Positive Exercise Tolerance Test Research Articles

A Comparison of Quality of Life Scores in Patients With Angina Pectoris After Angioplasty Compared With After Medical Therapy

Background Evaluations of therapy for the treatment of angina have traditionally consisted of a combination of objective measures, such as exercise tolerance, and subjective markers, such as angina attack rate. Recently, the need to assess “how patients feel”—their quality of life (QOL)—has been regarded with increasing importance. Standard instruments are available to assess QOL and its change after therapeutic intervention. Although QOL instruments have been used to assess the efficacy of percutaneous transluminal coronary angioplasty (PTCA), they have not been used previously to compare the impact of PTCA with that of medical therapy in patients with angina pectoris. We report on the changes in self-assessed QOL among patients randomly assigned to treatment by PTCA or medical therapy and relate these measurements to changes in exercise performance and coronary angiograms. Methods and Results Patients with stable angina, a positive exercise tolerance test, and at least 70% stenosis (index lesion) in the proximal two thirds of one major coronary artery were randomly assigned to receive PTCA or medical therapy. Six months after randomization, each patient underwent repeat exercise testing and coronary angiography. Before randomization and at the 6-month visit, patients completed a self-administered QOL questionnaire that measured physical functioning and psychological well-being. We compared the changes in QOL with changes between the baseline and 6-month exercise tests, stratified by terciles (decrease in duration, 0- to 2-minute increase, and >2-minute improvement). We also stratified patients by whether there was more or less than 2 SD change (18.8%) in diameter stenosis of the index lesion (initial minus follow-up angiogram), and we related these to changes in QOL measures. One hundred eighty-two patients with one-vessel disease completed baseline and 6-month questionnaires. At baseline, there were no differences in any QOL measurements between treatment groups. At the 6-month follow-up visit, there was greater improvement in both physical functioning and psychological well-being scores for patients receiving PTCA (+7.36±15.6, PTCA; +1.98±14.7, medical therapy; P <.02). Improvement in QOL variables was noted only in patients demonstrating an increase in exercise performance. Also, patients assigned to either treatment whose angiograms demonstrated more than 18.8% improvement in index lesion percent stenosis experienced a significant increase in their QOL scores. Conclusions This was the first study of the relative changes in QOL measures assessed with the use of previously validated and standardized instruments in patients randomly assigned to treatment with PTCA or medical therapy. Patients assigned to PTCA demonstrated a significantly greater improvement in both physical and psychological measures. This improvement was noted in patients whose exercise performance improved and whose angiograms demonstrated an improvement in lesion severity.

Evaluation of Cardiac Damage in Hypertension

Functional and structural alterations of the coronary microcirculation and left ventricular hypertrophy represent the two key cardiac manifestations of arterial hypertension. In addition, qualitative changes in myocardial tissue composition and structure, such as reactive interstitial fibrosis, are frequently present. The extent of the impairment of coronary flow reserve can be measured using Doppler, argon gas chromatography or thermodilution techniques. Impaired flow reserve can be detected non-invasively using positron emission tomography. The combination of both a normal coronary angiogram and a positive exercise tolerance test (electrocardiogram or thallium) strongly indicates the presence of a hypertension-related disorder of the coronary microcirculation. Left ventricular hypertrophy can easily be quantified using echocardiography (Penn formula). Diastolic function can be assessed by measuring mitral inflow using pulsed-wave Doppler echocardiography (E/A ratio). Non-invasive assessment of myocardial structural alternations may be possible in the future using backscatter echocardiography.

Organ Protection

Patients with arterial hypertension often have angina pectoris and a positive exercise tolerance test, even when their epicardial coronary arteries are of normal anatomic appearance. In these patients, coronary vasodilator capacity is frequently impaired by 30-50%, predominantly owing to microvascular alterations. These include medical thickening, decreased capillary density, perivascular fibrosis, and an impaired endothelium-dependent coronary vasodilation. An antihypertensive treatment that can be considered cardioreparative restores myocardial structure through both regression of myocardial fibrosis and regression of the structural coronary microvascular alterations. We believe that this is the first clinical study to show that coronary flow reserve was considerably improved after long-term medical blood pressure normalization.

Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease.

To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning.

Free Radical Markers in Patients with Angina Pectoris and Normal Coronary Angiograms

Markers suggestive of enhanced free radical (FR) activity have been demonstrated in patients with chest pain and normal coronary angiograms. This may be of pathogenetic importance because FRs impair vascular relaxation and are generated following episodes of myocardial ischaemia/reperfusion. Fifteen patients with angina pectoris, normal coronary angiograms and either a positive exercise tolerance test and/or abnormal dipyridamole thallium tomogram were studied along with 15 age-, sex- and smoking-matched controls. A peripheral venous blood sample was obtained to measure the following FR markers: malondialdehyde, plasma thiols, red blood cell glutathione and superoxide dismutase. No significant differences were detected in the levels of any of the FR markers between either the group of 15 patients with chest pain and normal angiograms or the subgroup with positive exercise tolerance tests when compared to the controls. There is therefore no evidence of enhanced FR activity in patients with chest pain and normal coronary angiograms in peripheral venous blood samples.

ACE-inhibitors and coronary microcirculation.

Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris-symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine to what extent under clinical conditions coronary flow reserve can be improved, in hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (Dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with the ACE-inhibitor enalapril (10-20 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, the coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a decrease in LV muscle mass by about 8%, coronary reserve was improved after enalapril by 48%. It is likely that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities at the level of the coronary microcirculation. Consequently, it seems that reparation of hypertensive remodeling of the coronary microcirculation can be induced by ACE-inhibitor therapy.

THE ROLE OF EARLY SURGERY FOLLOWING MYOCARDIAL INFARCTION

SUMMARYThis co‐operative study was a prospective randomised study to evaluate the role of coronary bypass surgery following acute myocardial infarction. The criterion for entry was an early positive exercise tolerance test. All patients who satisfied the clinical criteria of acute myocardial infarction but who were excluded had information on survival obtained after two years. A total of 4658 patients were assessed, with 3334 (71 %) having a modified exercise test. This test was positive in 728 patients, of whom 598 then underwent coronary angiography. Three hundred and forty‐eight patients were randomised (surgery 168, continuing medical treatment 180).At two years the survival in the medical group was 96% and in the surgical group was 93%. At five years the corresponding figures were 88% and 91%. Sub group analyses in terms of age, ejection fraction and extent of vessel disease failed to show any significant differences between those randomised to medicine or surgery. A positive exercise test early after infarction does help to delineate those more likely to require intervention, but a negative exercise test is not an indication for complacency.

Effect of Smoking on the Activity of Ischemic Heart Disease

Cigarette smoking has been causally linked to coronary heart disease. To investigate the effect of smoking on the activity of ischemic heart disease, 65 patients with chronic stable manifestations of coronary disease and a positive exercise tolerance test underwent continuous ambulatory monitoring to quantify the amount of ischemic ST segment depression during daily life. Twenty-four smokers were compared with 41 nonsmokers for frequency and duration of electrocardiographic signs of ischemia during 24 hours. A total of 4,968 hours of ambulatory monitoring were analyzed. The frequency of episodes was three times as often (median) and the duration of ischemia was 12 times longer (median duration, 24 vs 2 min/24 h) in smokers than nonsmokers. This finding remained statistically significant when a number of potentially confounding factors were controlled by means of logistic regression. This study shows that patients with coronary artery disease who smoke have significantly and substantially more active myocardial ischemia during daily life than patients who do not.

Effect of smoking on the activity of ischemic heart disease

Cigarette smoking has been causally linked to coronary heart disease. To investigate the effect of smoking on the activity of ischemic heart disease, 65 patients with chronic stable manifestations of coronary disease and a positive exercise tolerance test underwent continuous ambulatory monitoring to quantify the amount of ischemic ST segment depression during daily life. Twenty-four smokers were compared with 41 nonsmokers for frequency and duration of electrocardiographic signs of ischemia during 24 hours. A total of 4,968 hours of ambulatory monitoring were analyzed. The frequency of episodes was three times as often (median) and the duration of ischemia was 12 times longer (median duration, 24 vs 2 min/24 h) in smokers than nonsmokers. This finding remained statistically significant when a number of potentially confounding factors were controlled by means of logistic regression. This study shows that patients with coronary artery disease who smoke have significantly and substantially more active myocardial ischemia during daily life than patients who do not.

