Enhanced risk assessment for primary coronary heart disease events by maximal exercise testing: 10 years' experience of Seattle Heart Watch.

A 10 year prospective community practice study in Seattle of risk of primary morbidity (defined by hospital admission) and mortality due to coronary heart disease in 3,611 men and 547 women initially free of clinical manifestations of this disease revealed a crude incidence of 202 coronary heart disease events, or 4.9% in 6.1 +/- 2.6 years of follow-up. The case fatality rate was 16.8%. Stratification by clinical classification of asymptomatic healthy persons versus patients with atypical chest pain syndrome (not angina pectoris) and hypertension (as classified by physicians) showed an incidence rate of primary events due to coronary heart disease of 2.9, 5.5 (not significant) and 10.0% (p less than 0.001), respectively. Identification of conventional risk factors is known to be important for risk assessment. However, the presence of any conventional risk factor, in conjunction with two or more selected maximal exercise predictors (which vary with the clinical classification) at enrollment, substantially increased the cumulative 6 year incidence rate to 24.3, 15.5 and 33.3% in asymptomatic healthy men, patients with atypical chest pain syndrome and hypertensive patients, respectively. Observation of the exercise predictors in the absence of conventional risk factors increased the risk much less, suggesting that the use of maximal exercise testing for risk assessment in those with no clinical manifestations of disease might be limited to persons with one or more conventional risk factors.

Validation of exercise-enhanced risk assessment of coronary heart disease events: longitudinal changes in incidence in Seattle community practice.

Noninvasive criteria developed in a learning series for exercise-enhanced risk assessment for events due to coronary heart disease have been applied to a test series in a later population sample. Men in the same age and risk groups for each pretest clinical classification show similar gradients of risk. Thus, exercise-enhanced criteria for risk assessment are validated. Age-standardized event rates show a reduction longitudinally in healthy men and patients who have had coronary bypass surgery.

Changes in cardiac functional capacity after coronary bypass surgery in relation to adequacy of revascularization.

Seventy patients having aortocoronary vein bypass grafting surgery for angina pectoris underwent preoperative invasive exercise testing to symptom limits and again 6 to 14 months postoperatively. Cardiac output was measured using the direct Fick principle. Postoperatively at maximal exercise, there was a 3.11 liters/min (p less than 0.0001) increase in cardiac output in men (n = 61) and a 2.04 liters/min (p less than 0.01) increase in women (n = 9). Patients with complete revascularization showed a significantly greater improvement in cardiac output postoperatively than did those with incomplete revascularization (26 versus 6%, p less than 0.0001). The major reason for the increased maximal cardiac output was a marked increase in heart rate while stroke volume was maintained at the same preoperative level. These findings were true irrespective of preoperative use of beta-adrenergic blocking drugs.

Health benefits of exercise in an aging society.

The effects of regular aerobic exercise are important to an aging society increasingly preoccupied with exercise. Traditionally, most attention has been directed to the relationship between a physically active life-style and cardiovascular mortality. In an aging society, however, active life expectancy and maintenance of independence may be as important as effects of regular exercise on longevity. Regular exercise results in increased maximum aerobic capacity due to peripheral changes in muscle (increased capacity for aerobic metabolism and improved substrate and oxygen extraction with a widened arteriovenous oxygen difference) and also due to cardiovascular changes with increased stroke volume and cardiac output in normal persons. "Therapeutic benefits" of conditioning probably occur at submaximal work loads common to everyday activity, when cardiac work and myocardial oxygen consumption are less for any given work load, muscles are more efficient, and relative oxygen requirements are less. Aging is associated with a linear decline in maximum aerobic capacity. The rate of decline is twofold greater when comparing sedentary with physically active middle-aged men. Thus, regular exercise could conceivably lower functional aerobic age by slowing this functional decline. Exercise, particularly excessive exercise, is also associated with serious hazards, including sudden death, nonfatal myocardial infarction, excessive fatigue, hyperthermia, and significant musculoskeletal problems. Accounts of the health effects of exercise should consider a wide range of risks and benefits, especially those related to improving function, minimizing disability, and prolonging independent living.

Exertional hypotension and postexertional ventricular fibrillation in stress testing.

