Effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation in the coronary circulation

The effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation was investigated in seven patients with severe proximal lesions of the left anterior descending coronary artery to determine if acute ischemia activates the coagulation system. Fibrin formation was assessed from plasma levels of fibrinopeptide A. Platelet activation was assessed by levels of platelet factor 4, beta-thromboglobulin and thromboxane B2. Plasma levels were measured before, during and after acute myocardial ischemia induced by rapid atrial pacing. Blood samples were collected from the ascending aorta and from the great cardiac vein through heparin-bonded catheters. The occurrence of anterior myocardial ischemia was established by electrocardiography and by myocardial lactate extraction. No significant transmyocardial gradients in the levels of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 were found at rest, during ischemia or in the recovery period, and levels in the great cardiac vein did not change in response to ischemia. These data indicate that pacing-induced myocardial ischemia does not result in release of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 into the coronary circulation, and imply that acute ischemia does not induce platelet activation or fibrin formation in the coronary circulation.     

Effects of a selective thromboxane synthetase inhibitor (OKY-046) in patients with coronary artery disease during exercise

We studied the levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), platelet aggregability, beta-thromboglobulin and platelet factor 4 in 30 coronary artery disease (CAD) patients and 21 normal subjects during exercise. During treadmill exercise, 13 of 30 CAD patients reported chest pain. We administered a selective thromboxane synthetase inhibitor (OKY-046) for 2 weeks to 10 CAD patients with exercise-induced chest pain and studied its effects. At rest, the plasma TXB2 levels and platelet aggregation were significantly lower in normal subjects than in CAD patients, and there was no difference between CAD patients with and without exercise-induced chest pain. On treadmill testing, plasma TXB2 levels and platelet aggregation increased significantly only in the CAD patients with exercise-induced chest pain. Plasma 6-keto-PGF1 alpha levels in normal subjects were significantly higher than those in CAD patients both at rest and during exercise. After administration of OKY-046, mean exercise time increased significantly from 7.5 to 8.6 min (p less than 0.001). Plasma TXB2 level and platelet aggregation decreased significantly after OKY-046 administration both at rest and during exercise. These results suggest that a marked increase in TXA2, with only a minimal change in PGI2, during exercise may contribute to exercise-induced myocardial ischemia, and that OKY-046 is useful in the treatment of CAD patients.     

Fibrinopeptide A and platelet factor levels in unstable angina pectoris

Fibrinopeptide A, platelet factor 4, beta-thromboglobulin, thromboxane B2, and 6-keto-prostaglandin F1 alpha were estimated by radioimmunoassay on venous plasma samples taken within 48 hr of admission from 16 consecutive patients with unstable angina and 15 patients with stable angina matched for clinical variables. The ratio of circulating platelet aggregates, platelet aggregation to increasing concentrations of ADP (0.455 to 1.82 micrograms/ml), and platelet thromboxane B2 production in vitro were also tested. The two groups of patients were statistically similar in terms of sex distribution, age, presence of risk factors, use of medication, extent of coronary artery disease and history of previous myocardial infarction. Mean plasma levels of fibrinopeptide A were 2.7 +/- 0.4 ng/ml (geometric means +/- SEM, range 1.5 to 5.5) in patients with stable angina vs 5.5 +/- 1.8 ng/ml (range 2.4 to 32; p less than .001) in those with unstable angina. In the latter group, after 6 to 8 days, fibrinopeptide A levels decreased to 3.6 +/- 0.5 ng/ml (range 1.5 to 9.3; p less than .04 vs admission). All other variables measured were statistically identical in the two groups. We conclude that plasma fibrinopeptide A levels, as opposed to platelet factors, discriminate between patients with unstable and stable angina, indicating an activation of the coagulation system in unstable angina.     

