The effects of intracoronary adenosine on preconditioning during coronary angioplasty

There is evidence that the first balloon inflation during coronary angioplasty provides a preconditioning stimulus leading to decreased ischemia during subsequent balloon inflations. Endogenous adenosine release may play a role in ischemic preconditioning. Therefore, intracoronary adenosine administration prior to the first balloon inflation during percutaneous transluminal coronary angioplasty (PTCA) might modify the preconditioning response to the first balloon inflation. Forty-one patients underwent double-blind randomization to treatment with 100 mcg of intracoronary adenosine or placebo prior to coronary angioplasty. Twenty patients (11 adenosine, 9 placebo) had complete resolution of ischemia between inflations allowing comparison between the first and second inflation. An angioplasty guidewire was used to obtain an intracoronary electrocardiogram. The mean reduction in ST elevation during the second inflation compared with the first was 4.8 mm in the placebo group and -0.8 in the adenosine group (p<0.05 placebo vs. adenosine). Seven of 9 placebo patients had a decrease in ischemia during the second inflation compared with the first, while only 2 of 11 adenosine patients showed a reduction. It was concluded that (1) the first inflation during PTCA is a preconditioning stimulus leading to a decrease in ischemia during later inflations, and (2) intracoronary adenosine administration prior to PTCA modifies the preconditioning effect of the first inflation. These data suggest that adenosine plays a role in ischemic preconditioning in humans.     

Mechanism of exercise-induced ST depression based on hemodynamics during cardiac catheterization

OBJECTIVES: The cause of exercise-induced ST depression was studied by assessing left ventricular end-diastolic pressure (LVEDP). METHODS: This study included 28 patients with normal coronary artery, 24 patients with vasospastic angina pectoris and 28 patients with fixed organic lesion who underwent both treadmill exercise testing and selective coronary arteriography. Exercise-induced ST deviation was considered as maximal ST deviation during the exercise test and maximum LVEDP was considered as the pressure measured 1 min after left ventriculography. RESULTS: The degree of exercise-induced ST depression in aVF showed no significant differences between the three groups. Exercise-induced ST elevation occurred in the intracardiac leads and exercise-induced ST depression occurred in the epicardial leads. These electrocardiographic changes were not contradictory to subendocardial ischemia. In addition, there was a good correlation (r = - 0.465, p < 0.01) between exercise-induced ST depression and maximum LVEDP elevation. CONCLUSIONS: Exercise-induced ST depression was caused by subendocardial ischemia due to increased LVEDP.     

Surface electrocardiogram in the detection of transmural myocardial ischemia during coronary artery occlusion

To examine whether coronary occlusion causing transmural ischemia was accurately reflected by ST-segment elevation on routine electrocardiograms, intracoronary and surface electrocardiograms were simultaneously recorded during percutaneous transluminal coronary angioplasty (PTCA). The study group consisted of 54 patients who had intracoronary ST-segment elevation during transient coronary occlusion (left anterior descending [LAD]: 25 patients, left circumflex [LC]: 19 patients, right coronary artery: 12 patients). Elevation of the ST segment on the surface electrocardiogram (greater than or equal to 0.1 mV) was recorded in 84% of patients during LAD dilatation, in 32% of patients during LC dilatation (p less than 0.01 vs LAD and right), and in 92% of patients during right coronary dilatation (not significant vs LAD). The magnitude of intracoronary ST elevation was 1.10 +/- 0.8, 1.68 +/- 1.2 and 0.8 +/- 0.6 mV for the LAD, LC and right occlusions, respectively (not significant). Thus, despite the comparable magnitude of intracoronary ST elevation, LC occlusion resulted in ST-segment elevation on the surface electrocardiogram in significantly fewer patients than did LAD or right occlusion. During LC occlusion, 9 patients had no electrocardiographic changes and 4 had only precordial ST depression. Thus, in patients with transmural ischemia during right or LAD occlusions, concordant ST elevation on the surface electrocardiogram is common. In contrast, ST-segment elevation is an insensitive marker of LC occlusion. In patients with ongoing ischemic symptoms and isolated precordial ST depression or no repolarization abnormalities, LC occlusion should be considered in the differential diagnosis.     

Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?

OBJECTIVES: The purpose of this study in patients with quantitatively determined, poorly developed coronary collaterals was to assess the contribution of ischemic as well as adenosine-induced preconditioning and of collateral recruitment to the development of tolerance against repetitive myocardial ischemia. BACKGROUND: The development of myocardial tolerance to repeated ischemia is nowadays interpreted to be due to biochemical adaptation (i.e., ischemic preconditioning). METHODS: In 30 patients undergoing percutaneous transluminal coronary angioplasty, myocardial adaptation to ischemia was measured using intracoronary (i.c.) electrocardiographic (ECG) ST segment elevation changes obtained from a 0.014-in. (0.036 cm) pressure guidewire positioned distal to the stenosis during three subsequent 2-min balloon occlusions. Simultaneously, an i.c. pressure-derived collateral flow index (CFI, no unit) was determined as the ratio between distal occlusive minus central venous pressure divided by the mean aortic minus central venous pressure. The study patients were divided into two groups according to the pretreatment with i.c. adenosine (2.4 mg/min for 10 min starting 20 min before the first occlusion, n = 15) or with normal saline (control group, n = 15). RESULTS: Collateral flow index at the first occlusion was not different between the groups (0.15 +/- 0.10 in the adenosine group and 0.13 +/- 0.11 in the control group, p = NS), and it increased significantly and similarly to 0.20 +/- 0.14 and to 0.19 +/- 0.10, respectively (p < 0.01) during the third occlusion. The i.c. ECG ST elevation (normalized for the QRS amplitude) was not different between the two groups at the first occlusion (0.25 +/- 0.13 in the adenosine group, 0.25 +/- 0.19 in the control group). It decreased significantly during subsequent coronary occlusions to 0.20 +/- 0.15 and to 0.17 +/- 0.13, respectively. There was a correlation between the change in CFI (first to third occlusion; deltaCFI) and the respective ST elevation shift (deltaST): deltaST = -0.02 to 0.78 x deltaCFI; r = 0.54, p = 0.02. CONCLUSIONS: Even in patients with few coronary collaterals, the myocardial adaptation to repetitive ischemia is closely related to collateral recruitment. Pharmacologic preconditioning using a treatment with i.c. adenosine before angioplasty does not occur. The variable responses of ECG signs of ischemic adaptation to collateral channel opening suggest that ischemic preconditioning is a relevant factor in the development of ischemic tolerance.     

"Warm-up" phenomenon in adult and elderly patients with coronary artery disease: further evidence of the loss of "ischemic preconditioning" in the aging heart

BACKGROUND: A reduction of exercise-induced ischemia in patients with coronary artery disease by means of brief period of exercise followed by resting is called the "warm-up" phenomenon. This phenomenon may represent a clinical counterpart of "ischemic preconditioning." We studied the warm-up phenomenon in both adult and elderly patients with similar angiographic evidence of coronary artery disease, using three exercise tests after excluding the "training effect." METHODS: In order to verify the presence of "training effect," three exercise tests were performed in days 1, 2, and 3 ("training" tests). The third test was used as baseline for a successive test, performed after a recovery period of 10 minutes to reestablish baseline electrocardiographic conditions. A third exercise test was performed 30 minutes later ("warm-up" tests). RESULTS: "Training" tests did not differ in all parameters in both adult and elderly patients. "Warm-up" tests showed that time to onset 1-mm ST depression was significantly higher (p < .001). whereas ST depression and time to recovery was significantly lower in the second and third test in adult but not in elderly patients (p < .001 ). Difference (in seconds) in the time at which 1-mm ST depression occurred on first warm-up exercise compared with the second was inversely correlated with age (p < .001 ). CONCLUSIONS: Previous exercise followed by resting is able to reduce the successive exercise-induced ischemia ("warm-up" phenomenon) in adult but not in elderly patients with coronary artery disease. This is independent of a greater age-related severity of coronary disease and of "training effect." These results confirm the hypothetical age-related reduction of "ischemic preconditioning" in aging heart.     

