Role of exercise testing in predicting sudden death.

The exercise test can be utilized to identify a subset of patients with coronary heart disease who are at increased risk of subsequent cardiac mortality including sudden cardiac death. The exercise test variables that best identify these high risk patients differ according to clinical subsets, but exercise duration, ST segment depression and ventricular arrhythmias on the electrocardiogram are the most important variables. In the clinical setting, the exercise test is of limited value for identifying the patient at risk for developing sudden cardiac death because its sensitivity and specificity are not high enough. However, the exercise test does provide prognostic information that is independent of other clinical variables and it may prove to be of clinical utility when combined with multiple other prognostic variables.

Ambulatory electrocardiographic monitoring: can we predict sudden death?

Cardiac arrhythmias can be accurately detected and quantified using ambulatory electrocardiographic monitoring. From a review of major studies, it appears that the presence of advanced ventricular arrhythmias identifies a subset of patients with coronary heart disease who are at a relatively higher risk for sudden death than are those patients without such arrhythmias. Left ventricular dysfunction is an independent and additive risk factor for subsequent development of sudden cardiac death. The presence of high grade ventricular arrhythmias appears to increase the risk for sudden death in patients with hypertrophic and dilated cardiomyopathy. Ambulatory monitoring can be used to identify a subset of patients with coronary disease or cardiomyopathy who are at increased risk for sudden cardiac death. Because of the relatively low overall incidence of sudden cardiac death in such patients, and the low sensitivity and specificity for accurately classifying patients, the practical applicability of this technique to large population subgroups is limited.

Behavior of the terminal T wave during exercise in normal subjects, patients with symptomatic coronary artery disease and apparently healthy subjects with abnormal ST segment depression.

The Q-T interval and apex of T wave to end of T wave (aT-eT) interval were measured by computer in four age-matched study groups at rest and during exercise to determine whether: the behavior of the aT-eT interval differs in patients with myocardial ischemia when compared with normal subjects, and the behavior of the aT-eT interval differs in subjects with true positive and false positive ST segment responses. Group I consisted of 57 normal subjects. Group II consisted of 41 symptomatic patients with documented coronary artery disease. A group of apparently healthy subjects with asymptomatic ST segment depression during exercise was divided into two additional groups: Group III, those without coronary artery disease; and Group IV, those with coronary artery disease. Subjects were excluded from the study if they had left ventricular hypertrophy or an intraventricular conduction defect or were taking digitalis or type I antiarrhythmic agents. There were no significant differences in the aT-eT interval and aT-eT/Q-T ratio among the four study groups when compared at rest; however, during exercise at similar heart rates, the aT-eT interval was significantly shorter and the aT-eT/Q-T ratio significantly smaller in Groups II and IV, the subjects with coronary artery disease, than in Group I, the normal subjects. The aT-eT interval and aT-eT/Q-T ratio measurements in Group III did not differ from those in Group I at rest or during exercise. In conclusion, the aT-eT interval and aT-eT/Q-T ratio may reflect changes in myocardial repolarization in exercise-induced ischemia and may have potential for future clinical application.

Exercise echocardiographic detection of coronary artery disease in women.

The utility of exercise echocardiography for the diagnosis of coronary artery disease has been demonstrated in populations consisting largely of men with a high prevalence of disease. To determine the diagnostic value of exercise echocardiography in women, 57 women who presented with chest pain were studied with coronary cineangiography and echocardiography combined with either treadmill (n = 38) or bicycle exercise (n = 19). Significant coronary artery disease (greater than or equal to 50% reduction in luminal diameter) was present in 28 (49%) of 57 patients, including 16 (84%) of 19 who had typical angina, and 12 (32%) of 38 who had atypical chest pain. The overall sensitivity and specificity of echocardiography were both 86%. Exercise echocardiography correctly determined the presence or absence of coronary artery disease in 32 (84%) of 38 patients who had atypical chest pain and in 17 (89%) of 19 who had typical angina (p = NS). The exercise electrocardiogram (ECG) was nondiagnostic in 17 patients (30%) who had rest ST segment depression or ST depression with exercise that could also be induced by hyperventilation or changes in position. The correct diagnosis was made by echocardiography in 14 (82%) of 17 patients with a nondiagnostic exercise ECG. In conclusion, exercise echocardiography has a clinically useful level of sensitivity and specificity for the detection of coronary artery disease in women. The technique provides diagnostic information in women presenting with atypical chest pain and in those who have a nondiagnostic exercise ECG.

Normalization of abnormal T waves in ischemia.

