Comparison of S-T segment changes on exercise testing with angiographic findings in patients with prior myocardial infarction

Ninety-seven patients with a prior transmural myocardial infarction who underwent coronary angiography and treadmill stress testing were studied retrospectively to assess the reliability of the exercise electrocardiogram in detecting additional disease in patients with a prior infarction. In patients with a previous inferior wall infarction, the S-T response to the treadmill stress test had a high degree of sensitivity (87 percent) and specificity (90 percent) in detecting additional significant coronary artery disease. However, in patients with a previous anteroseptal wall Infarction, the S-T response had much less sensitivity (52 percent), but the degree of specificity remained high (90 percent). In this group a positive test suggested the presence of ischemia in the lateral or inferoposterior region of the myocardium, or both. A negative S-T response was of little value In distingulshing among groups of patients with single or multiple vessel coronary artery disease. The presence of an anterior ventricular aneurysm is most likely responsible for this low sensitivity rate because it generates an opposing force to the ischemic vector, thereby cancelling the S-T segment changes and producing a false negative treadmill stress test. The resting surface electrocardiogram proved useful in predicting a false negative exercise test. The presence of Q waves in the precordial leads extending to lead V₄ or beyond decreased the sensltivity rate of treadmill stress testing to 33 percent.     

Septal Q wave in exercise testing: Angiographic correlation

A study of septal Q wave response in lead CM₅ was carried out to evaluate its usefulness in predicting coronary artery disease. Q wave amplitude was measured in 50 patients with coronary artery disease and 50 normal subjects before and immediately after exercise. In the 100 patients evaluated with coronary angiography, the septal Q wave in lead CM₅ was smaller in patients with coronary artery disease than in normal subjects at rest (probability [p]<0.001) and immediately after exercise (p<0.001). An embryonic (0.5 mm) or absent Q wave in lead CM₅ was significantly more frequent in patients with coronary artery disease than in normal subjects both at rest (76 versus 48 percent) and after exercise (82 versus 16 percent).The sensitivity for S-T depression was 52 percent, the specificity 74 percent and the predictive value 70 percent. The respective values for the Q wave were 82,88 and 87 percent. These differences were not significant (p <0.05). When either a positive S-T or Q wave response was used, the sensitivity increased to 92 percent (p <0.05), and the specificity and predictive values remained unchanged (p <0.01). An Increase in Q wave amplitude with exercise identified a false positive S-T segment response to stress in 75 percent of cases. Absence of the Q wave in lead CM₅ with S-T depression after exercise identified a true positive response in 100 percent of cases.These findings suggest that low Q wave voltage and its failure to increase after exercise imply abnormal septal activation, reflecting loss of contraction associated with ischemia. This finding may be a useful marker for ischemia; the increase in the septal Q wave with exercise may be of value in identifying a false positive S-T segment response.     

Comparison of the multivariate analysis and CADENZA systems for determination of the probability of coronary artery disease

The accuracy of 2 discriminate systems for diagnosis of coronary artery disease (CAD), multivariate analysis (MVA) and Bayesian analysis (CADENZA), was evaluated in 113 patients undergoing electrocardiographic stress testing and coronary angiography. MVA uses weighting factors (F values) generated from our patient data, whereas CADENZA uses probabilities gleaned from an extensive review of the American literature. Overall accuracy was similar. MVA had a higher sensitivity for 1-vessel CAD (75 versus 33%), but CADENZA was better for determining the severity of CAD. The 2 systems provided posterior probabilities for disease that were highly correlated (r = 0.56; p less than 0.001). Both systems suggest the need for further testing based on the probability generated; herein lies their major strength. The application of such systems should help the clinician reach a diagnosis or make a decision as to management in a cost-effective manner.     

Significance of changes in R wave amplitude during treadmill stress testing: angiographic correlation

Coronary angiograms and treadmill stress tests were reviewed in 89 patients. Changes in R wave amplitude were measured in the control and immediate postexercise periods. Of 45 patients with normal coronary arteries, 41 (91 percent) had a decrease in R wave amplitude (P less than 0.01); 3 (7 percent) had an increase in amplitude, including 2 with abnormal left ventriculograms. The remaining patient (2 percent) had abnormal wall motion but no change in R wave amplitude. Among the 44 patients with significant coronary artery disease (70 percent or greater luminal narrowing in one or more vessels), R wave amplitude increased after exercise in 26 (59 percent) with more severe coronary artery disease. R wave amplitude decreased in 18 patients (41 percent) with normal or minimally abnormal resting ventriculograms and less severe coronary artery disease (P less than 0.01). Changes in R wave amplitude reflect ventricular function, an increase in R wave amplitude reflecting more severe dysfunction and severe coronary narrowing. A decreased R wave amplitude indicates normal or minimal dysfunction and is strongly associated with normal coronary angiograms.     

