Serial exercise testing in patients with effort angina: variable tolerance, fixed threshold

To investigate the frequency and mechanism of variable threshold angina, seven treadmill exercise tests were performed in each of 28 patients with stable effort angina and exercise-induced ST segment depression. Each patient had tests at 8 AM on 4 days within a 2 week period and on 1 of these days had three additional tests at 9 AM, 11 AM and 4 PM. Time to 1 mm ST depression increased from 277 +/- 172 seconds on day 1 to 319 +/- 186 seconds on day 2, 352 +/- 213 seconds on day 3 and 356 +/- 207 seconds on day 4 (p less than 0.05). Rate-pressure product at 1 mm ST depression remained constant. Similarly, time to 1 mm ST depression increased from 333 +/- 197 seconds at 8 AM to 371 +/- 201 seconds at 9 AM and to 401 +/- 207 seconds at 11 AM and decreased to 371 +/- 189 seconds at 4 PM (p less than 0.01). Again, rate-pressure product at 1 mm ST depression remained constant. The standard deviation for time to 1 mm ST depression, calculated as a percent of the mean for each patient's seven tests and then averaged for the entire group, was 22 +/- 11%. The standard deviation for rate-pressure product at 1 mm ST depression, calculated in the same way, was significantly less at 8.4 +/- 2.8% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased release of nitric oxide in ischemic hearts after exercise in patients with effort angina

Objectives. The aim of this study was to determine whether the release of nitric oxide (NO) from the ischemic heart increases during exercise in patients with effort angina.Background. Myocardial ischemia increases NO production in the canine heart, but no such increase has been demonstrated in the ischemic human heart.Methods. Fifteen patients with effort angina underwent supine ergometer exercise tests. All patients had severe proximal stenosis (>90%) in the left anterior descending coronary artery. The control group consisted of 17 subjects without coronary artery disease or systemic hemodynamic abnormalities.Results. Neither the lactate extraction ratio (LER) nor the difference in NO concentration between coronary venous and arterial blood (ΔVA[NO]) was affected by exercise in the control subjects. In patients with effort angina, neither variable differed from that in the control group at rest; however, exercise markedly decreased LER and significantly increased ΔVA(NO) (from 4.7 ± 0.3 to 16.5 ± 1.6 μmol/liter, p < 0.001) in the patient group. The extent of decrease in LER was significantly correlated with the extent of increase in ΔVA(NO) in the patients with effort angina (r²= −0.837, p < 0.001).Conclusions. Provocation of myocardial ischemia by exercise stress increases NO production in the hearts of patients with effort angina.     

平板运动试验时的心率血压反应与缺血阈值

目的 研究平板运动试验时的心率血压反应与缺血阈值。方法 选择不典型胸痛的病人５７６例,男３６８例,女２０８例,年龄为４０￣６０岁之间,采用Ｍａｒｑｕｅｔｔｅ ＭＡＸ－１活动平板,Ｂｒｕｃｅ修正方案,运动过程中监测心率、血压的变化。结果 所有检者均已达到最大预计心率的８５％以上,但运动试验阳性组所达到的心率、及运动时间（Ｔ）低于其他组,最大ＳＴ段／心率斜率（ｍａｘｉａｌ ＳＴ／ＨＲ ｓｌｏｐｅ）、代     

Elevated pain threshold in patients with effort-induced angina pectoris and asymptomatic myocardial ischemia during exercise test

The purpose of the present study was to analyze the prevalence of asymptomatic (silent) myocardial ischemia during exercise testing among patients with effort-induced angina pectoris, and further, to compare the pain threshold of patients with symptomatic and asymptomatic myocardial ischemia. A group of 26 patients comprised the study. In half of the patients myocardial ischemia during the exercise testing was silent and in one half it was symptomatic. Asymptomatic myocardial ischemia was defined as an asymptomatic ST-segment depression greater than or equal to 0.1 mV, lasting longer than 60 s during an exercise test. In patients with asymptomatic ischemia the pain thresholds both on toe and finger were significantly higher than in patients with symptomatic ischemia: mean values were 10.1 versus 4.9 mA on the toes, p less than 0.025, and 8.4 versus 2.5 mA on the fingers, p less than 0.01. We conclude that asymptomatic myocardial ischemia during exercise test is seen often in patients with angina pectoris and that this may be due to an increased pain threshold.     