Fibrinopeptide A, platelet factor 4, and beta-thromboglobulin levels in coronary heart disease

In vivo platelet alpha-granule release and fibrin I formation were measured in 82 patients with ischemic heart disease by radioimmunoassay of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A. The presence and extent of coronary artery disease were determined by coronary arteriography, and the extent of left ventricular regional dysfunction was assessed by contrast left ventriculography. In patients with abnormal coronary arteriograms without previous myocardial infarction, mean levels of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A were not elevated. In patients in whom myocardial infarction had occurred more than 6 mo previously, platelet factor 4 (8.3 ng/ml; p less than 0.01) and beta-thromboglobulin (33.2 ng/ml; p less than 0.001) levels were significantly elevated, but fibrinopeptide A levels were normal. Levels of platelet factor 4 and beta- thromboglobulin were unrelated to the extent of coronary artery disease. In the patients with prior infarction, beta-thromboglobulin correlated directly with extent of left ventricular regional dysfunction (r = 0.53; p less than 0.01) and inversely with ejection fraction (r = -056; p less than 0.05). In a small group of patients with left ventricular aneurysm, mean fibrinopeptide A levels were also elevated. We interpret these findings as indicating that platelet release in patients with ischemic heart disease results from platelet reaction with previously infarcted myocardium rather than with the atherosclerotic coronary arteries.     

Evaluation of thromboxane production and complement activation during myocardial ischemia in patients with angina pectoris

BACKGROUND. The complement system and arachidonic acid metabolites are involved in severe myocardial ischemia such as myocardial infarction. Furthermore, there is experimental evidence for C5a participation in thromboxane production. METHODS AND RESULTS. We examined whether C5a and thromboxane are produced during brief and reversible episodes of myocardial ischemia induced in patients with stable angina. Twenty-five patients underwent either atrial pacing or percutaneous transluminal coronary angioplasty associated with arterial and coronary sinus blood sampling. Rapid atrial stimulation of patients with effort angina caused significant ST segment depression (delta ST = -1.7 +/- 0.2 mm), decreased fractional lactate extraction (from +12.8 +/- 2.5% baseline to -13.7 +/- 4.6% at peak ischemia, n = 13, p less than 0.001), and increased coronary sinus plasma thromboxane B2 levels (from 345 +/- 85 pg/ml baseline to 1,684 +/- 64 pg/ml at peak ischemia, p less than 0.01). Changes of fractional lactate extraction correlated significantly with changes of coronary sinus plasma levels of thromboxane B2. There was no change of coronary sinus 6-keto-PGF1 alpha levels. Similar pacing of control subjects (n = 6) did not cause release of lactate or thromboxane. Seventeen other patients underwent exercise testing with noninvasive measurements of thromboxane and prostacyclin metabolites in urinary samples collected before and after the test. No detectable increase of urinary 11-dehydrothromboxane B2 was measured in patients with stable angina after exercise-induced myocardial ischemia. However, basal 11-dehydrothromboxane B2 levels were significantly higher in patients with angina (105 +/- 25 pg/mmol creatinine, n = 9) than in control patients (45 +/- 8 pg/mmol creatinine, n = 8, p less than 0.05 between groups). Coronary sinus plasma levels of the anaphylatoxin C5a always remained below 4 ng/ml in patients undergoing pacing. More severe myocardial ischemia after coronary angioplasty (percent lactate extraction decreased from +24.8 +/- 2.7% baseline to -41.6 +/- 22.4% at peak ischemia, p less than 0.05) was not associated with C3a or C5b-9 generation. In all patients, there was neither platelet sequestration nor platelet alpha-granule release (no changes of beta-thromboglobulin/platelet factor 4 levels) into the coronary sinus plasma. CONCLUSIONS. Patients with stable angina have chronically increased thromboxane synthesis as assessed by excretion of urinary metabolites. Thromboxane is acutely released into the coronary sinus during pacing-induced ischemia without significant intracoronary platelet aggregation. Complement does not appear to be activated in stable angina during brief and reversible episodes of myocardial ischemia and does not contribute to thromboxane production.     