Frequency of painless myocardial ischemia during exercise tolerance testing in patients with and without diabetes mellitus

To evaluate the frequency of painless myocardial ischemia, all patients with positive exercise tolerance test responses (at least 2 mm of ST depression) from 1983 to 1985 were examined. Of the 211 patients with exercise-induced ischemia, 101 (48%) did not have pain during the ischemic period; 26 (12%) had diabetes mellitus, 24 of whom (92%) had type II diabetes mellitus. Lack of pain was not correlated with age, gender, history of cigarette smoking, systemic hypertension, past acute myocardial infarction, coronary artery bypass grafting, use of beta-blocking or calcium-channel blocking drugs, number of narrowed coronary arteries or average calculated ejection fraction at cardiac catheterization. Patients with painless myocardial ischemia were less often taking nitrates (39% vs 55%, p less than 0.05) and reported prior episodes of chest pain less often (50% vs 82%, p less than 0.01) than control subjects. There was no difference in the frequency of painless myocardial ischemia between patients with and without diabetes mellitus (54% vs 47%). Duration of exercise was shorter in patients with diabetes mellitus and in patients who had pain with myocardial ischemia. No significant difference in age, gender, use of nitrates, beta-blocking or calcium-channel blocking drugs, history of myocardial infarction, angina pectoris or cigarette smoking was found between diabetic and nondiabetic patients. Systemic hypertension was more common in diabetic patients. Thus, painless myocardial ischemia is common in our patients with positive exercise tolerance test responses, but its frequency is similar in diabetic and nondiabetic patients.

Evaluation and Treatment of the Asymptomatic Patient with a Positive Exercise Tolerance Test

A positive exercise study in an asymptomatic patient presents a clinical dilemma. Many of these asymptomatic positive studies are false-positive, but a subset of these patients have silent coronary artery disease. Other noninvasive tests can be used in conjunction with exercise testing to help identify this subset of patients, but coronary angiography is often ultimately necessary to ensure an accurate diagnosis. An algorithm for the evaluation and treatment of the patient with an asymptomatic positive exercise study is proposed.

Serial studies of platelet factor 4 and beta thromboglobulin during exercise in patients with coronary artery disease

In vivo activation of platelets can be accurately measured by radioimmunoassays of platelet factor 4 (PF4) and beta thromboglobulin (βTG). Studies that attempt to correlate increases in PF4 and βTG levels with exercise-induced myocardial ischemia have yielded conflicting results. To further examine the natural history of release of PF4 and βTG we used a method of serial samplings of these proteins during and after exercise in nine normal subjects and 24 patients with coronary artery disease (CAD). Mean values for PF4 and βTG at rest, during each stage, and immediately after treadmill exercise were the same for normal subjects and for patients with positive and negative responses to exercise-tolerance tests (ETTs). However, nonparametric analysis and regression equations disclosed differences in trends of PF4 level during exercise; PF4 levels increased in normal subjects during exercise, while patients with positive ETTs had no change in PF4 levels and patients with negative ETTs actually showed a decrease in PF4. This investigation confirmed that exercise-induced myocardial ischemia is not associated with platelet aggregation as manifested by the release of the platelet-specific proteins PF4 and βTG. Statistical analysis suggested that prior reports of elevated levels of PF4 during exercise could have been caused by technical and methodologic difficulties that were associated with the collection and handling of the samples.