Circadian variation of ischemic threshold in patients with chronic stable angina.

Circadian variation of ischemic threshold in chronic stable exertional angina was determined in 51 patients with documented coronary artery disease from the Holter monitor results. The peak favored time zones of ischemic attacks were 8 a.m. and 9 a.m. There was no difference in frequency of ischemic attacks, magnitude of ST-segment depression, or duration of ST-segment depression between the two time zones for ischemic attacks, 6-9 a.m. and 0-3 p.m., but the ischemic threshold was lower in the morning than in the afternoon. These observations suggest that the pathogenesis of ischemic attacks differs from one time zone to the other and is considered helpful in planning therapeutic strategies for myocardial ischemia.     

Effects of myocardial revascularisation in patients with effort angina and those with effort and nocturnal angina

The effects of coronary artery bypass graft operation were studied in 32 patients with daytime ambulatory ST segment changes and 14 patients with daytime and nocturnal angina and ST segment changes. Patients had ambulatory ST segment monitoring and exercise testing before and after operation and coronary arteriography was repeated in 34 patients after operation. Before operation, patients with daytime and nocturnal ischaemia tended to have more severe coronary artery disease, lower exercise tolerance, and more frequent ambulatory ST segment changes than those who had daytime ST segment changes only. After operation chest pain recurred in 22% of patients and ST segment depression during exercise testing or ambulatory ST segment monitoring recurred in 37% of the patients and was significantly more frequent in those with nocturnal ischaemia than in those with daytime ischaemia. Graft patency rates were similar in patients with and those without recurrence of ischaemia. After operation the frequency and magnitude of ST segment changes and exercise duration were improved in patients with preoperative daytime angina and also in those with daytime and nocturnal angina. The improvement was more pronounced in the latter groups. Thus, absence of postoperative angina is not a reliable indicator of the absence of reversible myocardial ischaemia. After revascularisation, patients with rest and nocturnal angina can expect relief from ischaemia, and if this recurs postoperatively, the threshold is improved and pain usually occurs only on exertion.     

Ischaemic threshold and haemodynamic changes during angina at rest in patients with unstable angina

To examine whether increases in heart rate might be a commontrigger of angina at rest, changes in heart rate, blood pressureand rate-pressure product during pain were compared with theischaemic threshold (heart rate with ST segment shift >=1 mm), determined by atrial pacing, in 272 patients with unstableangina. During an average of 5.9±5.2 episodes of angina,heart rate was comparable to control values (77.0±14.5vs 75.2±11.5, beats. min^–1, ns) and significantlylower than the ischaemic threshold (147.9±22.9, P <0.00001).The rate-pressure product was also lower (955±183 vs2033±369, x 10, P <0.00001). Heart rate during restangina was lower than the ischaemic threshold even when we consideredonly patients with ST depression during pain (n: 71, 81.4±16.0 vs 132.8±21.4, P<0.00001), those with three-vesseldisease (n: 43, 79.9±15.9 vs 136.9±22.0, P <0.00001), or those with a low ischaemic threshold (= <130beats. min, n: 78, 77.0±14.9 vs 118.3±10.7, P<0.00001).In 154 patients in whom a second pacing test was performed theresponse was reproducible in 137 cases (89%). Thus, heart rate barely changes during angina at rest in patientswith unstable angina and is consistently much lower than theischaemic threshold. These findings support the concept thatincreases in heart rate are an unlikely trigger of ischaemiaat rest, even in patients with markedly reduced coronary reserve.     

