David Jensen

A Randomized Trial of Exercise Training in Patients With Coronary Heart Disease

In order to determine whether or not regular exercise could alter myocardial perfusion or function, we randomized 146 male volunteers with stable coronary heart disease to either a supervised exercise program (n = 72) or to a usual care program (n = 74). Subjects underwent exercise tests initially and one year later. Significant differences between the two groups included improved aerobic capacity, thallium ischemia scores, and ventricular function in the exercise intervention group. It was not possible to classify the conditions of patients as to the likelihood of improvement or deterioration. This study demonstrated changes in myocardial perfusion and function in a select group of middle-aged men with coronary heart disease who underwent a medically appropriate exercise program lasting one year, but these changes were relatively modest.

Agreement in human interpretation of analog thallium myocardial perfusion images.

To assess the agreement of human interpretation of analog thallium myocardial perfusion images, four experienced interpreters evaluated 100 images on two occasions using a form designed to limit reader variability. A high intraobserver agreement (agreement by same observer at separate times) of 89–93% was found when films were interpreted as normal or abnormal (a dichotomous decision). Interobserver agreement for a majority grouping of observers (three or four) was 75% for an abnormal and 68% for a normal interpretation. However, agreement ranged from 11–79% when interpreters were asked to read the anatomic location of defects. Posterior and lateral wall defects were interpreted with the least amount of agreement. These results indicate that caution must be taken when interpreting defect location. Using a scale of 1–10 to grade the severity of a defect, correlations of 0.82–0.86 were found when reading defects in the lateral and anterior projections. Higher correlations, from 0.86–0.94, were found in left anterior oblique views. Use of reporting forms with specific criteria, multiple observers at one occasion, and/or computer processing may improve agreement. A brief review of the agreement of cardiology testing procedures is also presented.

THE ANEURAL HEART OF THE HAGFISH

Because of their unique position as the most primitive living craniate vertebrates, the hagfishes (myxinoids) have excited considerable interest among biologists engaged in widely divergent areas of research. Certain information regarding these animals in relation to their natural habitat is basic to an appreciation of problems dealing with the hagfishes’ cardiovascular system. Consequently, a brief outline of certain salient features of their general biology, etc. will serve to introduce the main theme of this paper. For more extensive treatment of these animals, reference is made to a recent and comprehensive monograph on myxinoids.’ Taxonomically, hagfishes belong to the class Cyclostomata or “roundmouths,” and to the more inclusive group of Agnatha, or jawless vertebrates. I n this regard they are more advanced than the protochordates (amphioxus and tunicates), yet more primitive than either elasmobranch or teleostean fishes. Hagfishes are generally grouped with their nearest living relatives, the lampreys, but there is much evidence to support the contention that these two subgroups should be regarded as of distinct origin. About 24 species of hagfishes are recognized and are generally considered to comprise the family Myxinidae.’ Superficially resembling eels in appearance, hagfishes are elongated in body form and lack paired fins and the pectoral and pelvic girdles which normally support such structures (FIGURE 1). The skeleton is wholly cartilagenous, and without trace of ca l~ i f ica t ion ;~ the notochord persists in the adult. The internal conditions are unfavorable for the deposition of bone,‘ a point of interest in relation to the very limited osmoregulatory ability of these animalss The serum of hagfishes is approximately isoosmotic with sea water, although individual ions are regulated to a limited extent.6 The eyes are vestigial and the animals are essentially blind. About the mouth and single median nostril are grouped four pairs of fleshy barbels which serve a tactile f ~ n c t i o n . ~ Their sense of olfaction is quite keen, an important adaptation to their normal ecological situation on the ocean floor. The sexes are separate and the fertilization of the large ova is external. Unlike the lampreys, which undergo a larval stage of development, there

Improvement in ventricular function during exercise studied with radionuclide ventriculography after cardiac rehabilitation

A heterogeneous group of 19 consecutive patients with coronary artery disease were studied with radionuclide ventriculography before and after a mean of 6 months of exercise training. Ejection fraction was measured at rest, at matched submaximal supine work loads and during maximal supine bicycle exercise. After training there was no change in mean ejection fraction at rest or during maximal exercise, but a higher maximal mean systolic blood pressure, heart rate and work load were achieved. At equivalent submaximal work loads after training, similar levels of mean heart rate and systolic blood pressure were reached but a statistically greater mean ejection fraction was obtained. These preliminary results suggest that exercise training may improve cardiac function during exercise in selected patients with coronary disease. A randomized study using similar techniques has been initiated.

Can areas of myocardial ischemia be localized by the exercise electrocardiogram? A correlative study with thallium-201 scintigraphy

In order to determine whether areas of ischemia identified by thallium-201 scintigraphy could be localized by exercise ECG, we studied 54 patients with stable coronary heart disease. All 54 patients had exercise-induced thallium-201 scintigraphic defects. Their exercise ECG test results were compared to their thallium-201 images and also to 14 low-risk normal subjects. Exercise data were analyzed for spatial ST vector shifts, using a computer program in order to most accurately classify ST segment depression and elevation. Thallium-201 ischemic defects detected in our patients included areas in the septum and the inferior, lateral, and anterior walls. Twenty-six of these 54 patients also had coronary angiography for classification and comparison as having either localized or generalized disease. None of the scintigraphic ischemic sites or angiographic diseased areas could be specifically identified by exercise-induced ST vector shifts. Therefore, the surface exercise ECG has limitations in localizing ischemia to specific areas of the myocardium.

