Exercise-induced Myocardial Ischemia In Patients Research Articles

Incremental Value of a Single High-sensitivity Cardiac Troponin I Measurement to Rule Out Myocardial Ischemia

BackgroundThe aim of this study was to investigate the value of a novel high-sensitivity cardiac troponin I measurement to rule out exercise-induced myocardial ischemia in patients without known coronary artery disease. MethodsWe included 714 patients without previously known coronary artery disease who were referred for rest/stress myocardial perfusion single photon emission tomography. All clinical information available to the treating cardiologist was used to quantify the clinical judgment regarding the presence of exercise-induced myocardial ischemia using a visual analogue scale twice: once before and once after bicycle exercise stress testing. High-sensitivity cardiac troponin I measurements were obtained before stress testing in a blinded manner. The presence of exercise-induced myocardial ischemia was adjudicated on the basis of myocardial perfusion single photon emission tomography combined with coronary angiography findings. ResultsExercise-induced myocardial ischemia was detected in 167 participants (23.4%). High-sensitivity cardiac troponin I levels were significantly higher in patients with exercise-induced myocardial ischemia (4.0 ng/L [95% confidence interval, 2.8-8.6] vs 2.6 ng/L [95% confidence interval, 1.8-4.1], P < .001) and remained an independent predictor of ischemia in multivariable analysis (P < .001). Combining clinical judgment before exercise testing with high-sensitivity cardiac troponin I levels increased diagnostic accuracy as quantified by the area under the receiver operating curve from 0.64 to 0.73 (P < .001), which also tended to be superior to clinical judgment after exercise testing (0.69, P = .056). A single resting high-sensitivity cardiac troponin I measurement provided similar diagnostic accuracy as integrated clinical judgment after exercise testing including work load, as well as symptoms and electrocardiogram changes (0.70 vs 0.69, P = not significant). ConclusionsHigh-sensitivity cardiac troponin I measurements seem to complement noninvasive clinical assessment in patients with suspected coronary artery disease.

A comparison of the diagnostic performance of the ST/HR hysteresis with cardiopulmonary stress testing parameters in detecting exercise-induced myocardial ischemia

Because ST segment depression has limited diagnostic performance at exercise electrocardiography (ECG), ST segment depression/heart rate (ST/HR) hysteresis and cardiopulmonary exercise test (CPET)-derived parameters have been proposed as alternatives to diagnose exercise-induced myocardial ischemia. We compared the diagnostic performance of such parameters. We studied 56 subjects (45 men, 11 women, age 59.7 ± 13.6 years) referred for suspected exercise-induced myocardial ischemia with an equivocal ECG exercise test. All subjects serially underwent CPET and a myocardial single-photon emission computerized tomography (SPECT) perfusion imaging (as the gold standard for ischemia). Maximum ST depression at peak exercise (ST-max), the ST/HR hysteresis, ΔVO2/ΔWR b-b1 slope, ΔVO2/ΔWR (aa1-bb1), VO2/HR flattening duration and other CPET parameters were derived in all subjects. On the basis of SPECT, 23 subjects (41%) were considered ischemic and 33 subjects (59%) non-ischemic. ST/HR hysteresis was higher (0.026 mV; 95% CI: 0.003 to 0.049 vs -0.016 mV; 95% CI: -0.031 to -0.001 mV) and ST-max was lower (-0.105 mV; 95% CI: -0.158 to -0.052 vs 0.032 mV; 95% CI: -0.001 to -0.066 mV) in ischemic vs non-ischemic subjects (P=0.004 and P=0.001, respectively). Among CPET parameters, ΔVO2/ΔWR b-b(1) slope was lower (9.4 ± 3.8) and ΔVO2/ΔWR (aa(1)-bb(1)) was higher (2.1 ± 2.6) in ischemic vs non-ischemic subjects (11.4 ± 2.3, P=0.005, and 1.1 ± 1.5, P=0.001, respectively). The ST/HR hysteresis had the highest area under the curve value, better (P<0.05) than any other parameters tested, thus showing the highest overall diagnostic performance. The ST/HR hysteresis is superior to CPET-derived parameters for detecting exercise-induced myocardial ischemia in patients with equivocal ECG exercise test results.