Six men, clinically diagnosed as having coronary heart disease, had postexertional ventricular fibrillation after maximal exercise testing. The common featureof their treadmill performance was "exertional hypotension," that is, a decrease or a limited increase (10 mm Hg) in systolic blood pressure. All six men were successfully resuscitated with electircal defibrillation. The major indication for electrocardiographic monitoring is the detection of major ventricular arrhythmias and changes in QRS-ST-T of acute myocardial infarction or severe ischemia, all of which are urgent indications for stopping exertion. Close supervision both during and after exercise testing is essential, particularly in men with severe coronary artery disease; monitoring of changes in systolic pressure during and shortly after exercise testing is as important as searching for changes in the -S-T segment.

Improved exercise performance in persons with stable angina pectoris receiving diltiazem.

The effects of diltiazem, a calcium antagonist drug, we compared with those of placebo on exercise performance during a series of symptom-limited upright exercise tests. Ten patients with chronic stable angina were studied over a period of 7 weeks. The drug was administered in a random double-blind fashion and was evaluated at increasing dose levels of 120, 180 and 240 mg/day. Diltiazem was effective in increasing the total duration of exercise (p < 0.001) and the time the first onset of angina (p < 0.02) and to the first appearance of 1 mm of S-T depression (p < 0.02). These effects were most marked at the highest dose level of diltiazem. The heart rate was reduced at rest (p < 0.05) and during submaximal exercise (p < 0.001). There was a reduction in diastolic blood pressure during submaximal exercise (p < 0.04) but no change in systolic pressure. Pressure-rate product was significantly reduced at submaximal (p < 0.001) but not maximal exercise. The reduction in pressure-rate product is postulated as the mechanism by which diltiazem enhances duration of exercise. There was no reduction in electrocardiographic evidence of myocardial ischemia at peak exercise by either clinical observation or computer analysis of spatial electrocardiographic variables Five of the six patients who continued to take the drug maintained or improved their exercise performance on follow-up study 8 to 10 months later.

Differences in cardiac function with prolonged physical training for cardiac rehabilitation.

Ten men aged 40 to 68 years with clinical manifestations of cardiovascular disease and who had participated for 2 to 59 months in a physical training program for cardiac rehabilitation were studied. All 10 underwent measurements of maximal oxygen uptake and invasive studies of cardiac output, using the direct Fick method, at rest and at graded levels of exercise in the upright posture. Of four men who left the training program, three continued activities individually. Physiologic measurements were repeated after a lapse of 13 to 38 months (average 23 months). The rate of change in maximal oxygen uptake relative to normal changes with aging was decelerated in four men over an average of 21.8 months and was accelerated in six men over an average of 23.2 months. At comparable oxygen requirements of exercise, stroke volume and cardiac output were unchanged in the former group but significantly decreased in the latter. Arterial oxygen content and arteriovenous oxygen difference increased in both groups. These results show that prolonged physical training results in physiologic adaptations of cardiac rehabilitation even though deterioration of cardiac function with advancing disease is probable in some patients.

Approximate normal standards of maximal cardiac output during upright exercise in women.

The observed normal ranges of age- and weight-adjusted maximal oxygen uptake and age-adjusted maximal heart rate during upright exercise using the Bruce protocol are shown for 104 asymptomatic women. Cardiac output was measured during upright exercise in 11 normal women with the use of the direct Fick method. On the basis of the relation between oxygen uptake and cardiac output in these 11 women, the cardiac output and stroke volume were estimated by regression in the 104 women to provide normal ranges of age-adjusted values for cardiac output and stroke volume. The potential usefulness of these age-adjusted normal ranges is illustrated by analysis of 21 observations of maximal cardiac output in 16 women with heart disease.

Estimation of inferobasal myocardial infarct size by late activation abnormalities of the QRS complex.

This report describes the relation of myocardial infarct (MI) size in the left ventricular inferobasal wall, measured at necropsy, to late activation abnormalities of the QRS complex, measured by computerized spatial vectorcardiography. Fifteen patients with single inferobasal MIs and 10 patients with no evidence of heart disease were studied. The percentage of MI in the inferobasal wall was significantly related to the vectorcardiographic abnormalities noted late (i.e., 31 +/- 13 ms before the end of the QRS waveform) (r = 0.96, p less than 0.00001). The integral of the vector magnitudes during late abnormal activation significantly predicted the amount of MI in the basal inferior wall (r = 0.88) and in the basal inferior wall plus the outer, subepicardial half of the transmural middle inferior, lateral and inferoseptal walls (r = 0.91). The additional information obtained from late activation of the QRS complex contributed more significance to the estimation of the left ventricular inferobasal MI size than the abnormalities commonly noted during early activation (i.e., during the Q wave).