Propranolol-verapamil versus propranolol-nifedipine in severe angina pectoris of effort: A randomized, double-blind, crossover study

To compare a propranolol-verapamil with a propranolol-nifedipine combination in patients with severe angina of effort, 16 patients (11 men and 5 women, aged 56 ± 8 years [mean ± standard deviation]) with more than 5 episodes/week of angina and a positive exercise tolerance test despite propranolol (229 ± 44 mg/day [range 180 to 360]) were maintained on this dose of propranolol and, in addition, received verapamil (360 mg/day) and nifedipine (60 mg/day) for 3 weeks each in a double-blind, randomized fashion. In comparison with propranolol alone, anginal frequency and nitroglycerin usage were reduced by propranolol-verapamil but not by propranolol-nifedipine. Exercise time (standard Bruce protocol) was similar for the 2 combinations (6.4 ± 2.0 minutes with propranol-olverapamil, 6.6 ± 2.1 minutes with propranolol-nifedipine, difference not significant), but the magnitude of ST-segment depression at peak exercise was less (p < 0.05) during propranolol-verapamil (0.03 ± 0.06 mV) than during propranolol alone (0.18 ± 0.07 mV) and propranolol-nifedipine (0.08 ± 0.07 mV). Left ventricular ejection fraction at rest was higher (p < 0.05) with propranolol-nifedipine (0.62 ± 0.10) than with propranolol-verapamil (0.58 ± 0.10), but neither differed from ejection fraction at rest with propranolol alone (0.59 ± 0.08). Ejection fraction at peak exercise was similar during all 3 periods. In 2 patients, verapamil caused weakness, lightheadedness, and severe sinus bradycardia (40 to 48 beats/min), and the dosage was reduced (blindly) to 240 mg/day, with the alleviation of bradycardia and associated symptoms. Thus, in patients with severe angina of effort with propranolol alone, the addition of verapamil is more effective than the addition of nifedipine in reducing anginal frequency, nitroglycerin usage, and the magnitude of the electrocardiographic response to exercise. Although both combinations are generally safe and well-tolerated, in an occasional patient symptomatic sinus bradycardia develops during therapy with propranolol-verapamil; therefore, this combination must be given carefully.

A multivariate approach for interpreting treadmill exercise tests in coronary artery disease.

To determine the value of a multivariate approach for the analysis of the treadmill exercise tolerance test (ETT), 237 patients referred for evaluation of chest pain who underwent a standard Bruce protocol ETT and coronary arteriography were studied. Predictive value of a positive ETT was 0.78 (43/55) using 1.0--1.9 mm ST segment depression criterion, 0.97 (59/61) using greater than or equal to 2.0 mm ST segment depression. When the 1.0--1.9 mm ST criterion was combined with peak systolic blood pressure-heart rate product (double product) less than or smaller than 23,000, exercise duration less than 6 minutes, and ST depression for greater than 3 minutes into recovery, predictive value improved to 0.89 in 18 patients with any two of the above. Predictive value for multivessel disease was also improved using non-ST criteria. Predictive value of a negative ETT for absence of coronary artery disease was 0.60 (29/48), and was 0.86 (12/14) if double product was greater than or equal to 30,000. Presence of chest pain during ETT did not improve predictive value of any type of test. Digitalis ingestion in 33 patients was not associated with decreased predictive value of a positive test. These data suggest that the predictive value of both positive and negative ETT in a symptomatic population can be improved with a multivariate approach.

Clinical correlates of coronary cineangiography in young males with myocardial infarction

Thirty-eight men who suffered acute transmural myocardial infarction before age 40, and after recovery were New York Heart Association functional Class I or II, were studied by noninvasive means and by coronary angiography in order to determine whether these nonivasive studies could predict the presence of significant coronary artery disease remote from that felt to be responsible for the previous myocardial infarction. Patients were divided into two groups on the basis of the absence (Group I) or presence (Group II) of obstructive disease in a major coronary artery supplying myocardium remote from the prior myocardial infarction. There were 21 patients in Group I and 17 patients in Group II. They did not differ with respect to age, abnormalities of lipid or glucose metabolism, family history, history of hypertension or cigarette use, presence of obesity, or infarct localization. Ten of 17 patients in Group II had angina pectoris; only 3/21 patients in Group I had angina pectoris (p less than 0.01). All 12 patients tested in Group II had a positive maximal exercise tolerance test; only 1/17 patients tested in Group I was similarly positive (p less than 0.001). The absence of angina pectoris and the presence of a negative maximal exercise tolerance test is strong evidence against the pressure of significant CAD remote from that responsible for the prior myocardial infarction.