Elevated baseline hs-cTnT levels predict exercise-induced myocardial ischemia in patients with peripheral arterial disease

IntroductionDue to the systemic nature of atherosclerosis, the prevalence of coronary artery disease (CAD) is high in patients with peripheral arterial disease (PAD). A biochemical assay for assessing cardiac risk might improve clinical evaluation of PAD patients. The aim of this study was to investigate whether a new high-sensitivity cardiac Troponin T (hs-cTnT) assay can predict exercise-induced myocardial ischemia in PAD patients without clinical signs of CAD. MethodsSixty-eight ambulatory patients with Fontaine stage II PAD underwent treadmill stress testing to maximum walking distance. Myocardial ischemia was assessed using a 2-lead Holter ECG and ST-segment depression of ≥0.2mV was considered significant. Hs-cTnT was measured from serum samples taken at baseline as well as 5, 10 and 30min after exercise. ResultsHs-cTnT baseline levels were significantly higher (19.3ng/L (5.0; 20.2ng/L) vs. 6.6ng/L (4.4; 9.4ng/L); p=0.037) and increase of serum levels 5min after cessation of exercise was more pronounced (1.09ng/L (0.23; 1.80ng/L) vs. 0.22ng/L (−0.1; 0.65ng/L), p=0.032) in ECG positive patients compared to individuals with normal ECG. Logistic regression analysis identified the baseline hs-cTnT serum level as an independent risk factor for developing significant exercise-induced ST-segment depression (odds ratio 1.2 per 1-unit increase, p=0.015). ConclusionsIn patients with PAD, exercise-induced myocardial ischemia is associated with elevated baseline levels and a significant early increase of hs-cTnT serum levels.

A randomised controlled trial of the effect of high concentration oxygen on myocardial ischaemia during exercise

BackgroundInternational guidelines recommend the use of oxygen for angina, based on Level C evidence. We aimed to determine whether high concentration oxygen influences the time to exercise-induced ischaemia or angina in patients with stable ischaemic heart disease (IHD). Methods22 subjects with IHD and a positive exercise treadmill test (ETT) awaiting coronary angiography were randomised to two further ETTs according to a double-blind, crossover study design, during which they breathed oxygen or air at 15L/min via a non-rebreather mask. Subjects in whom significant coronary artery disease was not subsequently confirmed by coronary angiography were excluded from analysis. The primary outcome was time to exercise-induced myocardial ischaemia, defined as ≥1mm ST depression on contiguous electrocardiographic (ECG) leads. The secondary outcome was time to onset of angina. ResultsExercise-induced myocardial ischaemia occurred in 17 of the 19 subjects with coronary artery disease, with the remaining two stopping due to shortness of breath. The mean (SD) time to inducible ischaemia was 35 (47) s longer (95% CI 11 to 59, P=0.007) with oxygen compared to air. Exercise-induced angina occurred in 9 subjects and started a mean 19 (32) s later (95% CI −6 to 43, P=0.12) with oxygen compared to air. All subjects who developed myocardial ischaemia or angina did so during both of the study ETTs. ConclusionHigh concentration oxygen increases the time to onset of exercise-induced myocardial ischaemia in patients with stable IHD.

