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The impact of low-level carbon monoxide exposure on ventricular arrhythmia frequency in patients with ischemic heart disease has not been thoroughly studied. The issue is of concern because of the potential proarrhythmic effect of carbon monoxide in patients with ischemic heart disease. We studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. By using appropriate inclusion and exclusion criteria, subjects were selected and enrolled in a randomized double-blind study to determine the effects of carbon monoxide exposure on ventricular arrhythmia frequency at rest, during exercise, and during ambulatory activities. The carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. The carbon monoxide exposure protocol produced target levels in 60 minutes, and the levels were maintained for an additional 90 minutes to provide adequate time to assess the impact of carbon monoxide on the frequency of ventricular ectopic beats. The data on total and repetitive ventricular arrhythmias were analyzed for seven specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide or air exposure; (3) during a two-hour rest period; (4) during an exercise period; (5) during an exercise recovery period; (6) six hours after carbon monoxide or air exposure; and (7) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity. During steady-state conditions at rest, the number of ventricular ectopic beats per hour was 115 +/- 153 (SD) for room air exposure (0.7% carboxyhemoglobin), 121 +/- 171 for the lower carbon monoxide exposure (3.2% carboxyhemoglobin), and 94 +/- 129 for the higher carbon monoxide exposure (5.1% carboxyhemoglobin). The frequency of complex ventricular ectopy was not altered at the levels of carbon monoxide studied. Secondary analysis of the impact of carbon monoxide on ventricular ectopic beat frequency stratified by baseline ejection fraction, baseline ventricular ectopic beat frequency, and exercise-induced ST-segment changes did not indicate an effect of carbon monoxide on ventricular arrhythmias. In conclusion, low levels of carbon monoxide exposure resulting in blood levels of 3.2% and 5.1% carboxyhemoglobin, as measured by gas chromatography, do not have a proarrhythmic effect on patients with coronary artery disease and frequent ventricular ectopy.(ABSTRACT TRUNCATED AT 400 WORDS)

The ECG is the most widely used noninvasive diagnostic and prognostic test administered to patients with suspected or proven coronary artery disease. When considering appropriate use of the electrocardiogram, physicians need to examine the clinical question being asked, the additional information that can be derived, whether or not a diagnosis can be established, and application of the information to make appropriate management decisions.

Intravenous dipyridamole planar thallium-201 imaging is a safe and effective test for detection and prognosis of coronary artery disease (CAD) in the general population. The relative diagnostic accuracy and side-effect profile of dipyridamole thallium-201 stress imaging in women is not defined. Forty-three consecutive female and 71 male patients who underwent dipyridamole thallium-201 imaging (0.56 mg/kg) within 3 months of cardiac catheterization were studied. Scans were considered abnormal if fixed or reversible perfusion defects were detected. Stenosis severity of greater than or equal to 50% luminal diameter reduction of any artery defined CAD. Overall sensitivity for detection of CAD was 0.87 in women and 0.94 in men; specificity was 0.58 in women and 0.63 in men (p = not significant). Sensitivity for detection of 1-vessel CAD was 0.60 in women and 0.94 in men (p = 0.001). The sensitivity for detection of multivessel CAD (with or without surgical revascularization) was 1.0 and 0.94 in women and men, respectively. Adverse effects were reported in 62% of women and in 38% of men (p = 0.01). There was no significant difference in the incidences of chest pain, headache, nausea, flushing or electrocardiographic changes. The incidences of severe ischemia and dizziness were higher in women. Possible explanations for this difference in adverse effects include gender differences in the volume of distribution of dipyridamole due to varied fat-to-muscle ratios and different subjective nocioceptive sensitivities to the effects of dipyridamole. Overall sensitivity and specificity are comparable between the sexes.