Thromboxane release in coronary artery disease: spontaneous versus pacing-induced angina

To determine thromboxane A2 release in coronary artery disease, we measured its stable metabolite thromboxane B2 by radioimmunoassay in 20 patients. In 15 patients with stable disease (last angina episode greater than 96 hours before study), coronary venous thromboxane B2 concentrations were lower than in aortic blood (mean 109 +/- 36 vs 194 +/- 40 pg/ml, p less than 0.001). In contrast, in five other patients with spontaneous angina, coronary venous thromboxane B2 concentrations were higher than aortic thromboxane B2 concentrations during the angina episode (mean 1716 +/- 316 vs 875 +/- 388 pg/ml, p less than 0.02). Plasma thromboxane B2 levels were in the normal range (mean 175 +/- 35 pg/ml) in patients with stable angina but significantly (p less than 0.02) higher in patients with spontaneous angina. With atrial pacing to the point of chest pain and/or ECG changes in patients with stable coronary artery disease, aortic thromboxane B2 concentrations increased in 10 of 13 patients (mean 283 +/- 70 pg/ml, p less than 0.02). Coronary venous thromboxane B2 concentrations increased in seven patients at peak pacing rates (mean 223 +/- 76 pg/ml) and in three other patients after termination of pacing. These data indicate that release of thromboxane A2 is much greater during spontaneous angina than with pacing stress in patients with coronary artery disease. Thromboxane A2 released during spontaneous or pacing-induced angina may modulate coronary and systemic vascular tone. Enhanced thromboxane A2 activity may either precede or follow myocardial ischemia and could be a factor in the initiation and propagation of the ischemic episode.     

Exercise induces in vivo platelet activation in patients with coronary artery disease and in healthy individuals

Recently, conflicting results have been published about a possible relationship between platelet activity and exercise-induced myocardial ischemia. The present study was performed to investigate platelet behavior during a graded symptom-limited bicycle ergometer test both in relation to the intensity of exercise and to exercise-induced myocardial ischemia. Plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured by radioimmunoassays in 53 patients who had had acute myocardial infarction 10 weeks before the study and, for comparison, in 9 healthy individuals. In the whole group of the 53 patients there was no significant alteration in platelet-specific proteins during exercise, whereas physical activity induced a 2- to 3-fold increase in beta-TG and PF4 levels in the controls. However, on differentiation of the patients as to their individual exercise performance, significant exercise-associated platelet activation was demonstrable in those who reached more than 75% of their calculated maximal working capacity, whereas no correlation was found between platelet activity and exercise-induced myocardial ischemia. Thus, the results from this study indicate that in vivo platelet activation is a physiological phenomenon which occurs when a certain degree of physical intensity is exceeded, independent of the precipitation of myocardial ischemia.     

Functional importance of coronary collateral vessels

Angiographically demonstrable coronary collateral vessels are believed to preserve myocardial function at rest, but disagreement exists regarding the importance of collaterals in mitigating exercise-induced ischemic dysfunction. Therefore, we used radionuclide cineangiography during exercise to assess the left ventricular (LV) functional effects of collateral vessels in 125 patients with at least 1 major coronary artery that had greater than or equal to 90% diameter stenosis but without prior myocardial infarction. Regional LV function, graded on a 4-point scale, worsened during exercise by at least 1 grade in 14 of 43 regions (33%) with good collaterals, and in 70 of 98 without good collaterals (p less than 0.001). Of the 43 good collaterals, 14 were supplied by arteries with greater than or equal to 75% stenoses; 10 of 14 regions (71%) thus supplied worsened by at least 1 grade (p less than 0.01). The ischemia-mitigating effect of coronary collateral vessels also affected the magnitude of exercise-induced global dysfunction. Of 43 patients with only one greater than or equal to 90% stenotic artery, 18 had good collaterals; in these patients, average LV ejection fraction (EF) at rest was 51 +/- 8%; LVEF during exercise was 46 +/- 7%. In the 25 patients without good collaterals, LVEF at rest was 52 +/- 7%, and LVEF during exercise was 41 +/- 9% (p less than 0.005 vs good collaterals).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrinopeptide A and beta thromboglobulin in patients with angina pectoris and acute myocardial infarction

The purpose of this study was to investigate the degree of platelet activation and thrombin generation in 40 patients with stable angina pectoris and in 20 patients with acute myocardial infarction (AMI) by determining the plasma beta thromboglobulin (BTG) and fibrinopeptide A (FPA) concentrations. In patients with angina pectoris increased platelet activation correlated with extensive coronary pathology; the activation, however, was not influenced by a previous myocardial infarction, use of oral anticoagulants, beta-blocking agents, or hyperlipidemia. The plasma beta thromboglobulin concentration predicted more accurately the extent of the coronary artery disease than the functional angina pectoris classification. Thrombin generation was within the normal range. In patients with acute myocardial infarction increased platelet activation and enhanced thrombin generation were found, which were not related to the infarct localization, infarct size, or the presence of complications. Consequently, in these patients determination of plasma beta thromboglobulin and fibrinopeptide A concentrations is useless for the diagnosis of venous thromboembolism.     