Effects of exogenous metabolic substrate modulation on exercise-induced myocardial ischemia

The aim of the study is to compare the impact of intravenous glucose versus lipid versus saline on exercise-induced myocardial ischemia in patients with stable angina. Twelve men with coronary artery disease and positive exercise tests performed a symptom-limited, modified Bruce electrocardiogram (ECG) exercise test at 3 sessions, 3 weeks apart. They randomly received, in double-blind design, at each session equal intravenous volumes of 10% glucose/insulin or Intralipid plus heparin or saline. We assessed the effects on (1) ischemic threshold (heart rate x systolic pressure at 1-mm ST-segment depression [STD]) and (2) maximum ST-depression (Max STD) corresponding to the highest heart rate x systolic pressure common to the 3 tests. During glucose infusion, glycemia increased from 5.7 +/- 0.4 to 9.4 +/- 3.0 mmol/L but did not change during lipid or saline infusion. During lipid infusion, free fatty acids increased from 0.32 +/- 0.19 to 1.44 +/- 0.46 mmol/L but decreased during glucose infusion from 0.39 +/- 0.21 to 0.04 +/- 0.03 mmol/L and did not change during saline. Exercise times were 10.0 +/- 3.4, 9.8 +/- 3.4, and 10.3 +/- 3.5 minutes, during glucose, lipid, and saline infusions, respectively. Ischemic thresholds (x 10(-3)) were 16.5 +/- 2.8, 16.8 +/- 2.7, and 16.6 +/- 2.6, respectively. MaxSTD was 2.5 +/- 1.4, 2.5 +/- 1.0, and 2.5 +/- 1.0 mm, respectively. Neither glucose-insulin nor lipid infusion modified exercise ischemic parameters compared with saline control, suggesting that marked and acute changes in exogenous energy substrate are unlikely to affect exercise-induced myocardial ischemia.

Can prolonged exercise-induced myocardial ischaemia be innocuous? reply

We appreciate Dr Fragasso's interest in our recent work.1 Fragasso et al. 2 showed in patients with coronary disease a lowered left ventricular filling rate 2 days after exercise that was no longer significantly different from baseline at 7 days. Whether this is sufficient to support the notion that exercise-induced myocardial ischaemia in patients with stable coronary artery disease causes sustained clinically significant diastolic dysfunction cannot be certain. Importantly, the 15 patients in Dr Fragasso's study had severe coronary disease as evidenced by …

Effect of Losartan in Treatment of Exercise-Induced Myocardial Ischemia

Because no controlled clinical studies are available about the possible role of angiotensin II receptor blockers in preventing effort myocardial ischemia, we evaluated the effect of angiotensin II receptor blocker/losartan in preventing exercise-induced myocardial ischemia in patients with coronary artery disease. Twenty-four sedentary patients with chronic stable ischemia were prospectively randomized to 28 days (double blind) of losartan 100 mg or losartan placebo in 2 divided doses. In each patient the treatment was crossed over to the alternative regimen (28 days, double blind) after a 1-week placebo period (single blind). At the end of each phase a new exercise stress test was performed. At baseline, systolic blood pressure was significantly decreased after losartan 100 mg compared with losartan placebo. At submaximal exercise, systolic blood pressure and rate-pressure product were lower after losartan 100 mg administration compared with losartan placebo, and these findings remained significant at 1-mm ST depression and at peak exercise. Losartan 100 mg administration versus losartan placebo significantly delayed the time to 1-mm ST-depression onset and decreased ST-segment depression at peak exercise and time to recovery of ST-segment depression. Losartan 100 mg administration compared with losartan placebo was able to significantly increase exercise duration and maximal workload during exercise stress testing. In conclusion, in our study, losartan decreased electrocardiographic parameters of myocardial ischemia in patients with coronary artery disease, suggesting a possible role of this drug in treatment of patients with effort myocardial ischemia.