Intracoronary administration of dipyridamole prior to percutaneous transluminal coronary angioplasty provides a protective effect exceeding that of ischemic preconditioning

BACKGROUND: Ischemic preconditioning renders hearts more resistant to the deleterious consequences of ischemia. Adenosine is an important mediator in the induction and maintenance of ischemic preconditioning. Percutaneous transluminal coronary angioplasty (PTCA) allows the investigation of the consequences of ischemia in humans. The severity of myocardial ischemia decreases with subsequent balloon inflations during the course of PTCA. OBJECTIVE: To compare the effect of intracoronary administration of dipyridamole with the effect of consecutive balloon inflations. METHODS: We investigated 30 patients undergoing PTCA of the left anterior descending coronary artery in the setting of stable angina pectoris. Patients were randomly allocated to be administered either 0.5 mg/kg body weight dipyridamole intracoronarily or an equal amount of saline. Patients administered saline served as a control group. All patients were subjected to three consecutive balloon inflations. Severity of myocardial ischemia was assessed in terms of severity of chest pain, electrocardiographic signs of ischemia, and duration of balloon inflation tolerated. RESULTS: Patients administered dipyridamole intracoronarily tolerated significantly longer durations of balloon inflation than did patients in the control group. Severity of anginal pain and extent of electrocardiographic signs of ischemia were significantly lower after intracoronary administration of dipyridamole. The reductions in anginal pain and ST-segment shift caused by intracoronary administration of dipyridamole during the first balloon inflation were even more pronounced than the protection that was afforded by the third balloon inflation for patients in the control group. CONCLUSIONS: Intracoronary administration of dipyridamole prior to PTCA is associated with a significant gain in tolerance of ischemia. The protection afforded by intracoronary administration of dipyridamole is even more pronounced than the effect of ischemic preconditioning.     

Significance of exercise-induced ST changes in leads aVR,V5, and V1. Discrimination of patients with single- or multivessel coronary artery disease

BACKGROUND: It is known that exercise-induced ST-segment elevation in lead V1 (V1-E) detects left anterior descending (LAD) stenosis. It was also postulated that ST elevation in aVR and simultaneous ST depression in V5 (aVR-E + V5-D) is a marker of ischemia due to significant stenosis of the LAD in patients with single-vessel disease. HYPOTHESIS: This study was undertaken to investigate the significance of the concomitant appearance of both electrocardiographic (ECG) ischemic markers, and of each of them alone during exercise, to detect either LAD stenosis as single-vessel coronary artery disease (CAD), or multivessel CAD involving LAD stenosis. METHODS: A total of 196 consecutive patients (152 men and 44 women, mean age 54 +/- 7 years) with at least one of these ECG markers, who underwent treadmill exercise testing with the Bruce protocol and coronary arteriography, were studied. RESULTS: Patients were divided into three groups. In Group A (83 patients with V1-E + aVR-E & V5-D), 93% of patients with single-vessel disease had significant LAD stenosis (p<0.001), whereas 75% of patients with double-vessel disease had significant stenoses of the LAD and the left circumflex (LCx) coronary arteries (p<0.01). In Group B (97 patients with aVR-E & V5-D but without V1-E), 43% of patients with single-vessel disease had significant LAD stenosis (p<0.08), whereas 85% of patients with double-vessel disease had significant stenoses of the LAD and the right coronary artery (RCA) (p<0.01). In Group C (16 patients with only V1-E), 60% of patients with single-vessel disease had significant LAD stenosis (p<0.05), whereas 75% of patients with double-vessel disease had significant LAD and LCx stenoses (p<0.05). CONCLUSIONS: The concomitant appearance of exercise-induced ST elevation in lead V1, ST elevation in lead aVR, and ST depression in lead V5, as well as the isolated appearance of ST elevation in lead V1 detect significant LAD stenosis as single-vessel disease, or significant stenoses of LAD and LCx arteries in patients with double-vessel disease, whereas the appearance of ST elevation in aVR & ST depression in V5 but without ST elevation in V1 correlates strongly with significant LAD and RCA stenoses and usually indicates double-vessel disease.     