Acute effects of oral propranolol on hemodynamic responses to upright exercise.

Noninvasive measurements of maximal oxygen intake and invasive measurement of systemic and pulmonary arterial pressures, arterial and mixed venous oxygen contents and direct Fick cardiac output are reported for 3 healthy men and 14 men with coronary heart disease. Observations were obtained at supine and sitting rest, during graded levels of upright exercise on a treadmill up to symptom-limited maximal effort and in two periods of recovery. The effects of 40 mg of propranolol orally were ascertained by repeating the measurements 1 to 1 1/2 hours later. The most consistent effect of propranolol was reduction of pressure-rate products at all phases; slowing of heart rate was significant only during exercise and recovery, and the greater slowing was accompanied by a significant increase in stroke volume. These changes were similar in patients with and without evidence of left ventricular impairment greater than 15 percent on exercise testing. Maximal oxygen intake decreased in healthy subjects and decreased slightly in patients with coronary heart disease with less than 15 percent left ventricular impairment or percent deviation of pressure-rate product from age-predicted normal values during the control study. Maximal oxygen intake increased in patients with more than 15 percent left ventricular impairment. Arterial-mixed venous oxygen difference increased after propranolol because of a reduction of mixed-venous oxygen content attributed to greater peripheral extraction of oxygen.

Variations in and significance of systolic pressure during maximal exercise (treadmill) testing.

Variations in clinical noninvasive systolic pressure at the point of symptom-limited exercise on a treadmill were examined in six groups of subjects: 5,459 men and 749 women classified into three categories each. Among the men, 2,532 were asymptomatic healthy, 592 were hypertensive and 1,586 had clinical manifestations of coronary heart disease (that is, typical angina pectoris, prior myocardial infarction or sudden cardiac arrest with resuscitation). Among the women, 244, 158 and 347 were in the corresponding clinical categories. None had had cardiac surgery; all had follow-up status ascertained by periodic mail questionnaires. Reported deaths were reviewed and classified by three cardiologists; 140 deaths were attributed to coronary heart disease, 118 of them in the men classified as having coronary heart disease. The majority of maximal systolic blood pressure readings were reported to the nearest centimeter rather than millimeter of pressure. Retesting of 156 persons from 1 to 32 months later showed that pressure values agreed within 10 percent in two thirds, the overall mean difference was only 8.6 mm Hg and the correlation at maximal exercise was superior to that of the resting observations just before exercise. Hypertensive patients had a significantly greater body weight than normotensive persons. Among men, the lowest maximal systolic pressure was observed in the group with coronary heart disease; among women, the lowest mean pressure was found in the healthy group. Patients with coronary heart disease were slightly older, and only the women showed a significant correlation in maximal pressure with age. Only 5 percent of the variation in maximal systolic pressure in the patients with coronary heart disease was due to a shortened duration of exercise. Maximal systolic pressures correlated fairly well (r equals 0.46 to 0.68 for the various groups) with resting systolic pressure, and this relation was independent of the diagnosis of cardiovascular disease in both men and women. Relations between pressure and the number of stenotic coronary arteries and imparied ejection fraction at rest were examined in 22 men without and 182 men with coronary artery disease. Lower maximal systolic pressures were often associated with two or three vessel disease or reduced ejection fraction, or both. The prognostic value of maximal systolic pressure for subsequent death due to coronary heart disease was examined in the men with coronary heart disease. The annual rate of sudden cardiac death decreased from 97.9 per 1,000 men to 25.3 and 6.6 per 1,000 men as the range of maximal systolic pressure increased from less than 140 to 140 to 199 and to 200 mm Hg or more, respectively. Cardiomegaly, Q waves in the resting electrocardiogram and persistent postexertional S-T depression were more common in men with the lowest systolic pressure at maximal exercise.

Validation of a computerized QRS criterion for estimating myocardial infarction size and correlation with quantitative morphologic measurements.