Comparison of cardiovascular response to combined static-dynamic effort, postprandial dynamic effort and dynamic effort alone in patients with chronic ischemic heart disease

The cardiovascular responses to combined static-dynamic effort, postprandial dynamic effort and dynamic effort alone were evaluated by upright bicycle ergometry during equilibrium-gated blood pool scintigraphy in 24 men, mean age 59 +/- 8 years, with chronic ischemic heart disease. Combined static-dynamic effort and the postprandial state elicited a peak cardiovascular response similar to that of dynamic effort alone; work load 643 +/- 156 and 638 +/- 161 vs 650 +/- 153 kg-m/min, respectively; heart rate 147 +/- 14 and 145 +/- 14 vs 143 +/- 17 beats/min; systolic pressure 195 +/- 26 and 200 +/- 25 vs 197 +/- 25 mm Hg; and rate-pressure product 286 +/- 48 and 292 +/- 55 vs 282 +/- 52. Heart rate, intraarterial systolic and diastolic pressures, rate-pressure product and ejection fraction were similar for the three test conditions at the onset of ischemia and at peak effort. The prevalence and extent of exercise-induced ischemic left ventricular dysfunction, ST-segment depression, angina pectoris and ventricular ectopic activity were also similar during the three test conditions. Direct and indirect measurements of systolic and diastolic blood pressure were highly correlated. The onset of ischemic ST-segment depression and angina pectoris correlated as strongly with heart rate alone as with the rate-pressure product during all three test conditions. The cardiovascular response to combined static-dynamic effort and to postprandial dynamic effort becomes more similar to that of dynamic effort alone as dynamic effort reaches a symptom limit. If significant ischemic and arrhythmic abnormalities are absent during symptom-limited dynamic exercise testing, they are unlikely to appear during combined static-dynamic or postprandial dynamic effort. This simplifies, the task of formulating guidelines for physical effort in patients with chronic ischemic heart disease, especially in providing "clearance" to perform avocational and vocational tasks involving combined static-dynamic and postprandial dynamic effort.     

Clinical significance of symptomatic and silent myocardial ischemia during exercise test in patients with effort angina pectoris--investigation of hemodynamic responses during supine ergometer exercise test

Thirty one patients with stable effort angina who had no prior myocardial infarctions underwent symptom-limited ergometer exercise test. Hemodynamic responses during exercise were assessed to determine whether or not the limiting symptoms were related to the severity of exercise-induced myocardial ischemia. Twenty-two subjects (Group I) were limited by angina and nine (Group II) were limited by other symptoms. There were no differences in age, sex distribution, prevalence of diabetes mellitus, and left ventricular ejection fraction between the two groups. Multivessel coronary artery diseases, however, were more frequent in group I (16/22 vs 3/9: p less than 0.05). Maximal work load (46.6 +/- 16.0 vs 62.5 +/- 13.4 W: p less than 0.05), exercise duration (4.7 +/- 2.0 vs 7.2 +/- 1.4 min: p less than 0.005), and maximal oxygen consumption (12.4 +/- 4.1 vs 19.3 +/- 3.3 ml/kg/min: p less than 0.005) were significantly lower in group I. The magnitude of ST depression was not different between the two groups (2.0 +/- 0.8 vs 1.8 +/- 0.7 mm: NS). At maximal exercise, heart rate, mean blood pressure, cardiac index, and stroke work index (SWI) were significantly lower in group I (p less than 0.05) and pulmonary capillary wedge pressure was significantly higher in group I (31.1 +/- 6.1 vs 25.1 +/- 5.6 mmHg: p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of myocardial revascularisation in patients with effort angina and those with effort and nocturnal angina.

The effects of coronary artery bypass graft operation were studied in 32 patients with daytime ambulatory ST segment changes and 14 patients with daytime and nocturnal angina and ST segment changes. Patients had ambulatory ST segment monitoring and exercise testing before and after operation and coronary arteriography was repeated in 34 patients after operation. Before operation, patients with daytime and nocturnal ischaemia tended to have more severe coronary artery disease, lower exercise tolerance, and more frequent ambulatory ST segment changes than those who had daytime ST segment changes only. After operation chest pain recurred in 22% of patients and ST segment depression during exercise testing or ambulatory ST segment monitoring recurred in 37% of the patients and was significantly more frequent in those with nocturnal ischaemia than in those with daytime ischaemia. Graft patency rates were similar in patients with and those without recurrence of ischaemia. After operation the frequency and magnitude of ST segment changes and exercise duration were improved in patients with preoperative daytime angina and also in those with daytime and nocturnal angina. The improvement was more pronounced in the latter groups. Thus, absence of postoperative angina is not a reliable indicator of the absence of reversible myocardial ischaemia. After revascularisation, patients with rest and nocturnal angina can expect relief from ischaemia, and if this recurs postoperatively, the threshold is improved and pain usually occurs only on exertion.     