Arterial stiffness as a risk factor for coronary atherosclerosis

The major pathophysiologic process of coronary atherosclerosis is a defect or injury of the arterial endothelial function. The rate of progression of coronary atherosclerosis is highly variable and mainly determined by risk contributors such as lipids, glucose, and smoking. Coronary plaque rupture is the precipitating factor for clot formation and acute coronary events. Measurement of arterial stiffness with different noninvasive techniques provides information about the functional and structural vascular changes at the level of the aorta, muscular conduit arteries, the peripheral branches, and the microvascular components. Arterial stiffness has been related to the Framingham and other cardiovascular risk scores. Large artery stiffness contributes to exercise-induced myocardial ischemia in patients with coronary artery disease. It can predict the outcome after coronary interventions. There is now evidence that arterial stiffness is a predictor for cardiovascular events in the general population, in patients with hypertension, end-stage renal disease, impaired glucose intolerance, and coronary artery disease. Future studies are warranted to demonstrate the value of follow-up of arterial stiffness as a marker of reduction of arterial wall damage during antihypertensive, antidiabetic, and lipid-lowering therapy. Promising study results show that measurement of arterial stiffness could become an important part of the routine assessment of patients in daily practice.

What is the plausible strategy for the management of patients with isolated coronary artery ectasia and myocardial ischemia?

I have recently read with great interest an important article published in International Journal of Cardiology entitled “The changes of fractional flow reserve (FFR) after intracoronary nitrate and nicorandil injection in coronary artery ectasia (CAE)” [1]. In this article, Kim et al. [1] have evaluated FFR in patients with isolated CAE in response to intracoronary nitrate and nicorandil injection. Baseline value of FFR has been shown to be within normal range in patients with isolated CAE. It has also been found that intracoronary nitrate and nicorandil injection has no significant effect on FFR. Previously, epicardial coronary dilation has been suggested to exacerbate myocardial ischemia [2] and are discouraged in patients with isolated CAE. Although the data reported by Kim et al. [1] have shown that coronary vasodilators as nitrate and nicorandil have no detrimental effect on coronary blood flow, the small sample size (only 10 patients with isolated coronary artery ectasia) limits extrapolation of these findings to all patients with isolated CAE. Kruger et al. [2] have documented the presence of angina, positive exercise stress test and pacing-induced myocardial ischemia in patients with isolated CAE. In addition, Sayin et al. [3] have also reported the presence of exercise-induced myocardial ischemia in patients with CAE without obstructive coronary artery disease. Furthermore, acute coronary syndromes may also develop in these patients despite the

Effect of atorvastatin on exercise-induced myocardial ischemia in patients with stable angina pectoris

To investigate whether marked and sustained lipid-lowering in subjects with stable angina pectoris and dyslipidemia reduces exercise-induced myocardial ischemia, 17 subjects were treated with dose-adjusted atorvastatin over 1 year and underwent serial evaluation of exercise electrocardiographic ischemic parameters, serum biomarkers, and brachial artery endothelial function. Endothelial function improved progressively and C-reactive protein, P-selectin, and tissue plasminogen activator inhibitor levels decreased, but there was no decrease in exercise electrocardiographic ischemia.

Effect of homocysteine-lowering therapy on vascular endothelial function and exercise performance in coronary patients with hyperhomocysteinaemia

Objective — This study was performed to determine the effect of homocysteine-lowering therapy (HLT) on endothelium-dependent vasodilation (EDD) and exercise performance in patients with coronary artery disease.Methods and Results — Among the patients who were on the waiting list for coronary intervention, 26 male patients (plasma homocysteine (Hcy) levels >15 mol/l) who had a focal stenosis of at least 70% in the left anterior descending artery were included in the study.The patients were matched to receive HLT (n = 15; 0.4 mg of folic acid, 2 mg vitamin B6 and 6 g of vitamin B12) or placebo (n = 11) until the coronary intervention was performed (mean 3.8±0.9 weeks). Brachial artery vasomotion test and treadmill stress testing were performed at baseline and 4 weeks after HLT before the time of coronary intervention in each patient. Hcy levels were found to be decreased significantly after HLT compared to baseline (23.4±6 vs. 11.3±4 mol/l; p<0.001) whereas placebo had no effect. HLT but not placebo produced a marked improvement in EDD, from 3.9±1.1% to 9.4±2.3% (p<0.0001). Endothelium-independent nitroglycerin-induced dilation was similar in the HLT and placebo groups compared with the baseline. In the exercise testing, HLT resulted in a significant improvement in exercise duration and reduction in the amount of maximal ST-segment depression, (from 6.5±2 to 6.9±2 min, p = 0.02 and from 1.2±0.7 to 0.8±0.5 mm, p = 0.01, respectively) whereas placebo did not.Conclusion — Lowering Hcy levels improves EDD and exercise performance while reducing the exercise-induced myocardial ischaemia in patients with coronary heart disease and hyperhomocysteinaemia.