Treadmill performance and cardiac function in selected patients with coronary heart disease.

To investigate the cardiac determinants of treadmill performance in patients able to exercise to volitional fatigue, 88 patients with coronary heart disease free of angina pectoris were tested. The exercise tests included supine bicycle radionuclide ventriculography, thallium scintigraphy and treadmill testing with expired gas analysis. The number of abnormal Q wave locations, ejection fraction, end-diastolic volume, cardiac output, exercise-induced ST segment depression and thallium scar and ischemia scores were the cardiac variables considered. Rest and exercise ejection fractions were highly correlated to thallium scar score (r = -0.72 to -0.75, p less than 0.001), but not to maximal oxygen consumption (r = 0.19 to 0.25, p less than 0.05). Fifty-five percent of the variability in predicting treadmill time or estimated maximal oxygen consumption was explained by treadmill test-induced change in heart rate (39%), thallium ischemia score (12%) and cardiac output at rest (4%). The change in heart rate induced by the treadmill test explained only 27% of the variability in measured maximal oxygen consumption. Myocardial damage predicted ejection fraction at rest and the ability to increase heart rate with treadmill exercise appeared as an essential component of exercise capacity. Exercise capacity was only minimally affected by asymptomatic ischemia and was relatively independent of ventricular function.

A Randomized Trial of the Effects of Exercise Training After Coronary Artery Bypass Surgery

Fifty-three male volunteers who had undergone coronary artery bypass surgery were randomized to a medically supervised exercise program (N = 28) or to usual community care (N = 25). They were tested initially and at one year with exercise tests for thallium scintigraphy, maximal oxygen uptake, and electrocardiography. Approximately one third of the patients had signs and/or symptoms of ischemia consistent with incomplete or unsuccessful revascularization. Over the year there were five dropouts, but no major complications occurred. The exercisers attended an average of 82% of the sessions (three times a week) and trained at 80% of their maximal heart rate. Both the exercisers with and those without angina had significant increases in estimated and measured oxygen uptake and significant declines in submaximal and resting heart rate. There was a trend toward improved thallium scans in the exercised patients with angina.

A randomized trial of the effects of 1 year of exercise training on computer-measured ST segment displacement in patients with coronary artery disease

As part of a randomized trial of the effects of 1 year of exercise training on patients with stable coronary artery disease, 48 patients who exercised and 59 control patients had computerized exercise electrocardiography performed initially and 1 year later. The patients who had exercise training as an intervention had a 9% increase in measured maximal oxygen consumption and significant decreases in heart rate at rest and during submaximal exercise. ST segment displacement was analyzed 60 ms after the end of the QRS complex in the three-dimensional X,Y and Z leads and utilizing the spatial amplitude derived from them. Statistical analysis by t testing yielded no significant differences between the groups except for less ST segment displacement at a matched work load, but this could be explained by a lowered heart rate. Analysis of variance yielded some minor differences within clinical subgroups, particularly in the spatial analysis. Obvious changes in exercise-induced ST segment depression could not be demonstrated in this heterogeneous group of selected volunteers with coronary artery disease secondary to an exercise program.

Noninvasive assessment of changes in myocardial perfusion and ventricular performance following exercise training.

Seventeen coronary patients (CAD) underwent thallium (TI-201) treadmill and radionuclide (RNV) ejection fraction supine bicycle testing before and after 5.6 +/- 1.6 (mean +/- SD) months of an exercise program. Thallium data were assessed both using analog images and a computerized circumferential profile technique. Patients exercised on the treadmill to a higher workload after the exercise program, but achieved a similar pressure-rate product. When interpreting the analog thallium images, only 50% agreement was obtained for the assessment of changes in myocardial perfusion (pre/post-training). The computer technique, however, had low inter-intraobserver variability (6%) and better agreement (90.5%). Using the circumferential profile method, five patients improved (a total of 11 regions) and one patient worsened (with two regions). Before the exercise program, the ejection fraction (EF) response to supine bike exercise was normal (an increase greater than 11%) in four, flat in seven, and severely abnormal (a decrease of more than 4%) in six patients. After the exercise program, even though achieving similar or higher pressure-rate products, six patients improved their EF response, nine did not change, and two worsened. Of the five patients who improved their thallium images, one improved his EF response, two remained normal, and two did not change. One patient worsened both his thallium study and the EF response after the exercise program. Changes in thallium exercise images and the EF response to supine exercise occurred in our patients after an exercise program, but were not always concordant. Indeed, of five patients with exercise-induced ischemic ST changes before and after training, the EF response improved in three whereas myocardial perfusion was unchanged. Reasons for this lack of agreement are discussed, and have been considered in the planning of a randomized trial of the effects of an exercise program on myocardial perfusion and function.

Can patients with coronary artery disease receiving beta blockers obtain a training effect

Fifty-nine male volunteers with stable coronary artery disease underwent 1 year of supervised exercise and were compared with 69 similar control patients. Both groups underwent exercise tests initially and at 1 year to determine maximal oxygen uptake. Initial and 1-year tests were performed with patients off all cardiac medications including beta blockers. Although patients had been randomized to exercise intervention, administration of beta blockers was at the prerogative of their physicians. Thirty-seven percent of the trained group and 39% of the control group were taking beta blockers during the year of study. Regardless of whether or not beta blockers were administered, patients in the exercise intervention group had a significant increase in aerobic capacity and improvement in the other hemodynamic markers of training compared with control subjects. Of the trained patients, those on beta blockers were able to comply with the exercise regimen as well as those not taking beta blockers.