Inverted T waves due to coronary artery disease and previous myocardial infarction were observed to revert ot normal, upright position during ischemia in 38 patients. The normalization of inverted T waves was seen on the electroencephalograms of 19 patients during spontaneously occurring angina pectoris and of 11 patients when ischemia was provoked by treadmill exercise; for 8 patients, normalization occurred during the administration of isoproterenol hydrochloride and during the consequent episode of angina pectoris. The mechanism for normalization may be the algebraic sum of the extent of ST segment elevation and the amplitude of the T waves of acute ischemia plus the extent of preexisting ST segment depression and the degree of T wave inversion, to result in isoelectric ST segment and upright T wave. As with myocardial infarction, reciprocal changes may also be recorded. However, the reciprocal nature may be masked since either acute ST segment elevation of T wave inversion, or both, may not be recorded in the leads reflecting the ischemic area because of normalization.

Resting U wave inversion as a marker of stenosis of the left anterior descending coronary artery.

Resting 12-lead electrocardiographic records from 849 patients who underwent coronary cineangiographic studies were reviewed for U wave negativity without knowledge of the clinical data or angiographic results. In order to evaluate U wave negativity as an independent electrocardiographic sign, patients with significant Q waves in the anterior leads were excluded from the final data analysis leaving 760 patients. Twenty-seven patients had U wave negativity in leads I, aVL or V4 through V6. For the study population, the prevalence of coronary artery disease was 64 percent (484 or 760); the prevalence of significant left anterior descending or left main coronary artery stenosis was 46 percent (350 of 760); and the prevalence of angiographic left ventricular dysfunction was 41 percent (309 of 754). Among 27 patients with resting U wave negativity the prevalence of coronary artery disease was 89 percent (24 of 27); the prevalence of left anterior descending or left main disease was 89 percent (24 of 27); and the prevalence of angiographic left ventricular dysfunction was 80 percent (20 of 25). Among patients selected for coronary cineangiographic study, U wave negativity was a significant predictor (p < 0.001) of greater than or equal to 75 percent stenosis of the left anterior descending or left main coronary artery and of left ventricular dysfunction (p < 0.001).

Role of exercise stress testing in healthy subjects and patients with coronary heart disease. Controversies in cardiology--I.

The value of the exercise stress test in the evaluation of clinically healthy subjects and patients with coronary heart disease is not limited to the isolated interpretation of abnormalities of the S-T segment. Other measurable parameters which are of diagnostic and prognostic importance include: (1) a decrease in systolic blood pressure during exercise; (2) the appearance of complex ventricular arrhythmias of low exercise heart rates; (3) the appearance of inverted U waves during or after exercise; (4) the patient's maximal exercise capacity; and (5) new auscultatory findings postexercise. The reliability of the exercise test as a diagnostic tool is futher enhanced by proper patient selection and careful attention to exercise techniques. Subjects with labile ST-T wave changes during standing hyperventilation, fixed ST-T changes at rest, and intraventricular conduction defects are not ideal candidates for "diagnostic" stress testing and the examining physician must rely more heavily on nonelectrocardiographic findings. The criteria used to define an abnormal S-T response will vary according to the lead system used. However, in both symptomatic and asymptomatic subjects the appearance of marked degrees of S-T depression at low exercise heart rates significantly increases the probability of finding advanced coronary disease, particularly if the S-T depression is seen in multiple monitoring leads and is of prolonged duration postexercise.

Relation of exercise-induced physiologic S-T segment depression to R wave amplitude in normal subjects.

Exercise electrocardiography was performed in 100 asymptomatic male volunteers with a mean age of 42.6 years. The R wave and total RS amplitude and the magnitude of physiologic S-T segment depression at the J junction were quantitated for a modified bipolar CC5 lead and a vertically oriented bipolar lead (VL) using computer-averaged groups of 25 consecutive QRS complexes from each of seven stages of rest and exercise. Computer-generated X-Y plots were used to examine the correlations between the magnitude of S-T depression and the R wave and total RS amplitudes. The magnitude of S-T depression and of the R wave amplitude were unrelated at standing rest but showed increasing correlation with progressive increases in exercise heart rate (correlation coefficient = 0.425, p < 0.00001 at maximal exercise). The total RS amplitude was also related to the magnitude of S-T depression during exercise, but the correlations did not improve progressively with increases in exercise heart rate. The magnitude of S-T depression was more closely related to R wave amplitude and total RS amplitude in the vertically oriented lead than in the CC5 lead. These data demonstrate a significant relation between the magnitude of R wave and total RS amplitudes and the magnitude of physiologic S-T segment depression in normal subjects during exercise. They suggest the need for evaluation of S-T depression corrected for R wave amplitude in an attempt to improve the diagnostic accuracy of the exercise electrocardiogram. The data also suggest that the criteria for abnormal S-T depression should take into consideration the different R wave voltages reflected by different types of recording leads.