Beneficial effects of betaxolol, a selective antagonist of beta-1 adrenoceptors, on exercise-induced myocardial ischemia in patients with coronary vasospasm

Although beta-blockers can not be used for the treatment of vasospastic angina, the effect of beta-blockers with vasorelaxant property on coronary vasospasm remains uncertain. In this study, we evaluated the effect of betaxolol, a new beta-blocker with calcium antagonistic property, as an additional therapy on vasospastic angina (VSA) with anginal attacks on effort. We enrolled 12 patients with VSA and anginal attacks with ST segment depression during exercise stress test. All patients received 1.25–5 mg of betaxolol for 3 months. Treadmill exercise stress test and adenosine triphosphate stress thallium-201 myocardial scintigraphy were performed before and 3 months after the onset of the betaxolol treatment. The other drugs including calcium antagonists, nitrates and nicorandil were continued. No patients experienced the exacerbation of angina during the betaxolol treatment. Exercise time to chest pain (317.5±72.1–454.2±75.5 s, P<0.01) and maximal ST segment depression (1.67±0.67–1.16±0.46 mm, P<0.01) obtained by exercise stress test, the defect score (8.6±2.7–5.3±2.1, P<0.01), the extent score (14.8±5.8–8.8±4.6%, P<0.01), the severity score (17.5±7.3–11.3±5.2, P<0.01) and washout rate (31.4±5.6–37.6±5.0%, P<0.01) obtained by the scintigraphy were improved by betaxolol. Our results suggest that betaxolol increases regional myocardial blood flow and improves exercise capacity in patients with VSA. Betaxolol may become a drug for a new potential therapy for VSA.

Large artery stiffness predicts ischemic threshold in patients with coronary artery disease

ObjectivesThe goal of this study was to determine whether large artery stiffness contributes to exercise-induced myocardial ischemia in patients with coronary artery disease (CAD). BackgroundLarge artery stiffness is an independent predictor of cardiovascular mortality and a major determinant of pulse pressure and, thus, cardiac afterload and coronary perfusion. Clinical relevance of the hemodynamic consequences of large artery stiffening has not previously been demonstrated in relation to myocardial ischemia. MethodsWe hypothesized that stiffer large arteries would reduce myocardial ischemic threshold as assessed by time to ST-segment depression of 0.15 mV during a treadmill exercise test in patients with CAD. Ninety-six patients with CAD (78 men) age 62 ± 9 years (mean ± SD) were classified as having single (52 patients), double (31 patients), or triple (13 patients) coronary vessel disease, based on angiographically confirmed stenoses >50%. Systemic arterial compliance, distensibility index, aortic pulse wave velocity, and carotid augmentation index were measured using carotid applanation tonometry and Doppler velocimetry of the ascending aorta, at rest. ResultsIn univariate analysis, all large artery stiffness/compliance indexes correlated with time to ischemia (p = 0.01 to 0.009). Both carotid (p = 0.007) and brachial (p = 0.001) pulse pressure also correlated inversely with time to ischemia. In multivariate analysis including other major risk factors plus severity of coronary stenosis, indexes of arterial stiffness were significant independent predictors of ischemic threshold. ConclusionsWithin a patient group with moderate CAD, large artery stiffness was a major determinant of myocardial ischemic threshold.

Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases.