In vivo effects of nonionic and ionic contrast media on beta-thromboglobulin and fibrinopeptide levels.

Nonionic contrast media are suggested to cause increased thromboembolism (in vivo), platelet aggregation and procoagulant effect (in vitro) as compared with ionic contrast media. To study these effects in vivo, 30 consecutive patients undergoing routine angiography were prospectively randomized to three groups of 10 patients each. Group A received diatrizoate (ionic, high osmolality), Group B ioxaglate (ionic, low osmolality) and Group C iohexol (nonionic, low osmolality). In vivo platelet alpha-granule release and fibrin-1 formation were measured by radioimmunoassay of beta-thromboglobulin and fibrinopeptide A in peripheral venous samples. Levels were estimated at three stages during the procedure: before and after left ventriculography and after coronary angiography. No differences were noted (p = NS) when the ratios of beta-thromboglobulin and fibrinopeptide A were compared among the three groups. These data suggest that the newer nonionic contrast media do not demonstrate enhanced systemic platelet activation or fibrin formation as compared with standard ionic contrast media. However, larger randomized clinical studies are necessary to conclusively establish the suggested thromboembolic potential of nonionic contrast media.     

Fibrinopeptide A is released into the coronary circulation after coronary spasm

To examine whether acute myocardial ischemia activates the coagulation system and platelet activation in the coronary circulation, we measured plasma levels of fibrinopeptide A and beta-thromboglobulin in the coronary sinus and the aortic root simultaneously in 15 patients with coronary spastic angina before and after the left coronary spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Fifteen patients with chest pain but normal coronary arteries and no coronary spasm served as controls. The coronary sinus-arterial difference of fibrinopeptide A increased markedly (p less than 0.001) from 0.1 +/- 0.2 to 4.3 +/- 0.7 ng/ml after the anginal attacks in the coronary spastic angina group. However, fibrinopeptide A levels remained unchanged after the attacks in the stable exertional angina group and after intracoronary injection of acetylcholine in the control group. Plasma beta-thromboglobulin levels remained unchanged after the attacks in both patient groups and after acetylcholine in the control group. Our data indicate that coronary spasm induces thrombin generation and may lead to thrombus formation in the coronary artery involved, but pacing-induced ischemia does not activate the coagulation system.     

Myocardial infarct of effort with normal coronaries. Study of in vivo platelet activation

Platelet activation may play a part in causing myocardium infarction with angiographically normal coronary arteries. We investigated this possibility by performing ergometric stress testing in a series of 9 patients (Group A) who had suffered myocardial infarction after a violent effort with angiographically documented coronary insufficiency responsible for a stable effort angina (Group B) and 11 healthy subjects (Group C). Blood samples were taken separately before exercise, at the peak of exercise, and during the recovery period. Platelet morphology, a sensitive indication of the degree of platelet activation, was studied by phase contrast microscopy after immediate fixation of the blood. The percentage of non-discoidal platelets presenting with one or several spicules was measured. At the same time, the plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured. At rest, there was no difference in platelet morphology or specific platelet proteins between the 3 groups. At the peak effort, there was a significant increase of the number of morphologically modified platelets in Groups A and B but not in healthy subjects. This platelet activation could not be linked to the presence of myocardial ischaemia because it was found both in patients with a negative maximal exercise stress test (Group A). Finally, no increase of the plasma concentrations of the platelet protein was observed in any of the groups.     

Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia

Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.     

