas only one had an abnormal pressure/volume ratio response.It is concluded that the end-systolic pressure/volume ratio is a useful index of left ventricular performance. In some patients during supine exercise stress it may be more sensitive than the ejection fraction response alone in identifying the presence of coronary artery disease.     

Comparison of digital intravenous ventriculography with direct left ventriculography for quantitation of left ventricular volumes and ejection fractions

Digital images of the left ventricle obtained at 30 frames/second from continuous fluoroscopy after intravenous injection of contrast medium (digital intravenous Ventriculography) were used to estimate left ventricular (LV) volumes and ejection fraction with use of several techniques for identifying the ventriculographic silhouette. The digital technique was compared with direct contrast left Ventriculography in 26 patients undergoing diagnostic cardiac catheterization. End-diastolic and end-systolic volumes calculated from digital intravenous and direct left ventriculograms were obtained with use of a standard area-length formula. Both end-diastolic volume (EDV) (r = 0.88, y = 1.06x ? 17.1 ml) and end-systolic volume (ESV) (r = 0.89, y = 0.96x + 0.43 ml) determined from digital intravenous ventriculography (mask mode images) correlated closely with those obtained by direct left ventriculography. Combining the EDV and ESV to define the relation between the 2 techniques yielded an even closer correlation (r = 0.96). There was also good correlation between the 2 techniques for measurement of ejection fraction (r = 0.81, standard error of the estimate 6.7%). Measurements from direct left Ventriculography were frequently invalidated by ventricular arrhythmias during the time of opacification of the left ventricle; this was rarely the case for digital intravenous Ventriculography. It is concluded that area-length estimates of LV volumes and ejection fraction can be accurately obtained from digital processing of fluoroscopic LV images after intravenous injection of contrast medium.     

Serial noninvasive assessment of left ventricular hypertrophy and function after surgical correction of aortic regurgitation.

Serial echocardiographic analyses of left ventricular hypertrophy and function, with validation of extent of shortening by first pass radionuclide angiography, was performed in 16 patients before and after surgical correction of severe aortic valve regurgitation. All patients were symptomatic (predominantly in New York Heart Association functional class III or IV) before operation but were in class I or II after operation. The preoperative pattern of eccentric hypertrophy (increased mass with normal ratio of left ventricular cross-sectional wall area to cavity area) changed immediately after operation to a pattern of concentric hypertrophy (increased mass with increased ratio of left ventricular cross-sectional wall area to cavity area) because of a significant reduction in chamber size and increase in wall thickness. On late follow-up (9 to 35 months, average 15 months after operation), the hypertrophy lessened significantly, the cross-sectional area of the ventricular wall decreasing to 21.1 ± 5.4 (mean ± standard deviation) cm² from a preoperative average of 31.6 ± 4.8 cm² (P < 0.01), and the ratio of wall area to cavity area was once again normal. In the same period, left ventricular enddiastolic diameter decreased from 6.52 ± 0.68 to 4.64 ± 0.52 cm (P < 0.01). Preoperatively, ejection phase indexes were normal or only marginally depressed in 12 of 16 patients but were moderately depressed in the remaining 4. At early follow-up (average 4 months) ventricular shortening tended to increase; and at late follow-up the fractional shortening of the minor axis, the ejection fraction and the mean velocity of circumferential fiber shortening increased to 0.39 ± 0.07, 0.68 ± 0.10 and 1.26 ± 0.22 circumference/sec, respectively, from preoperative values of 0.33 ± 0.09, 0.60 ± 0.14 and 1.05 ± 0.31 circumferences/sec (P < 0.05 for each index). In the four subjects with preoperative depression of left ventricular function, the extent and speed of myocardial shortening at late follow-up became normal in three subjects and remained moderately depressed in one patient. Paradoxical septal motion was observed immediately postoperatively and in the early follow-up studies, but it was noted in only 3 of 16 cases by the late follow-up period. Provided septal dyskinesia was not present, echocardiographic and first pass radionuclide determinations of ejection fraction correlated highly (r = 0.92).It is concluded that when aortic valve replacement for symptomatic aortic regurgitation is undertaken prior to severe myocardial decompensation, improvement in clinical status is associated with significant regression of myocardial hypertrophy, reduction in left ventricular size, evolution of a normal $\text{mass}\text{volume}$ ratio, recovery of septal dyskinesia as revealed on echocardiography, and improvement in left ventricular function. These data do not define the type and degree of left ventricular dysfunction which is irreversible.     