Comparative study of exercise-induced ventricular arrhythmias in normal subjects and patients with documented coronary artery disease.

The incidence, types and patterns of emergence of treadmill exercise induced ventricular arrhythmias were studied in 482 subjects with and without coronary heart disease. All subjects were free of premature ventricular complexes at rest and were classified into groups on the basis of their clinical status. In Group 1A were 141 patients with chest pain and normal coronary arteriograms and in Group IB 144 age-matched subjects free of clinical evidence of heart disease. Group II consisted of 197 patients with chest pain and arteriographically documented coronary artery disease. Patients in Group IA and II exercised to at least 85% of their predicted maximal heart rate or until chest pain occurred. Subjects in Group IB underwent maximal exercise testing. The total incidence of exercise-induced ventricular arrhythmias was 16% in Group IA, 44% in Group IB and 29% in Group II. However, when exercise heart rate at the time of appearance of ventricular arrhythmias was taken into account the incidence of exercise-induced ventricular arrhythmias up to a heart rate of 130/min was 27% in the patients with documented coronary artery disease (Group II) compared with rates of 9 and 6%, respectively, for Groups IA and IB (P less than 0.001). The incidence rates of multifocal ventricular premature complexes, ventricular tachycardia and ventricular premature complexes at a rate of more than 10/min were also significantly greater at submaximal heart rates in the patients with coronary disease. Patients with three vessel coronary artery disease and abnormal left ventricular wall motion had a significantly greater incidence of exercise-induced ventricular arrhythmias. The incidence of exercise-induced ventricular arrhythmias in patients with coronary disease and a positive S-T segment response was not significantly increased.

Comparative study of cardiovascular function and ventricular premature complexes in smokers and nonsmokers during maximal treadmill exercise.

Maximal treadmill exercise tests were performed by 586 male members of the Indiana State Polic Force who were free of clinical evidence of cardiovascular disease. The study population was categorized into groups according to cigarette smoking experience and subgroups according to age and number of pack-years of exposure. There were 176 nonsmokers (30 percent), 268 current smokers (46 percent) and 142 former smokers who had abstained for at least 1 year (24 percent). No statistically significant differences were found in the prevalence of exercise-induced ventricular premature complexes when current smokers were compared with nonsmokers or former smokers either as a group or as subgroups classified by age. The duration of maximal exercise and the peak heart rate and systolic blood pressure during maximal exercise were compared for each group. The duration of maximal exercise was significantly shorter in smokers (P less than 0.001) and former smokers (P less than 0.005) than in nonsmokers. Maximal systolic blood pressure during exercise was greater in smokers than in nonsmokers (P less than 0.01) but did not differ significantly between nonsmokers and former smokers. Maximal heart rate during exercise was significantly lower in smokers (P less than 0.01) and former smokers (P less than 0.01) than in nonsmokers. In conclusion, there was a statistically significant difference in the duration of exercise and the maximal heart rate and systolic blood pressure attained during exercise between men who smoked and nonsmokers, but the prevalence of the exercise-induced ventricular premature complexes did not appear to be influenced by smoking habits.

Prevalence and reproducibility of exercise-induced ventricular arrhythmias during maximal exercise testing in normal men.

The occurrence of ventricular arrhythmias at rest or during ordinary daily activities has been implicated as a risk factor for future coronary-related events and sudden death. However, the clerical significance of exercise-induced ventricular arrhythmias remains uncertain. To assess the prevalence and reproducibility of such arrhythmias, two serial maximal treadmill exercise tests were performed in a study population of 543 male Indian State policemen at an average interval of 2.9 years. Four hundred sixty-two subjects were clinically free of evidence of cardiovascular disease, and 81 had evidence of definite or suspected cardiovascular disease. The prevalence of exercise-induced ventricular arrhythmias during the first test was 30% in men aged 25 to 34 years, 32% in those aged 35 to 44 years and 36% in those aged 45 to 54 years. The prevalence rate in these age groups with repeat testing was 36, 38 and 42%, respectively. These differences were not statistically significant. The group with definite or suspected cardiovascular disease had a greater prevalence of exercise-induced ventricular arrhythmias than normal subjects during both tests but the prevalence rate with repeat testing remained constant. The occurrence of exercise-induced ventricular arrhythmias was reproducible in individual subjects during the second test in 55% of 25 to 34 year olds, 58% of 35 to 44 year olds and 62% of 45 to 54 year olds. Thus, individual reproducibility in two consecutive tests was only slightly greater than reproducibility by chance alone. The group with known or suspected cardiovascular disease demonstrated a trend toward greater reproducibility with repeat testing. Exercise-induced ventricular arrhythmias were not reproducible by type or complexity. The marked variability of exercise-induced ventricular arrhythmias during repeat maximal exercise testing in a clinically normal population appears to negate the usefulness of this finding during a single test as a marker of future cardiovascular disease. Nevertheless, subjects whose arrhythmias were reproducible may form a group destined to manifest clinical cardiovascular disease in long-term follow-up studies.