Rho-kinase has been identified as one of the effectors of the small GTP-binding protein Rho. Accumulating evidence has demonstrated that the Rho/Rho-kinase-mediated pathway plays an important role in various cellular functions, not only in vascular smooth muscle contraction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expressions, all of which may be involved in the pathogenesis of arteriosclerosis/atherosclerosis. Indeed, animal experiments have demonstrated that Rho-kinase inhibitors effectively suppress coronary artery spasm and that long-term inhibition of Rho-kinase inhibits the development of coronary arteriosclerotic lesions and even causes regression of coronary vascular lesions in vivo. Recent clinical studies also have demonstrated the inhibitory effect of a Rho-kinase inhibitor on coronary artery spasm in patients with vasospastic angina and on exercise-induced myocardial ischemia in patients with stable effort angina with adequate safety. It is possible that Rho-kinase is also involved in the pathogenesis of other forms of cardiovascular diseases. Thus, Rho-kinase could be regarded as a novel therapeutic target in treatment of cardiovascular diseases.

Exercise-induced myocardial ischemia in patients with coronary artery ectasia without obstructive coronary artery disease

Background: Aetiology, clinical significance and treatment options for coronary artery ectasia/aneurysm is not clear. Objective: We sought to determine whether exercise can induce coronary ischemia in patients with coronary artery ectasia/aneurysm without significant coronary stenosis. Methods: Coronary artery ectasia was defined as 1.5–2-fold, aneurysm as >2-fold luminal dilatation of the adjacent normal segment. The study patients could have irregularities with ectatic coronaries but they did not have stenotic lesions >50% with visual assessment of two blinded observers. Patients having coronary artery ectasia or aneurysm with prior myocardial infarction, dilated cardiomyopathy, valvular heart disease, bundle branch block, significant ST-T changes were excluded. The control group was formed from a well matched population of 32 patients with normal coronary arteries who have not performed a treadmill test before coronary angiography. The study group underwent a symptom limited treadmill test if they did not have one before coronary angiogram, all control patients underwent treadmill test. Results: Thirty-three patients with coronary artery ectasia/aneurysm (ranging from one to three vessels) but without significant stenosis were derived from 4470 cardiac catheterization procedures between January 1998 and July 2000. In the study group, 17 of the patients had positive treadmill tests with respect to five patients in the control group ( P=0.004). In subgroup analysis, diffuse ectasia/aneurysm (involving 2–3 vessels) was found to be strongly related with ischemia ( P=0.005) with respect to local disease. Conclusion: Coronary artery ectasia/aneurysm may lead to exercise induced ischemia, especially in the diffuse form.

Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade

OBJECTIVESWe sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia.BACKGROUNDAlthough angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease.METHODSWe studied 43 patients (average age 63 ± 8 years) with exercise-induced myocardial ischemia (≥0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo-controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made after three weeks (short-term) and 12 weeks (long-term).RESULTSAt baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate × systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 ± 1.9 min) but was unchanged in the placebo group (4.4 ± 1.3 min; p < 0.05 between groups). In contrast, RPP was not affected. Concentrations of both atrial and brain natriuretic peptides at peak exercise tended to be lower by enalapril, if compared to placebo (p = NS).CONCLUSIONSAngiotensin-converting enzyme inhibition may reduce exercise-induced myocardial ischemia in patients with normal left ventricular function. Further studies are needed to elucidate the mechanisms involved.