Ultrasonic enhancement of myocardial infarction with perfluorocarbon compounds in dogs

Medically pure (100%) carbon dioxide directly injected into a peripheral vein was used for 2-dimensional contrast echocardiography in 134 patients with an arteriovenous shunt demonstrated by cardiac catheterization and cineangiography, Qp/Qs ratios of 1.5 to 3.7, pulmonary-to-systemic peak systolic pressure ratios of 0.2 to 0.8 and no oximetrically demonstrable venoarterial shunt. Two patients with transposition of the great arteries, intact ventricular septum and a Senning operation as well as 30 normal subjects of comparable age also were studied. In patients with an atrial septal defect, the gas microbubbles opacified the left atrium. In patients with a ventricular septal defect, the gas microbubbles opacified the left ventricle, whereas the left atrium was free of contrast. In all patients with patent ductus arteriosus, the gas microbubbles opacified the abdominal aorta, whereas the left atrium, left ventricle, aortic root and aortic arch remained free of contrast. In 2 patients in whom an aneurysm of the sinus of Valsalva ruptured into the right ventricle, the "negative" contrast effect permitted localization of the shunt. In 2 patients with transposition of the great arteries, an intact ventricular septum and a Senning operation, the intracardiac flow pattern was clearly demonstrated. No complication was observed. We conclude that pure carbon dioxide directly injected into a peripheral vein is a safe and advantageous echocardiographic contrast material. Because of its greater diffusibility in comparison with oxygen and fluid contrast media, small venoarterial shunting can be detected in defects such as atrial septal defect, ventricular septal defect and patent ductus arteriosus, in which only an arteriovenous shunt can be demonstrated by oximetry.     

Assessment of mitral valve E point-septal separation as an index of left ventricular performance in patients with acute and previous myocardial infarction

A new echocardiographic index of left ventricular function, mitral valve E point-septal separation, was compared with the radionuclide ejection fraction determined using the first pass method in 60 patients (73 studies) with ischemic heart disease. Thirty-eight patients had acute myocardial infarction and 22 patients were studied an average of 24 months after acute infarction. In 30 normal subjects, E point-septal separation ranged from 0 to 5.4 mm (average 1.3 mm). In 57 studies (78 percent) E point-septal separation correctly identified patients with a normal or reduced ejection fraction (less than 0.52), but in 13 studies (18 percent) E point-septal separation was normal and ejection fraction depressed. In only three studies (4 percent) was there a normal ejection fraction and an abnormal E point-septal separation. Results did not differ between patients with acute infarction and those studied late after infarction. An E point-septal separation of more than 5.5 mm was highly specific (92 percent) for a reduced ejection fraction, but the sensitivity rate was only 65 percent. Abnormal wall motion as assessed with echocardiography or videotracking, or both, occurred equally among patients with normal and increased E point-septal separation, but this measure was less accurate in patients with more severe wall motion abnormalities. E point-septal separation was unrelated to heart rate; an abnormal value was equally distributed among patients with a normal and those with an enlarged left ventricular end-diastolic dimension on echocardiography. E point-septal separation was superior to other echocardiographic indexes of left ventricular function (percent of fractional shortening, mean rate of diameter shortening and ejection fraction). Thus, E point-septal separation is a simple noninvasive measure of left ventricular function. We conclude that an abnormal E point-septal separation is useful for identifying depressed left ventricular function in patients with acute myocardial infarction and chronic ischemic heart disease. However, 28 percent of our patients with a normal E point-septal separation had a depressed radionuclide ejection fraction. Therefore a normal value for E point-septal separation does not exclude the presence of abnormal left ventricular function in such patients.     

Beneficial effects of nitroglycerin on abnormal ventricular wall motion at rest and during exercise in patient with previous myocardial infarction.

The effects of sublingually administered nitroglycerin on segmental left ventricular wall motion determined by videotracking and radiographic left heart size were evaluated at rest and during submaximal hand grip exercise in 10 patients with previous transmural myocardial infarction. After nitroglycerin, diastolic left heart size decreased in the resting state from an average of 49.5 +/- 5.7 (standard deviation) to 47.9 +/- 5.6 mm/m2 body surface area (P less than 0.01) and during handgrip exercise from a mean of 50.7 +/- 590 to 49.1 +/- 4.7 mm/m2 (P less than 0.05). In the resting state, the average maximal velocity of shortening in segments with normal wall motion increased after nitroglycerin from 18.1 +/- 3.0 to 23.5 +/- 5.5 mm/sec (P less than 0.01), whereas during handgrip exercise alone, the velocity of shortening averaged 25.6 +/- 6.9 mm/sec and increased further after nitroglycerin to 30.1 +/- 10.6 mm/sec (P less than 0.05). The effects of nitroglycerin on the average extent of shortening in normal segments were similar. In all 10 patients, there was a decrease in the number of segments with abnormal wall motion. The number of sites with dyssynergy decreased after nitroglycerin from 24 to 15 in the resting state and from 40 to 22 when nitroglycerin was administered before handgrip exercise. Sublingually administered nitroglycerin appears to decrease left heart size, increase the velocity and extent of shortening in normal left ventricular segments and often reduce the extent of left ventricular wall motion abnormalities at rest and during isometric exercise in patients with previous transmural myocardial infarction.