Significance of chest pain during treadmill exercise: correlation with coronary events

A follow-up study of 1,402 patients with a positive maximal treadmill stress test was made to evaluate the significance of angina during the test. Life tables were constructed and evaluated for significance of age, sex and work load at onset of angina. Coronary events (myocardial infarction, progression of angina and coronary death) were twice as frequent in subjects with angina and S-T segment depression as in those without angina. The increased incidence in 4 years held for all coronary events and was still doubled at 7 years for progression of angina and coronary death. The incidence of coronary events was more than twice as great when the angina was induced by a light work load (4 metabolic equivalents = METS) as when it was induced by a heavy work load (8 to 9 METS). Men aged 41 to 50 years having angina during exercise testing had a 3-fold greater incidence of coronary events and a 4-fold greater incidence of myocardial infarction compared with their counterparts who had S-T segment depression alone. In this study, angina during exercise testing identified 85% of true positive tests for coronary artery disease, whereas S-T depression alone identified only 64% of such tests. Thus, angina during exercise testing increases the sensitivity of the test and identifies cohorts of subjects at high risk for subsequent coronary events.     

Predictive accuracy of Q-X/Q-T ratio, Q-Tc interval, S-T depression and R wave amplitude during stress testing.

The sensitivity, specificity and predictive value for $\text{Q-X}\text{Q-T}$ ratio, Q-Tc interval, S-T segment depression, R wave change and various combinations of these criteria were compared in 50 healthy, normal persons and 50 persons with angiographic coronary artery disease defined as 70 percent or greater stenosis of one or more major coronary vessels. Use of a positive S-T segment response and an increase or no change in R wave amplitude as criteria for coronary artery disease resulted in 84 percent sensitivity and 96 percent specificity levels and a 95 percent predictive value. The $\text{Q-X}\text{Q-T}$ and Q-Tc criteria offered no improvement in sensitivity, specificity or predictive value over S-T segment depression.When the study group was limited to 74 persons, 36 without and 38 with angiographically significant coronary artery disease, a Q-Tc interval of 1.08 or more in combination with either slowly or rapidly upsloping S-T depression after exercise predicted coronary disease at a sensitivity level of 76 percent compared with 50 percent with use of the S-T segment alone (P < 0.05). Specificity was not significantly reduced (89 percent for the S-T segment alone, 79 percent with the addition of the Q-Tc interval) (P > 0.05).Use of the R wave response with the presence of upsloping S-T segment depression of 1.5 mm or more 80 msec from the J point improved the sensitivity level from 50 percent for S-T depression alone to 76 percent (P < 0.05); specificity and predictive value were not significantly reduced (81 percent for each [P > 0.05]). The $\text{Q-X}\text{Q-T}$ ratio could be measured in only 55 patients (74 percent) and offered no improvement over S-T segment depression.Upsloping S-T segment depression of 1.5 mm or more 80 msec from the J point in the immediate postexercise period is most likely a positive test for ischemia. An increase or no change in R wave amplitude in response to exercise in these patients regardless of the degree of S-T segment depression is probably indicative of coronary artery disease. In patients with upsloping S-T segment depression, a Q-Tc interval of 1.08 or more in the immediate postexercise period is a useful measurement in predicting coronary artery disease.     

Transient central diabetes insipidus after aortocoronary bypass operations

Three cases of transient central diabetes insipidus after cardiopulmonary bypass are presented. All 3 patients responded promptly to administration of vasopressin, and were completely recovered from polyuria 10 days after cardiac surgery. It is postulated that transient diabetes insipidus after cardiac operation occurred in some patients who had preexisting selective osmoreceptor dysfunction when cardiac standstill during extracorporeal circulation alters the left atrial nonosmotic receptor function, resulting in suppression of antidiuretic hormone release.     

Upsloping S-T segments in exercise stress testing. Six year follow-up study of 438 patients and correlation with 248 angiograms.

A 6 year follow-up study of 438 patients who underwent maximal treadmill stress testing revealed the following annual incidence rate of coronary events (death, myocardial infarction or onset or progression of angina pectoris): 13 percent in 84 subjects whose stress test produced 2 mm downsloping S-T segment depression, 9 percent in 230 subjects with 2 mm horizontal S-T depression and 9 percent in 124 subjects who had an upsloping S-T segment with 2 mm S-T depression measured 0.08 second from the J point. Coronary angiograms were obtained in another group of 248 subjects who underwent maximal treadmill stress testing. They revealed major (greater than 50 percent) obstruction of two or three vessels in 67 percent of 62 subjects with a downsloping S-T pattern on the stress test, in 60 percent of 116 subjects with horizontal S-T depression and in 57 percent of 70 subjects with upsloping S-T depression. Patients with an upsloping pattern of S-T depression during stress testing had the same incidence of coronary events as those with a horizontal pattern of S-T depression. Upsloping S-T depression should not be confused with isolated J point depression. Subjects with an upsloping segment also had the same incidence of major two or three vessel disease as those with horizontal depression. Subjects with a downsloping pattern has a slightly greater incidence of coronary events and major two or three vessel disease.     