The ischemic segment and left ventricular function during exercise angina

Improvement of the quality of transpulmonary left ventriculograms by exercise was demonstrated in 5 patients in a pre-study. In the main study transpulmonary left ventriculography was performed in 10 patients with coronary artery disease (CAD) at rest and during exercise, producing maximum angina pectoris (AP). Left ventricular pressure was recorded simultaneously. The extent of CAD, demonstrated in all patients by coronary angiography, was quantitated by a score. In the exercise ventriculograms, local wall motion was quantitated by 14 hemiaxes. During exercise AP, all patients developed wall motion abnormalities not present at rest. There was a significant linear correlation between coronary score and number of abmormally shortening hemiaxes (< 30% shortening) during exercise-AP (y = 0.16 × + 4.34; r = 0.933). The number of anormal hemiaxes correlated significantly (p < 0.05) with left ventricular enddiastolic pressure (LVEDP), dp/dt min, endsystolic volume index, enddiastolic volume index, ejection fraction, stroke work index, minute work, compliance SV/ Δ PD/ESV, and cardiac index. During exercise AP the extent of ischemic wall motion abnormalities is determined by localization and severity of coronary artery lesions. The extent of ischemic impairment of wall motion determines the severity of impairment of left ventricular pump function, filling pressure, and maximum speed of relaxation. Transpulmonary left ventriculography during exercise AP is a safe and relatively simple method to quantitate the extent of ischemic wall motion abnormalities. It could be useful in the selection of patients for coronary artery surgery and in the assessment of the results of this operation.     

Opposing effects of propranolol and diltiazem on the angina threshold during an exercise test in patients with syndrome X

Patients with angina pectoris, exercise induced myocardial ischemia, normal coronary arteries and no evidence of epicardial spasm, i.e. patients with syndrome x, have been suggested to haven inadequate increase in coronary blood flow during tachycardia, possibly due to a functional disorder of small coronary vessels. To evaluate the best medical management of this syndrome we studied 13 patients who showed the above set of findings. Patients were given propranolol (160 mg daily), diltiazem (360 mg daily) and placebo for 2 weeks, using a randomized single blind protocol. Upright bicycle ergometer testing was performed at the end of each period of treatment. Compared to placebo, diltiazem significantly (p less than 0.001) prolonged exercise duration (x +/- SD: 365 +/- 86 vs 303 +/- 89 sec) and time to onset of angina (358 +/- 88 vs 276 +/- 90 sec). Angina appeared in 7 patients with diltiazem vs 13 patients with placebo and occurred at a higher rate pressure product (26.3 +/- 3.5 vs 24.1 +/- 2.8 X 10(-3); p less than 0.02). Conversely, following propranolol exercise duration and time to onset of angina were unchanged and angina appeared in all patients at a lower rate pressure product (18.3 +/- 2.9 vs 24.4 +/- 3.6 X 10(-3); p less than 0.001). The most likely explanations for these findings are: propranolol counteracts beta 2-adrenergic receptors, thus further reducing coronary reserve. This may lower the anginal threshold; Diltiazem reduces smooth muscle tone in small coronary vessels. This may result in increased coronary reserve and exercise duration.     