Computer quantitation of Q-T and terminal T wave (aT-eT) intervals during exercise: methodology and results in normal men.

Computer-quantitated measurements of the Q-T intervals, the Q-T/Q-Tc ratio (Q-T/corrected Q-T) and the terminal T wave (apex to end of T [aT-eT] interval) were evaluated in resting and exercise electrocardiograms of 130 normal men with a mean age of 40 years. Pseudo-orthogonal, bipolar X, Y and Z axis leads were recorded during treadmill exercise testing, and 25 consecutive QRS-T complexes from standing rest and three exercise stages were computer-averaged. The Q-T intervals, Q-T/Q-Tc ratio and aT-eT interval measurements were then computed in the X and Z axis leads only, because the Y lead proved to be too noisy for accurate interpretation. A correlation coefficient of 0.9830 resulted between measurements made manually from the plotted, composite QRS-T complexes and those made by computer. No significant differences , in the paired sense, were found between any of the measurements. Measurements made on the Z axis lead; however, the differences in the measurements remained constant across all stages of exercise. A Q-T/Q-Tc ratio of greater than 1.08, previously reported to be a reliable indicator of coronary disease, was observed in the majority of our normal subjects during exercise. Although the Q-T interval is substantially influenced by many factors, the aT-eT interval proved not to be age- or heart rate-dependent. It appears that the aT-eT interval can be measured with a high degree of reliability during exercise and it may prove to be a relatively specific indicator of repolarization alterations that occur with myocardial ischemia.

Prevalence and magnitude of S-T segment and T wave abnormalities in normal men during continuous ambulatory electrocardiography.

Fifty asymptomatic normal male volunteers, mean age 44.6 years (range 35 to 59), were prospectively studied to ascertain the prevalence and magnitude of S-T segment and T wave changes detected during continuous ambulatory electrocardiographic monitoring. Transient S-T segment depression of 1.0 mm or more was recorded in 15 (30 percent) of the subjects, and labile T wave inversion of up to 3 mm occurred in an additional 18 (36 percent). The presence of ST-T changes during monitoring did not correlate with age, daily activity status or heart rate. There was also no correlation with the S-T segment response or work performance during treadmill exercise testing. It is concluded that S-T segment depression and T wave inversions are commonly observed during ambulatory electrocardiographic monitoring of normal men. Therefore, similar changes observed in patients with coronary artery disease should be interpreted with caution.

Usefulness of Q-wave response to exercise as a predictor of coronary artery disease.

In lead CM5, the Q-wave response to exercise has been reported as an effective index in predicting coronary artery disease (CAD) and CAD with left anterior descending (LAD) disease. The purpose of this study was to verify these findings when the Q wave was analyzed in lead CC5 in 135 patients. The sensitivity for abnormal ST depression was 77%, specificity 83% and predictive value 78%. The corresponding values for the abnormal Q-wave response (reduction or no change in Q-wave amplitude) were 70%, 61% and 59%. These differences (except sensitivity) were significant. When either a positive ST or Q-wave response was used, sensitivity, specificity and predictive value did not significantly increase compared with the ST segment alone. In addition, only 45% of normal subjects with false-positive ST depression had a normal Q-wave response (increase) and 57% of patients with false-negative ST responses had an abnormal Q-wave response. When a positive response for CAD with an LAD lesion and for multivessel CAD with LAD narrowing was defined as having a Q-wave reduction, the sensitivities were extremely low (15% and 17%), but both the specificities and the predictive values were 100%. Therefore, the Q-wave analysis in lead CC5 is no more sensitive for detecting CAD than the ST-segment response. However, when a decreased Q-wave amplitude is observed, multivessel CAD and LAD narrowing can be predicted.

Masking of exercise-induced ST-segment depression by rate-dependent left-axis deviation.

An unexpected high incidence of false negative ST-segment responses to exercise was previously reported for patients with coronary artery disease and abnormal left-axis deviation on their resting electrocardiograms. In the case presented, an exercise-induced, "ischemia" ST-segment depression was masked with the onset of rate-dependent left-axis deviation. The state of the base-line electrocardiogram is an important but often overlooked factor in assessing the incidence of false negative and false positive ST-segment responses to exercise.