Predicting coronary artery disease with treadmill stress testing: changes in R-wave amplitude compared with ST segment depression.

Coronary angiograms and treadmill stress tests were reviewed independently in 108 nonconsecutively selected cases. There were 16 patients (15%) with infarcts on ECG. Changes in R-wave amplitude and ST segments during exercise were evaluated to determine the sensitivity and specificity of each as a predictor of coronary artery disease (CAD). ST segment changes had a sensitivity of 49%, and a specificity of 74%. The sensitivity increased to 55% when infarcts were excluded. R-wave amplitude changes had a sensitivity of 68% and a specificity of 84%. The sensitivity increased to 78% when infarcts were excluded. An index formed by the sum of the change in R-wave amplitude and the magnitude of ST segment change yielded a sensitivity of 76% and specificity of 78%. The sensitivity increased to 84% when infarcts were excluded. There was no statistical difference between specificities for each criteria. Of those patients with an R-wave amplitude decrease, 69% had no coronary artery atherosclerosis, while 31% had significant lesions. Of those patients with no change or an increase in R-wave amplitude, 83% had coronary artery atherosclerosis, while 17% were normal. Of the 83% with coronary artery atherosclerosis, 81% had two and three vessel disease, while only 19% had single vessel disease. No change or an increase in R-wave amplitude during treadmill stress testing is a more reliable indicator of CAD in our laboratory than ST segment changes.     

Use of heart rate responses to standing and hyperventilation at rest to detect coronary artery disease: Correlation with the S-T response to exercise

The heart rate responses to standing and to hyperventilation, expressed as a percent change over the sitting heart rate value, were measured in 48 patients with angiographic coronary artery disease (≥70 percent luminal narrowing) and 50 young, healthy asymptomatic individuals.When an abnormal response suggesting coronary artery disease was defined as an increase in the standing heart rate of <15% over the sitting value and <20% increase in the heart rate to hyperventilation relative to the sitting value, the sensitivity of such a criterion was 56%, the specificity was 92% and the predictive value was 87%. These values were not significantly different (P>0.05) from those for the S-T response to exercise, which were 77%, 98%, and 97% respectively.When either a positive S-T response to exercise or a positive response for control heart rate changes to standing and hyperventilation were used as criteria for a positive test, the sensitivity significantly increased to 98% (P<0.01), while specificity and predictive value remained significantly unchanged (P>0.05) at 90% for each.The use of the heart rate response to standing and hyperventilation may be a useful test in detecting coronary artery disease in patients unable to undergo stress testing. The use of such heart rate responses in addition to S-T depression with exercise results in a highly sensitive and specific test with great predictive value.     

Naloxone and asymptomatic ischemia: failure to induce angina during exercise testing

Endorphins and endorphin receptors are believed to modulate pain perception. To investigate whether naloxone, a specific antagonist, could initiate anginal pain during exercise-induced myocardial ischemia in asymptomatic patients with angiographically defined coronary artery disease, a single-blind trial was conducted in 10 men with prior positive exercise electrocardiograms. Multistage treadmill exercise tests were performed twice within a week. On the second test, patients received naloxone, 2 mg intravenously, by a syringe infusion pump. Exercise was terminated because of fatigue in 6 patients and completion of the protocol in 4. No patient reported chest pain during exercise. Naloxone did not significantly alter exercise duration, heart rate, blood pressure and ST-segment changes compared with control testing. It is concluded that endorphins do not play a significant role in the recognition of anginal pain in patients who have asymptomatic exercise-induced ischemia.     

Nitrofurantoin: Another cause of drug-induced chronic active hepatitis?: A report of a patient with HLA-B8 antigen

Nitrofurantoin, an agent used extensively in chronic urinary tract infections, is rarely incriminated as a hepatotoxin. In this 27 year old women chronic active hepatitis first developed during exposures to nitrofurantoin, and she later suffered exacerbations. Earlier reported cases are reviewed which describe a spectrum of hepatotoxic reactions. This patient has HLA-B8, an antigen associated with autoimmune forms of chronic active hepatitis. It is postulated that the antigen may be associated with liver injury initiated by drugs such as nitrofurantoin.