Reproducibility of multistage graded exercise testing in patients with chronic stable angina

Exercise testing is widely used for the diagnosis of ischaemic heart disease and for the evaluation of antiaginal drugs. To assess reproducibility, analysis was carried out on 128 paired graded exercise tests from 103 patients performed at the same time of day and under identical conditions. Six different parameters were evaluated and compared between the basal test (no treatment) and the placebo test. During the basal period the mean (±SEM) exercise time to the development of angina was 6.0 (±0.2) min and the 1 mm ST depression time was 4.1 (±0.2) min. After 2 weeks of placebo the exercise time was 6.1 (±0.2) min (P = NS) and the 1 mm ST depression time was 4.2 (±0.2) min (P = NS). There was no significant difference between the resting or maximum heart rate on either test and the maximum ST segment depression (leads CM5 and CC5) was unaltered. In a second group of 17 patients where the basal tests were performed in the afternoon and the placebo tests in the morning, heart rate and ST segment were found to be reproducible but there was a significant difference in exercise time: 5.7 (±0.7) min for the basal test and 8.3 (±0.5) min for the placebo test (P < 0.001); and of the 1 mm ST depression time: 2.7 (±0.4) min for the basal test, and 5.4 (±0.5) min for the placebo test (P < 0.001).We conclude that exercise tests done under standardised conditions in the morning are highly reproducible in patients with chronic stable angina and therefore provide a valuable test for the evaluation of antianginal drugs.     

ST-segment fluctuation during treadmill exercise in patients with angina pectoris

The level of the ST-segment fluctuates transiently during treadmill exercise in some patients with angina pectoris. In the present study, the incidence and clinical significance of ST-segment fluctuation were studied before and after propranolol in 52 patients with angina pectoris. A transient greater than 0.5-mm (0.05 mV) upward shift of the ST-segment during a graded treadmill test was considered a significant fluctuation in leads without signs of previous myocardial infarction. The fluctuation was observed in three of 30 patients with rest or rest and effort angina pectoris before propranolol and in 14 of them after propranolol, while only one of 22 patients with effort angina alone showed fluctuation after the drug. Coronary arteriography revealed that in 15 patients showing ST-segment fluctuation with propranolol, seven patients had no significant coronary stenosis, six had one-vessel disease and two had two-vessel disease. In 24 patients with documented coronary artery spasm, ST-segment fluctuation was induced in two (8%) before propranolol and in 13 (54%) after propranolol. Our results suggest that ST-segment fluctuation during graded treadmill exercise may be related to transient coronary vasospasms exacerbated by propranolol.     

Comparison of cardiovascular responses to static-dynamic effort and dynamic effort alone in patients with chronic ischemic heart disease.

Thirty men, mean age 55 years, known to have treadmill-induced ischemic ST-segment depression, performed static and dynamic effort, i.e., forearm lifting and treadmill exercise, separately and combined. Static effort was sustained at 20%, 25% or 30% of maximal forearm lifting capacity. Two symptom-limited treadmill tests, one with and one without added static effort, were performed on each of two visits. Compared with dynamic effort alone, combined static-dynamic effort decreased treadmill work load and increased heart rate, systolic blood pressure and rate-pressure product at the onset of ischemic ST-segment depression or angina pectoris: 7.1 +/- 0.4 vs 8.0 +/- 0.5 (SEM) multiples of resting oxygen consumption (mets), estimated; 141 +/- 3 vs 134 +/- 3 beats/min; 170 +/- 4 vs. 162 +/- 4 mm Hg and 239 +/- 8 vs 218 +/- 9 (p less than 0.001). The prevalence of angina pectoris was significantly less with combined static-dynamic effort than with dynamic effort alone. Static effort causes a resetting of the threshold at which ischemic abnormalities appear during dynamic effort.     

Alterations in angina threshold with nifedipine during pacing induced angina

Changes in coronary haemodynamics and angina threshold were determined during atrial pacing in 11 patients with fixed obstructive coronary artery disease with effort angina before and after the administration of 20 mg of oral nifedipine. Coronary vascular resistance decreased at resting and at "subangina" heart rates but not at "angina" rates. Primary coronary vasodilatation with nifedipine was also suggested by higher coronary sinus oxygen content whether at rest or at subangina or angina heart rates. After nifedipine angina occurred at a lower double product and lower myocardial oxygen consumption. These findings suggest that nifedipine is a coronary vasodilator, but angina can occur at a lower angina threshold in some patients with obstructive coronary artery disease.