Having previously shown in the Heparin Aspirin Reperfusion Trial that the empiric use of early intravenous heparin after recombinant tissue-type plasminogen activator (rt-PA) is an important component in the overall treatment strategy, we examine in this report the specific relation between the degree of prolongation of activated partial thromboplastin time and coronary artery patency. To evaluate the hypothesis that arterial patency after administration of rt-PA for acute myocardial infarction is sustained by effective anticoagulation, activated partial thromboplastin time of heparin recipients was determined 8 and 12 h after the start of thrombolysis. Mean activated partial thromboplastin time was higher among patients with an open infarct-related artery than in those with a closed artery (81 +/- 4 vs. 54 +/- 9 s, p less than 0.02). Only 45% of patients with values less than 45 s at both 8 and 12 h had Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 in the infarct-related artery at 18 h. In contrast, 88% of patients with activated partial thromboplastin time greater than 45 s and 95% of those with values greater than 60 s had an open infarct-related artery at 18 h (p = 0.003 and 0.0006, respectively). Among patients with an initially patent infarct-related artery who underwent repeat angiography at 7 days, activated partial thromboplastin time was similar in those with a persistently patent artery and those with late reocclusion. Excessive anticoagulation did not appear to increase hemorrhagic risk except that access site-related hemorrhage was more common in patients with activated partial thromboplastin time greater than 100 s at 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic value of intravenous dipyridamole myocardial perfusion imaging has not been studied in a large series of elderly patients. Patients greater than or equal to 70 years of age with known or suspected coronary artery disease were evaluated to determine the predictive value of intravenous dipyridamole thallium-201 imaging for subsequent cardiac death or nonfatal myocardial infarction. Of the 348 patients, 207 were symptomatic and 141 were asymptomatic; 52% of the asymptomatic group had documented coronary artery disease. During 23 +/- 15 months of follow-up, there were 52 cardiac deaths, 24 nonfatal myocardial infarctions and 42 revascularization procedures (percutaneous transluminal coronary angioplasty in 20; coronary artery bypass surgery in 22). Clinical univariate predictors of a cardiac event included previous myocardial infarction, congestive heart failure symptoms, hypercholesterolemia and diabetes (all p less than 0.05). The presence of a fixed, reversible or combined thallium-201 defect was significantly associated with the occurrence of cardiac death or myocardial infarction during follow-up (p less than 0.05). Cardiac death or nonfatal myocardial infarction occurred in only 7 (5%) of 150 patients with a normal dipyridamole thallium-201 study (p less than 0.001). Stepwise logistic regression analysis of clinical and radionuclide variables revealed that an abnormal (reversible or fixed) dipyridamole thallium-201 study was the single best predictor of cardiac events (relative risk 7.2, p less than 0.001). As has been demonstrated in younger patients, previous myocardial infarction (relative risk 1.8, p less than 0.001) and symptoms of congestive heart failure at presentation (relative risk 1.6, p = 0.02) were also significant independent clinical predictors of cardiac death or myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors report on a semiautomated program that incorporates both visual identification of fiducial points and digital determination of the ST-segment at 60 ms and 80 ms from the J point, ST slope, changes in R wave, and baseline drift. The off-line program can enhance the accuracy of detecting electrocardiographic (ECG) changes, as well as reproducibility of the exercise and postexercise ECG, as a marker of myocardial ischemia. The analysis program is written in Microsoft QuickBASIC 2.0 for an IBM personal computer interfaced to a Summagraphics mm1201 microgrid II digitizer. The program consists of the following components: (1) alphanumeric data entry, (2) ECG wave form digitization, (2) calculation of test results, (4) physician overread, and (5) editor function for remeasurements. This computerized exercise ECG digitization-interpretation program is accurate and reproducible for the quantitative assessment of ST changes and requires minimal time allotment for physician overread. The program is suitable for analysis and interpretation of large volumes of exercise tests in multicenter clinical trials and is currently utilized in the TIMI II, TIMI III, and BARI studies sponsored by the National Institutes of Health.