Effects of the repeated administration of adenosine and heparin on myocardial perfusion in patients with chronic stable angina pectoris

The mechanism by which ischemia stimulates angiogenesis is unknown. Adenosine is released during myocardial ischemia and may be a mediator of this process. Experimental data suggest that heparin may enhance this effect. The purpose of this open-labeled, placebo-controlled trial was to determine whether repeated intravenous administration of adenosine and heparin could mimic physiologic angiogenesis and reduce the amount of exercise-induced myocardial ischemia in patients with coronary artery disease. Subjects with chronic stable angina refractory to conventional medical therapy and not suitable for revascularization received either adenosine (140 μg/kg/min for 6 minutes) and heparin (10,000 U bolus), (n = 14), or placebo, (n = 7) daily for 10 days. All patients underwent baseline and follow-up exercise testing with thallium-201 single-photon emission computed tomography myocardial perfusion imaging. A semiquantitative assessment of the extent and severity of the perfusion abnormalities was calculated by 2 blinded investigators. There was no significant change in exercise duration or in the peak heart rate systolic blood pressure product associated with adenosine and heparin compared with placebo treatment. There was, however, a 9% reduction in the extent (60.6 ± 4.0 vs 54.9 ± 4.1, p = 0.03) and a 14% improvement in severity (41.5 ± 3.2 vs 35.7 ± 2.9, p = 0.01) of the myocardial perfusion abnormalities seen in patients who received adenosine and heparin compared with placebo. Thus, in this pilot study, repeated administration of adenosine and heparin reduced the amount of exercise-induced ischemia in patients with chronic stable angina refractory to conventional treatment.

Clinical Implications of Silent Versus Symptomatic Exercise-Induced Myocardial Ischemia in Patients With Stable Coronary Disease

Objectives. This study was undertaken to better understand the functional and prognostic significance of silent relative to symptomatic ischemia.Background. Previous studies have reached conflicting conclusions as to whether painless ischemia identified during noninvasive cardiac testing is related to a lesser extent of myocardial ischemia or a different prognosis than ischemia accompanied by angina, or both.Methods. Nine hundred thirty-six clinically stable patients 1 to 6 months after an acute coronary event, either myocardial infarction or unstable angina, underwent ambulatory monitoring, exercise treadmill testing and stress thallium-201 scintigraphy. They were then followed up prospectively for a mean of 23 months for recurrent cardiac events (cardiac death, nonfatal myocardial infarction or unstable angina).Results. Compared with patients with symptomatic ischemia during testing (n = 125), those with silent ischemia (n = 378) demonstrated less severe and extensive reversible defects on stress thallium scintigraphy (p = 0.0008), less functional impairment during treadmill testing manifested by longer exercise duration (640 ± 173 vs. 529 ± 190 s, p = 0.002) and longer time to ST segment depression (530 ± 215 vs. 419 ± 205 s, p = 0.0001) and less frequent ST segment depression during ambulatory monitoring (9% vs. 19%, p = 0.005). Patients with symptomatic ischemia had a significantly (p = 0.004) increased number of subsequent recurrent cardiac events (28.8%) versus those with silent (18.0%) or no (17.3%) ischemia. Adverse outcomes were especially concentrated in the subgroup with symptomatic ischemia and poor exercise tolerance. The difference in cardiac event rates between patients with silent versus symptomatic ischemia persisted after adjustment for baseline clinical characteristics by Cox regression analysis.Conclusions. Patients with painless ischemia during exercise testing 1 to 6 months after recovery from a coronary event have less jeopardized ischemic myocardium and fewer recurrent cardiac events than patients with symptomatic ischemia.(J Am Coll Cardiol 1997;29:756–63)

Diastolic Time During Exercise-Induced Myocardial Ischemia in Patients With Myocardial Infarction

The relation between diastolic time and myocardial perfusion defect redistribution of the infarct-related region was studied during upright bicycle exercise with thallium-201 scintigraphy in 37 patients with recent anterior myocardial infarction. In addition to the higher incidence of residual stenosis of the infarct-related artery, a disproportionate shortening of diastolic time in patients with myocardial perfusion defect redistribution permitted further reduction of subendocardial blood flow during exercise.

Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment

Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after sustained isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, the efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1 % (p = 0.03), the time to 1 mm ST-segment depression by 19% (p < 0.01), and the maximal ST-segment depression by 33% (p = 0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p < 0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50 mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.