Platelet factor 4 release during exercise in patients with coronary artery disease

Many recent studies provide evidence that increased platelet activation occurs in a significant number of patients with atherosclerotic coronary artery disease. The mechanisms responsible for this activation are unknown, although there have been studies suggesting a correlation with abnormal lipoproteinemia, acute myocardial infarction, unstable angina, and exercise-induced myocardial ischemia. We studied 84 patients undergoing standardized treadmill exercise using either a Bruce [N = 63] or symptom-limited Naughton protocol [N = 21]. In contrast to ten healthy volunteer subjects, the patient group demonstrated a significant increase in plasma concentrations of platelet factor 4 [PF4] between pre- and postexercise blood samples confirming earlier reports of exercise-induced platelet activation and secretion. As with previous studies, however, only a subset of patients demonstrated this response. When the entire group was analyzed for the presence or absence of electrocardiographic ischemic changes and the presence of documented versus suspected coronary artery occlusions, there were no differences noted between groups that explained the variable responses measured. However, there was a significant difference between patient groups when analyzed by whether or not they were being treated with β-blocking agents. Patients who were being treated with propranolol or one of the longer-acting β-blocking agents did not have a significant increase in plasma PF4 following exercise, in contrast to patients who were not β-blocked. Plasma concentrations of epinephrine, norepinephrine, and lactic acid were measured in 49 patients and all normal subjects. There was no correlation between the changes in plasma PF4 concentrations and any of these three variables, suggesting that platelet activation was not occurring through direct platelet activation by circulating catecholamines. This study provides further evidence that there is a subset of CAD patients with platelet hyperactivity. This is the first time that β-blockade has been demonstrated to modify this platelet response. The effectiveness of β-blocking agents in CAD may be in part related to their antiplatelet effect.     

Comparison of platelet function during exercise in normal subjects and coronary artery disease patients: Potential role of platelet activation in myocardial ischemia

Platelet function parameters as influenced by exercise stress were evaluated in 22 patients with coronary artery disease (CAD) and in 13 normal subjects. Upon exercise stress, 14 CAD patients exhibited positive tests and eight exhibited negative tests. Platelet counts during exercise increased similarly in normal and CAD patients. Platelet aggregation response to ADP was unaffected by exercise both in normal and CAD patients. Platelets from 7 of the 14 CAD patients with positive stress tests had increased sensitivity to endoperoxide analog (U-46619) defined as less than 200 ng/ml U-46619 required for 50% platelet aggregation. Resting plasma beta-thromboglobulin (B-TG) levels, an index of in vivo platelet activation, were significantly higher in CAD patients compared to normal subjects (74 +/- 7 and 41 +/- 5 ng/ml, respectively; p less than 0.02). During exercise plasma B-TG levels increased in normal subjects to 60 +/- 5 ng/ml. In contrast, B-TG levels increased to 102 +/- 14 ng/ml in CAD patients (p less than 0.01 compared to normal subjects). These increases were transient and B-TG declined to preexercise values soon after exercise. Eleven of the 12 CAD patients with positive exercise stress tests had increases in plasma B-TG levels, whereas only three of the eight CAD patients with negative stress tests had any increase. These observations of increased platelet activation in certain CAD patients during exercise may be related to exercise-induced myocardial ischemia.     

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 (beta TG). Studies that attempt to correlate increases in PF4 and beta TG levels with exercise-induced myocardial ischemia have yielded conflicting results. To further examine the natural history of release of PF4 and beta TG 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 beta TG 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 beta TG. 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.     

Idiopathic hypertrophic subaortic stenosis: evaluation of anginal symptoms with thallium-201 myocardial imaging.

The evaluation of angina pectoris in patients with idiopathic hypertrophic subaortic stenosis is difficult in those in the age group prone to coronary artery disease. Ten patients with angina pectoris, normal coronary angiograms and idiopathic hypertrophic subaortic stenosis were studied with thallium-201 myocardial imaging performed in conjunction with submaximal treadmill exercise testing. The resting electrocardiogram demonstrated left ventricular hypertrophy with S-T segment abnormalities in seven patients, thereby vitiating the further increase in S-T segment abnormalities that developed in these patients during exercise or in the postexercise period. Of the three patients with a normal resting electrocardiogram, one had significant exercise-induced S-T segment depression. Thallium-201 myocardial imaging revealed no significant perfusion defects in 9 of the 10 patients (90 percent). In one patient with severe left ventricular hypertrophy significant perfusion defects developed after exercise that were not present at rest. Stress thallium-201 myocardial perfusion imaging is a useful noninvasive technique that assists in ruling out the presence of significant coronary artery disease in patients with idiopathic hypertrophic subaortic stenosis.     