Exercise thallium scintigraphy is widely used to assess prognosis in patients with suspected or proven coronary artery disease. The incremental prognostic value of this technique in patients who have good exercise tolerance has not been well studied. Two hundred ninety-nine patients with known or suspected coronary artery disease without prior myocardial infarction or revascularization procedure referred for exercise myocardial perfusion imaging and able to exercise to greater than or equal to stage III of the Bruce protocol were included. After a mean follow-up of 50 +/- 10 months, there were 15 cardiac events (5%). The incidence of cardiac events was 10 versus 3% (p less than 0.001) in patients with an abnormal versus normal thallium-201 scan, and 9 versus 3% (p = 0.03) for an abnormal versus normal exercise electrocardiogram. When the 185 patients with a normal exercise electrocardiogram were examined, the incidence of cardiac events was 3% (5 of 150) in patients with a normal scan versus 0% (0 of 35) in patients with an abnormal scan. In the 114 patients with an abnormal exercise electrocardiogram, an abnormal thallium-201 scan was predictive of cardiac events (18% [8 of 44] versus 3% [2 of 70]; p = 0.006). Stepwise logistic regression analysis selected an abnormal thallium-201 scan and abnormal exercise electrocardiogram, low peak exercise heart rate, and male gender as independent variables associated with a significant increased risk of cardiac events. Thus, in patients with known or suspected coronary artery disease and good exercise tolerance, the addition of thallium-201 imaging in patients with an abnormal exercise electrocardiogram provides useful prognostic information.(ABSTRACT TRUNCATED AT 250 WORDS)

Traditional serial electrocardiogram (ECG) change classification schemes used in clinical trials such as the Minnesota Code rely on independent classification of the baseline and each follow-up or acute event ECG, whereby graded changes in the hierarchic severity level of the code signify new events such as myocardial infarction (MI). This approach suffers from classification errors caused by repeated instability at decision boundaries at each step when the baseline and each acute event ECG is classified, and various "verification rules" must be used at the end of the coding process to prevent trivial serial changes from causing large transitions in coded events. The NOVACODE algorithms for visual and computer coding of serial ECGs were designed to alleviate some of these instability problems by quantifying changes in critical waveform patterns on a continuous scale. This is achieved by determining, for each ECG coded, a Q-QS Score, ST Depression Score, ST Elevation Score and T-Wave Score, each ranging from 0 to 50. In the next step, a score is derived for ST-T evolution and this ST-T Evolution Score together with changes in Q-QS Score define criteria for a hierarchic mutually exclusive serial ECG change classification scheme that includes coding categories for Q-wave and non-Q wave MIs, equivocal Q wave evolution, evolving ischemic ST-T abnormalities, and various combinations of nonevolving Q-QS wave, and ST-T abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic value of exercise thallium-201 myocardial perfusion imaging has not been studied in an elderly (aged greater than or equal to 70 years) population. Retrospective analysis of 120 consecutive elderly patients undergoing Bruce protocol exercise stress with quantitative planar thallium-201 scintigraphy, followed clinically for a mean of 36 +/- 12 months after testing, revealed a 10% cardiac event rate (6 cardiac deaths from arrhythmia or congestive heart failure, and 5 fatal and 1 nonfatal myocardial infarction). There were no exercise stress-related complications. Survival without cardiac events was associated with greater exercise duration (5.6 +/- 2.4 vs 3.1 +/- 2.4 minutes; p less than 0.0007) and peak exercise heart rate (131 +/- 18 vs 120 +/- 19 beats/min; p less than 0.05). Univariate variables associated with higher cardiac event rates included: (1) peak exercise less than or equal to stage I (18 vs 6%; p = 0.04); (2) maximal ST-segment depression greater than or equal to 2 mm (27 vs 6%; p = 0.003); and (3) presence of a fixed or reversible thallium-201 perfusion defect (18 vs 2%; p = 0.004). Multivariate stepwise logistic regression analysis identified the combination of peak exercise less than or equal to stage I and any thallium-201 perfusion defect as the most powerful predictor of subsequent cardiac events (relative risk = 5.3 at 1 year). Thus, exercise thallium-201 scintigraphy in elderly patients is safe and provides important prognostic information.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained infarct artery patency is an important determinant of survival in patients with acute myocardial infarction. We studied 61 patients with acute myocardial infarction who received intravenous recombinant tissue-type plasminogen activator, aspirin or heparin within 6 hours of symptom onset, to determine if infarct artery patency after intravenous thrombolytic therapy influences myocardial electrical stability as measured by the prevalence of spontaneous ventricular ectopy or late potential activity. Infarct artery patency was determined by angiographic evaluation 2.5 +/- 3 days after infarction. Forty-eight patients (79%) had a patent infarct-related artery and 13 (21%) patients had an occluded vessel. The mean number of ventricular premature complexes (VPCs)/hour (p less than 0.01) and the prevalence of late potentials (54 vs 19%; p less than 0.03) were significantly higher in patients with an occluded versus patent-infarct related vessel. Although VPC frequency and late potentials were not influenced by the time to thrombolytic treatment, patients with a patent infarct-related artery had a lower prevalence of late potentials regardless of whether treatment was initiated less than or equal to 2 hours (25% patent vs 50% occluded; p = not significant) or 2 to 6 hours (16% patent vs 55% occluded; p greater than 0.03) after symptom onset. Thus, successful thrombolysis decreases the frequency of ventricular ectopic activity and late potentials in the early postinfarction phase. The reduction in both markers of electrical instability may help explain why the prognosis after successful thrombolysis is improved after acute myocardial infarction.