经皮冠状动脉腔内成形术缺血预适应对QT离散度的影响

记录７０例冠心病人经皮冠状动脉腔内成形术时体表和冠脉内心电图发现，随球囊充盈次数增加，ＳＴ段抬高幅度减低，心绞痛出现时间延长，最大ＱＴ间期缩短及ＱＴ离散度和ＪＴ离散度减低，提示ＰＴＣＡ时多次短暂心肌缺血可能由于缺血预适应而诱发心肌内在抗心律失常保护作用。     

活动平板运动试验诱发ST段抬高的临床意义

为探讨活动平板运动试验诱发ST段抬高的临床意义 ,分析了 9例无心肌梗死 (简称心梗 )而运动诱发ST段抬高的静息心电图、运动试验及冠状动脉 (简称冠脉 )造影检查结果。结果 :5 0 5 5例行平板运动试验者中 ,有 11例未患心肌梗死而运动诱发心绞痛伴ST段抬高 ,发生率 0 .2 2 %。其中 ,8例患者作了进一步检查 ,冠脉造影显示均有程度不等的血管病变 ,缺血相关血管的狭窄达到 5 0 %～ 10 0 %。ST段抬高导联与缺血相关血管有良好对应关系。另有 1例患者于运动试验 1周后死于心脏性猝死。结论 :无心梗患者运动诱发心电图ST段抬高是冠脉痉挛或冠脉严重狭窄所致心肌局部缺血的标志。     

Beneficial effects of intracoronary nifedipine during percutaneous transluminal coronary angioplasty

In twelve patients with coronary heart disease and hemodynamically significant coronary artery stenoses (LAD: 11, LAD plus RCA: 1) the effect of intracoronary nifedipine, 0.2 mg, on PTCA-related myocardial ischemia was evaluated. The severity of angina pectoris during balloon inflation was not significantly reduced by nifedipine, whereas the sum of ST segment alterations in Einthoven and Goldberger leads on inflation was significantly decreased by the drug. Before inflation intracoronary nifedipine lowered the systolic arterial blood pressure significantly, whereas diastolic and mean aortic pressure and heart rate remained unchanged. At the end of the inflation period heart rates were significantly faster after nifedipine, and the heart rate-blood pressure product higher with nifedipine. No significant correlations could be calculated between the extent of ST segment alterations and any of the hemodynamic parameters. From our results we conclude that, besides the possibility of ventricular afterload reduction, the beneficial cardioprotective effect of intracoronary nifedipine may mainly be attained by the local "cardioplegic" action of this substance.     

ECG Diagnosis of Coronary Artery Disease

Objective: In order to assess the diagnostic accuracy of ST depression in the diagnosis of coronary artery disease (CAD) in patients with suspected myocardial ischemia we compared ST depression in 3-lead ambulatory ECG (AECG) with that of exercise tolerance testing (ETT). Methods: Significant coronary artery stenosis in coronary angiography was used as a standard reference. ST analysis could be performed in 106 of the investigated 113 patients, all with suspected CAD. One person with left bundle branch block was excluded from the ST analysis, and six persons could not perform ETT. Results: Seventy-eight of the 106 patients had at least one significant stenosis (> 70% narrowing) and 28 had no stenosis according to coronary angiography. The sensitivity for AECG was 62% and for ETT it was 63%, the specificity for AECG was 79% and for ETT the specificity was 57%. The accuracy for AECG was 66%, and for ETT it was 61%. We also evaluated late potentials (LPs) from the AECG tapes in order to correlate LP to left ventricular function (LVF), myocardial infarction (Ml), and/or CAD. We found that LP correlates better to advanced CAD than to Ml or LVF. Conclusion: The accuracy of ST diagnosis of CAD in patients with suspected myocardial ischemia using AECG was equal to that of a maximal ETT. LP finding from an AECG tape may support the argument for CAD in patients with ST depressions at AECG.     