This replication study describes the relation of myocardial infarction (MI) size, measured at autopsy, to initial and late QRS abnormalities, measured by computerized spatial vectorcardiography. Thirty-one patients with MIs of differing ages and left ventricular locations and 24 patients with no evidence of heart disease were studied. The percent volume of MI was significantly estimated by the initial QRS abnormalities (r = 0.94, p less than 0.00001). The 2 regression equations from the previous training set and from this present test set were compared to verify validity of the criterion, the integral of magnitudes of spatial vectors during initial abnormal depolarization to estimate MI size. There was not a significant difference between the 2 intercepts, the 2 slopes, the 2 straight-line regressions or the 2 correlation coefficients. The additional information obtained from late QRS abnormalities contributed little to improve estimation of size of multiple MIs of differing ages and left ventricular locations, but accurately predicted (r = 0.87) the size in single inferobasal MI. The results indicate that vectorcardiographic measurements of early activation abnormalities is a valid criterion to estimate MI size.

Prediction of maximal cardiac output in preoperative patients with coronary artery disease.

Of 100 patients (89 men, 11 women) studied preoperatively to determine their aerobic and hemodynamic profiles at rest and during upright treadmill exercise. The mean maximal cardiac output (CO), measured using the direct Fick principle, was 57 +/- 14% of average normal values. The reduction in maximal heart rate (63 +/- 13% of normal) was a greater factor in the reduction in CO than stroke volume (88 +/- 16% of normal). Maximal oxygen consumption (VO2max) was 48 +/- 15% of normal and the greater reduction in VO2max compared with CO was due to lower peripheral extraction in the coronary patients. Variables that correlated with maximal CO in a univariate analysis included angina severity (r = -0.45), VO2max (r = 0.67), maximal heart rate (r = -0.31), left ventricular dysfunction (r = -0.45), maximal systolic blood pressure (r = -0.31) and number of vessels with greater than or equal to 50% diameter reduction (r = -0.3). Resting ejection fraction did not correlate with maximal CO. In a multivariate analysis, 4 variables correlated significantly (r = 0.77) with maximal CO: in order, VO2max, number of vessels with greater than or equal to 50% stenosis, magnitude of ST depression and sex.

Comparison of active participants and dropouts in CAPRI cardiopulmonary rehabilitation programs.

Of 547 men and 56 women enrolled up to April 1974 in Cardiopulmonary Research Institute (CAPRI) community programs for cardiopulmonary rehabilitatation, 84.5 percent had clinical manifestations of coronary heart disease. These medically supervised programs of physical training involved 30 to 60 minutes of graded levels of working, calisthenics and, if indicated, jogging for 3 mornings/week. Altogether 352 (58.4 percent) dropped out after an average of 8.6 months for men and 5.7 months for women. The remaining 230 men and 21 women remained active for 22 and 20 months, respectively. In retrospect, there were few minor differences between active participants and dropouts in physical characteristics, clinical diagnoses and responses to exercise testing on enrollment. Elapsed time to morbidity tended to be longer in active persons than in dropouts. Over one half of active men and about one third of dropouts were working. Of six early deaths, one occurred before training was instituted, and five within the first 2 weeks of training. Among men, the respective total mortality rates were 2.7 and 4.7/100 person-years for active participants and dropouts; among women, the rates were 0 and 3.8 respectively. Whereas 24 episodes of cardiac arrest occurred in 13 men, with three fatalities outside the training program, in 11 instances of exertional arrest during class training all defibrillations were successful. Without this benefit of medical supervision there would have been little difference in mortality experience.

Noninvasive predictors of sudden cardiac death in men with coronary heart disease. Predictive value of maximal stress testing.

In a follow-up study of 1,852 men with coronary heart disease, 195 deaths occurred within the first 3 years (33 +/- 13 months [mean +/- standard deviation]). Analysis of these cases indicated that the risk of sudden cardiac death in ambulatory men with clinical manifestations of coronary heart disease may be readily estimated from noninvasive clinical and exercise criteria. The important predictors are indexes of the severity of coronary heart disease and impairment of peak left ventricular function demonstrated with symptom-limited maximal exercise. The advantages of these predictors are that they may be elicited on the initial study as well as on follow-up noninvasive examinations of ambulatory patients. The appearance of nonelectrocardiographic predictors in serial examinations may provide an indication for invasive studies and be a more important finding than the ischemic S-T reponse to exertion.