Noninvasive myocardial imaging with potassium-43 and rubidium-81 in patients with left bundle branch block

Noninvasive myocardial imaging with potassium-43 and rubidium-81 has been used successfully to identify areas of infarction and exercise-induced ischemia as regions of decreased radioactivity. The image defects observed are believed to be due to a decreased radionuclide uptake in regions of myocardial scar or to heterogeneous myocardial accumulation of tracer as a result of regional ischemia. Of 27 patients with left bundle branch block studied with noninvasive imaging at rest and during exercise, 25 manifested at rest reduced radioactivity in the region of the interventricular septum. This pattern is similar to that seen in patients with anteroseptal myocardial infarction. Sixteen of the 27 patients underwent diagnostic coronary arteriography and left ventriculography. Only five of these patients had evidence of either previous infarction or significant obstructive coronary artery disease as assessed with clinical or anglographic criteria, or both. Although the image defect was routinely demonstrated at rest in patients with left bundle branch block, this defect was generally normalized or less distinct with exercise in patients with no anatomic heart disease. In contrast, a larger, more distinct or new image defect with exercise correctly identified the presence of significant obstructive coronary artery disease in patients with left bundle branch block. In the clinical application of noninvasive myocardial imaging, these image defects observed at rest can lead to the false positive radionuclide interpretation of anteroseptal myocardial infarction.     

Influence of exercise-induced myocardial ischemia on the pattern of left ventricular diastolic filling: a Doppler echocardiographic study

Previous studies using Doppler echocardiography to evaluate left ventricular diastolic filling have shown that myocardial ischemia induced by coronary balloon angioplasty or atrial pacing results in a decrease in the left ventricular inflow peak early (E) to peak atrial (A) velocity ratio. To investigate the effects of exercise-induced ischemia on Doppler-derived filling variables, 20 patients with coronary artery disease and exercise-induced electrocardiographic changes and regional wall motion abnormalities determined by two-dimensional echocardiography were evaluated and compared with 20 patients without evidence of exercise-induced ischemia. Doppler echocardiography was performed at rest and immediately after exercise before the resolution of exercise-induced wall motion abnormalities. Peak E and A velocities increased from rest to postexercise in both the ischemic and nonischemic groups, although the ischemic group demonstrated a greater increase in peak E velocity (from 68 +/- 15 cm/s at rest to 88 +/- 22 cm/s after exercise) than the nonischemic group (70 +/- 13 to 77 +/- 18 cm/s) (p less than 0.05 for the difference in response between groups). Accompanying these changes was a slight increase in the peak E/A velocity ratio in the ischemic group (1.04 +/- 0.28 at rest to 1.13 +/- 0.42 after exercise) versus a decrease in the nonischemic group (1.07 +/- 0.30 to 0.90 +/- 0.28) (p less than 0.05 intergroup difference).(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of inducible painless myocardial ischemia by conventional medical therapy: Effect on short-term outcome and left ventricular systolic function

To test the hypothesis that abolition of exercise-induced painless myocardial ischemia by antiischemic medication improves prognosis in patients with medically treated coronary artery disease, we studied such patients with painless ischemia during exercise radionuclide ventriculography performed after temporary discontinuation of medication. The test was repeated while patients received conventional medical therapy that rendered angina no worse than New York Heart Association class I. The relative risk of adverse cardiac events was reduced by >5-fold when painless ischemia was abolished by symptom-dictated therapy. Thus, the abolition of exercise-induced painless ischemia by conventional medical therapy carries a better short-term prognosis in medically treated coronary artery disease, suggesting that therapeutic efficacy may need to be assessed by titration against ischemia and not angina. In patients without overt cardiac events, there were no significant differences between baseline and 12-month measurements of ejection fraction at rest, peak exercise, and the change in ejection fraction from rest to exercise. Thus, in those who remain asymptomatic and event-free, painless ischemia that is easily inducible at baseline despite medication does not lead per se to deterioration of left ventricular systolic function at rest or during exercise over 12 months. Such an effect, if evident as early as at 12 months, would favor a strategy of early revascularization over medical treatment in asymptomatic patients who have inducible painless ischemia despite medication.