Low-dose dipyridamole infusion acutely increases exercise capacity in angina pectoris: a double-blind, placebo controlled crossover stress echocardiographic study

OBJECTIVES: The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND: Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS: Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS: In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs. dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS: Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity A1 myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals.     

Hypercholesterolemia attenuates the anti-ischemic effect of preconditioning during coronary angioplasty

BACKGROUND: Cardioprotection by preconditioning is limited in some animal models of hypercholesterolemia. We studied ischemic preconditioning induced by coronary angioplasty in hypercholesterolemic and normocholesterolemic patients by means of a beat-to-beat analysis of ST segments. METHODS: Thirty coronary disease patients were classified into normocholesterolemic and hypercholesterolemic groups. Intracoronary ECG was recorded during three consecutive balloon inflations of 2-min duration with 5-min intervals. RESULTS: In normocholesterolemic patients, the ST segment was continuously elevated during the occlusions and rapidly normalized after balloon deflations. Repeated occlusions significantly attenuated ST-segment elevation from 1.28 +/- 0.67 to 0.88 +/- 0.51 mV (p < 0.001) and decreased the time to normalization of ST segment. In hypercholesterolemic patients, the ST segment was rapidly elevated in the first 30 s of the first occlusion, and normalization of the ST segment was longer on the first reperfusion. However, in these patients, repeated occlusions abolished the initial elevation of the ST segment but did not attenuate maximal ST-segment elevation (1.24 +/- 1.11 mV vs 1.21 +/- 1.09 mV) and failed to decrease the time to normalization of the ST segment. CONCLUSIONS: Hypercholesterolemia accelerates the evolution of myocardial ischemia, delays recovery on reperfusion, and deteriorates the anti-ischemic effect of preconditioning in humans.     

ATP-sensitive potassium channels do not have a main role in mediating late preconditioning protection against arrhythmias and stunning in conscious sheep

Objective Although late preconditioning protects against stunning following several short periods of ischemia-reperfusion, it is not clear if it confers protection against stunning and malignant arrhythmias after a sustained reversible ischemia, and whether KATP channels are involved as triggers and/or end effectors of the protective mechanism. The purpose of this work was thus to test these issues in conscious sheep. Methods Five groups were considered: CONT (control): the animals were submitted to 12 min ischemia followed by 2 h reperfusion; SWOP (late preconditioning): on the first day, the animals were preconditioned with 6 periods of 5 min ischemia 5 min reperfusion and 24 h later they were submitted to 12 min ischemia followed by 2 h reperfusion; GLIB: same as CONT with the KATP channel inhibitor glibenclamide (0.4 mg/kg) infused 30 min prior to the 12 min ischemia; SWOPG2: same as SWOP with glibenclamide before the 12 min ischemia; SWOPG1: same as SWOP with glibenclamide prior to the preconditioning stimulus. Results Percent reperfusion recovery of wall thickening fraction (% WTh) showed late preconditioning protection against stunning throughout reperfusion (SWOP vs CONT, p < 0.01). Arrhythmia severity index (ASI) also demonstrated that late preconditioning protects against malignant arrhythmias at the onset of reperfusion (CONT: 4.87 ± 1.62 vs SWOP: 1.39 ± 0.93, p < 0.01). Glibenclamide was unable to prevent preconditioning, both against stunning and arrhythmia incidence, when administered either before the preconditioning stimulus (SWOPG1 vs CONT, p < 0.01) or before the sustained ischemia (SWOPG2 vs GLI, p < 0.01). Conclusions Results indicate that late preconditioning protects against stunning and arrhythmias following a reversible, sustained ischemia in conscious sheep and that KATP channel participation is negligible as triggers and end effectors of both types of protection. Received: 19 March 2001, Returned for revision: 9 April 2001, Revision received: 14 May 2001, Accepted: 16 May 2001     