Improvement in aerobic and hemodynamic responses to exercise following aorta-coronary bypass grafting.

Preoperative and postoperative hemodynamic studies were performed during exercise in 70 patients having aorta-coronary bypass grafting for the treatment of angina. There was significant symptomatic improvement with 88% of patients free of angina postoperatively. In patients with complete revascularization there was a marked improvement during exercise in maximal oxygen consumption, cardiac index, and maximal pressure-rate product. In addition, there was a fall in pulmonary arterial pressure postoperatively. In contrast, patients with incomplete revascularization showed a small but insignificant rise in maximal oxygen consumption and cardiac index. The major reason for the increase in cardiac index was a marked increase in heart rate rather than a change in stroke index. In patients with complete revascularization there was a significant increase in stroke work index at maximal exercise.

Chemotherapy for treatment of choroidal metastases from breast carcinoma.

Of 15 patients with choroidal metastases from breast carcinoma, eight were treated with radiation therapy and six with chemotherapy. One patient received both. Although five of the six patients receiving chemotherapy died after an average follow-up period of 12 months, these patients generally had more widespread disease and a worse prognosis originally. Chemotherapy proved to be as effective as radiation therapy for this tumor.

Exercise, functional aerobic capacity, and aging--another viewpoint.

Currently, there is strong public interest in exercise conditioning, especially endurance types of dynamic exercise. In addition to the short-term benefits of enhanced fitness and health, there is a growing expectation of long-term benefits in relation to possible reduction of morbidity, disability, and mortality from chronic disease, especially cardiovascular disease. Physical exercise increases aerobic metabolism and the associated pulmonary and cardiovascular responses needed to deliver the required oxygen. Functional aerobic capacity or maximal oxygen consumption (VO2max) defines the functional limits of the cardiovascular system. Aerobic capacity can be measured or be reasonably estimated by appropriate methods of exercise testing, and is probably the best integrated measure of the functional limits of the whole body which can define the effects of the aging process. The rate of decline in VO2max observed in longitudinal studies of the same subjects substantially exceeds that observed in cross-sectional studies sampling male subjects of different ages. This rate is twice as great in sedentary as in physically active male subjects. When these provocative findings are considered in relation to trends observed in survival of populations vs the nearly constant limit of the average life span, the need for appropriately designed long-term prospective, definitive studies becomes apparent.

Relationships of working status and cardiac capacity to functional age before and after coronary bypass surgery.

In 77 patients having coronary bypass surgery, we evaluated the interaction between chronological age, functional age, and working status pre- and postoperatively. Preoperatively the chronological age of those not working compared to those working was 60.7 +/- 8.4 years versus 53.0 +/- 8.3 years (P less than 0.001). The preoperative functional ages were 93.5 +/- 11.5 versus 87.6 +/- 10.9 years (P less than 0.05). Postoperatively no patient who was not working preoperatively started work, although functional age improved from 93.5 +/- 11.5 to 83.2 +/- 12.8 years (P less than 0.001). Postoperatively subjects who stopped working showed similar improvement in maximal cardiac output, and maximal oxygen consumption compared to those who continued working; however, the functional age after surgery was 80.6 +/- 9.4 versus 69.6 +/- 11.6 years (P less than 0.01). This study showed a poor relationship between degree of improvement in cardiac function after bypass surgery and change in working status. However, functional age and chronological age contribute to the poor results with regard to return to work.

Mean systolic ejection rate after aortocoronary bypass graft surgery.

In 62 patients with coronary artery disease who underwent aortocoronary bypass graft surgery, we measured the mean systolic ejection rate invasively at rest and during upright exercise before and several months after operation. After bypass surgery, mean systolic ejection rate did not show any change at either supine or sitting rest and at submaximal exercise levels of walking on a treadmill. At maximal exercise, only patients with complete revascularization showed a significant increase in heart rate from 105 to 147 (+40%) and mean systolic ejection rate from 339 ml/sec to 404 ml/sec (+19%, P less than 0.001). Patients with incomplete revascularization did not show a substantial change in these variables. Beta-blocker withdrawal did not affect the result significantly.