Cardiac syndrome X – a challenge for Cardiologist

Cardiac syndrome X is a multifactorial disorder. A triad of angina pectoris, positive exercise tolerance test (ETT) and angiographically normal epicardial coronary arteries, is called Cardiac syndrome X. Though the normal epicardial coronary arteries, patients present with debilitating chest pain which increases morbidity and poor quality of life. The particular cause of Cardiac syndrome X is still unknown. Many large trails are on going to detect exact pathogenesis of this condition. A multiple treatment regimens may reduce the morbidity and improve the quality of life of these patients. Key words: Angina pectoris; exercise tolerance test. DOI: 10.3329/uhj.v6i1.7188University Heart Journal Vol.6(1) 2010 pp.32-34

Effects of erythrol tetranitrate and amotriphene on exercise tolerance tests in angina pectoris.

Sublingual erythrol tetranitrate is a potent drug in counteracting coronary insufficiency, as evidenced by reversal of positive electrocardiographic exercise tolerance tests in 72 per cent of 36 cases and reduction of anginal attacks in them by more than 50 per cent. Comparative studies with amotriphene indicate some subjective alleviation of angina, but objective reversals of the electrocardiographic effects of exercise in only 16 per cent of the cases. Side effects of erythrol tetranitrate, particularly headache, are seen in a minority of cases and are often circumvented by starting with a small dose and gradually increasing it as necessary. Alleviation of ectopic beats on exercise occurred equally in a minority of cases on the two drugs.

Multiple variations of WPW conduction in one subject: Intermittent normal conduction and a false positive exercise tolerance test

A case is presented demonstrating a number of important facets of the WPW syndrome: (1) Multiple variation in ventricular excitation; (2) intermittent normal electrocardiograms; (3) variations in the P-R interval with P-R intervals of 0.14 second in the presence of pre-excitation; (4) ST segment and T wave changes secondary to pre-excitation (this leads to a false impression of a positive exercise tolerance test); (5) conversion to normal conduction. No other arrhythmia or indication of underlying cardiac disease was noted.

The electrocardiographic syndrome of short P-R interval and broad QRS complexes: A clinical study of 80 cases

1. 1. An analysis is made of 80 patients with the syndrome of short P-R interval and broad QRS complexes, seen at the University of Texas Medical Branch. 2. 2. Incidence of the syndrome is infrequent, being 1.5 per 1,000 patients. 3. 3. Ages varied from 9 1 2 months to 82 years, and 35 were over 40 years old. There was a slight predominance of males (60 per cent). Incidence in the Negro was infrequent. 4. 4. Forty-eight patients (60 per cent) had no evidence of organic heart disease. Nineteen had coronary heart disease. Seven showed clinical evidences of acute myocardial infarction, but the ECG diagnosis was generally obscured by the broad QRS complexes. 5. 5. There was a high incidence of psychiatric diagnoses (26 per cent). Seven patients subjected to electroshock and deep insulin shock therapies tolerated them well. 6. 6. Successive tracings characteristically showed considerable variation. Even in otherwise diagnostic tracings, the P-R interval may occasionally exceed 0.12 second, but the concertina effect can be demonstrated. 7. 7. There were 48 patients showing a QRS configuration of the Group B of Sodi-Pallares, and 13 patients of Group A. Sixteen had indeterminate patter 8. 8. Effects of exercise, carotid sinus pressure, and various drugs on the ECG manifestations were confirmed. False positive Master exercise tolerance tests were demonstrated. 9. 9. Forty-five patients (56 per cent) had arrhythmias, and we observed 29 with atrial tachycardia, 6 with atrial fibrillation, and 2 with atrial flutter. In 14 patients, the arrhythmias complicated organic heart disease. 10. 10. Broad QRS complexes during the arrhythmias were more frequent than previously reported, and simulated ventricular tachycardia and ventricular fibrillation. 11. 11. Two older patients died suddenly, presumably as a result of a mechanism disorder. 12. 12. The usual methods of control of atrial tachycardia were found efficacious. Pronestyl intravenously under ECG control appeared to be the most effective method of reversion of atrial fibrillation.