Determinants of exercise-induced ST-segment displacement in the aVL lead in patients with known or suspected coronary artery disease

Although the aVL lead in exercise electrocardiography is reported to be helpful in identifying a significant narrowing of the left anterior descending coronary artery (LAD), its role in exercise testing has not been fully evaluated. Accordingly, 821 patients who underwent both standard exercise testing and coronary angiography were evaluated. In patients with aVL lead ST elevation, the incidence of a significant narrowing of the LAD (124/165 vs 348/656; p<0.001) was higher than in those without. Multiple logistic regression analysis revealed that the 2 most important variables that correlated with aVL lead ST elevation were a greater number of leads with ST depression in the inferior leads and a smaller amplitude of R wave in the aVL lead. In contrast, variables correlating with aVL lead ST depression in the majority of cases were a greater number of leads with ST depression in all leads and the presence of inferior lead ST elevation. The results of this study indicate that although aVL lead ST elevation could be a marker for LAD narrowing, more important factors such as inferior lead ST-segment depression and the R-wave amplitude of the aVL lead should be taken into consideration. In contrast, ST depression in the aVL lead mostly represents exercise-induced myocardial ischemia of greater extent and severity.     

Association of myocardial ischemia and coronary angiographic lesions with increased left atrial dimension during exercise tolerance tests among patients without known coronary heart disease

The association between left atrial (LA) dilation and fundamental exercise parameters has not shared equal extensive investigation as its clinical correlate, interatrial block (IAB; P waves > or =110 ms). We prospectively identified 94 consecutive patients with LA dilation on 2-dimensional transthoracic echocardiography but without atrioventricular valvular disease, hypertension, or coronary artery disease who had undergone coronary angiography after exercise tolerance tests (ETTs) for assessment of new coronary artery disease. Duke prognostic treadmill (DPT) scores were calculated and exercise capacity was expressed as METs of workload achieved. We appraised the cohort for common co-morbidities, IAB on electrocardiography at rest, and exercise-induced P-wave increments (divided into 20-ms quintiles). IAB (67% vs 34%, p = 0.002) and increased LA dimension (48 +/- 6 vs 45 +/- 5 mm, p = 0.01) were associated in patients with >70% coronary artery diameter stenoses and were equally reflected by positive ETT results (79.5% vs 20%, p <0.001), decreased METs (11.43 + [-0.60 x LA size (millimeters)], r(2) = 0.04), and lower DPT scores (35.23 + [-0.70 x LA size (millimeters)], r(2) = 0.73). Incremental P-wave change was associated with lower METs and DPT scores but with positive ETT results and significant coronary artery stenoses (p for trend <0.001). LA dimension was largest in the highest quintile (>60 ms) of P-wave change (p for trend <0.001). In conclusion, increased LA dimension is significantly associated with myocardial ischemia during ETT and is reflected by lower METs and DPT scores and a higher incidence of coronary artery diameter stenoses >70% in patients matched by age-, gender-, and LA size without preexisting coronary artery disease.     

Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: comparison with intracoronary streptokinase

To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction.     

Exercise performance-based outcomes of medically treated patients with coronary artery disease and profound ST segment depression

OBJECTIVES

We sought to determine the relationship between exercise duration and cardiovascular outcomes in patients with profound (≥2 mm) ST segment depression during exercise treadmill testing (ETT).

BACKGROUND

Patients with stable symptoms but profound ST segment depression during ETT are often referred for a coronary intervention on the basis that presumed severe coronary artery disease (CAD) will lead to unfavorable cardiovascular outcomes, irrespective of symptomatic and functional status. We hypothesized that good exercise tolerance in such patients treated medically is associated with favorable long-term outcomes.

METHODS

We prospectively followed 203 consecutive patients (181 men; mean age 73 years) with known stable CAD and ≥2 mm ST segment depression who are performing ETT according to the Bruce protocol for an average of 41 months. The primary end point was occurrence of myocardial infarction (MI) or death.

RESULTS

Eight (20%) of 40 patients with an initial ETT exercise duration ≤6 min developed MI or died, as compared with five (6%) of 84 patients who exercised between 6 and 9 min and three (3.8%) of 79 patients who exercised ≥9 min (p = 0.01). Compared with patients who exercised ≤6 min, increased ETT duration was significantly associated with a reduced risk of MI/death (6 to 9 min: relative risk [RR] = 0.25, 95% confidence interval [CI] 0.08 to 0.76; >9 min: RR = 0.14, 95% CI 0.04 to 0.53). This protective effect persisted after adjustment for potentially confounding variables. We observed a 23% reduction in MI/death for each additional minute of exercise the patient was able to complete during the index ETT.

CONCLUSIONS

Optimal medical management in stable patients with CAD with profound exercise-induced ST segment depression but good ETT duration is an appropriate alternative to coronary revascularization and is associated with low rates of MI and death.     

The lay of the land

To evaluate the presence and clinical significance of electrical alternans during PTCA, intracoronary electrocardiography (ic-ECG) was performed in 65 consecutive lesions. ST-T alternans, defined as a beat-to-beat difference in the ST elevation ?1 mm, was present in five lesions (7.7%), all in the proximal left anterior descending (LAD) coronary artery. The phenomenon was seen only after 130 sec (mean 174 ± 57) of balloon inflation. Only two of the five showed ST-T alternans simultaneously on both surface and ic-ECG. One of five patients had premature ventricular contractions following ST-T alternans. Three of these five lesions required a second balloon inflation with duration of ? 300 sec; there was no ST-T alternans on the second inflation in any of these lesions. We conclude: (1) the detection of ST-T alternans during PTCA is enhanced by use of ic-ECG, (2) electrical alternans during PTCA was seen only in proximal LAD lesions, implicating a large amount of ischemic myocardium as a requisite for the phenomenon, (3) electrical alternans is not immediate, requiring a certain duration of balloon occlusion and hence ischemia to occur, and (4) the absence of ST-T alternans during second balloon inflations suggests ischemic preconditioning may abolish this phenomenon.     

Pattern of exercise-induced ST change is related to coronary flow reserve in patients with chest pain and normal coronary angiogram

OBJECTIVE: To evaluate the usefulness of exercise treadmill test in determining the true microvasculature-induced ischemia, we compared the pattern of ST depression with coronary flow reserve (CFR) using transthoracic Doppler echocardiography (TTE) in patients with chest pain and normal coronary angiogram. DESIGN: Fifty-nine subjects (M/F=21:38, mean age 55+/-9 years) with chest pain and normal coronary angiogram underwent maximal symptom-limited exercise treadmill test (ETT). CFR was estimated with TTE and dipyridamole. Patients with a history of acute myocardial infarction, regional wall motion abnormalities, hypertrophic cardiomyopathy, ejection fraction less than 50%, or primary valvular heart disease were excluded from this study. RESULTS: No ST change was observed in 20 of 59 (34%) patients, up slope depression was observed in 20 (34%), flat depression in 13 (22%), and down slope depression in 6 (10%). Eleven of thirty nine (28%) exercise positive patients had decreased CFR <2.1. CFR was 3.1+/-0.6 in group with no ST change, 3.1+/-0.6 in group with up slope depression, 2.1+/-0.6 in group with flat depression (p<0.05 versus group with no change and group with upslope depression, respectively), and 2.0+/-0.4 in group with down slope depression (p<0.05 versus group with no change and group with up slope depression, respectively). Flat to down slope depression of ST change during ETT had sensitivity of 58% and specificity of 95% for predicting CFR <2.1. CONCLUSION: Flat and down slope depression of ST segment during ETT might increase the sensitivity and specificity to detect the true microvasculature-induced ischemia that is defined as CFR less than 2.1 in patients with chest pain and normal coronary angiogram.