To evaluate the significance of ischemic ST depression without anginal chest pain during exercise testing among patients with diabetes mellitus, the data on 45 such patients from the Coronary Artery Surgery Study registry were analyzed. These patients (group 1, silent ischemia) were compared with 37 diabetic patients with both ischemic ST depression and chest pain (group 2, symptomatic ischemia), with 31 diabetic patients without ischemic ST depression or chest pain (group 3, no ischemia), and with 429 patients without diabetes who had silent ischemia during exercise testing. All patients had documented coronary artery disease (CAD) (greater than 70% diameter narrowing). The 6-year survival among patients with silent ischemia was worse in diabetic than nondiabetic patients (59 vs 82%, respectively, p less than 0.001). By contrast, the 6-year survival among patients without ischemia was similar among diabetic and nondiabetic patients (93 vs 85%, respectively, p = 0.476). Among diabetic patients, survival at 6 years with medical treatment was 59% for group 1, 66% for group 2 and 93% for group 3 (p = 0.008). Survival among subsets of patients with diabetes and silent ischemia (group 1) based on the extent of CAD and left ventricular function ranged from 100 to 32% (p = 0.093). The survival of the 45 patients with diabetes mellitus and silent ischemia (group 1) treated medically was compared with that of 28 patients receiving coronary artery graft bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients.

The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.

The average annual mortality in unselected patients with chronic stable angina is 4%. Mortality is increased in male patients and in patients who have risk factors such as hypertension, previous MI, or abnormal ECGs. We do not routinely recommend cardiac catheterization in the initial management of patients with stable angina unless the patient exhibits evidence for severe myocardial ischemia on non-invasive testing or has symptoms that are refractory to treatment. In patients who undergo cardiac catheterization, the most important determinant of survival is left ventricular function followed by the number of diseased vessels. Noninvasive testing provides important additional prognostic information to cardiac catheterization data and should be used in the decision to treat a patient medically or surgically. Mortality is increased in patients who have low exercise tolerance, exercise-induced ischemia, or a poor hemodynamic response to exercise. Unstable angina in medically treated patients is associated with a 3% to 5% hospital mortality and 7% to 8% mortality in the first year. The rate of nonfatal MI is about 8% to 10% in the first 2 weeks. We routinely recommend coronary angiography unless patients have had recent cardiac catheterization or there is a major contraindication. Mortality is increased in those who fail to respond to initial therapy, who have severe left ventricular dysfunction, and who have multivessel CAD, particularly left main CAD. The question of whether all patients with unstable angina require coronary angiography for risk stratification and possible revascularization is being addressed in the TIMI III trial.

Background: We report the results of the Heparin-Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction., Methods: Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay., Results: At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients assigned to heparin were patent, as compared with only 52 percent in the aspirin group (P less than 0.0001). Of the initially patent vessels, 88 percent remained patent after seven days in the heparin group, as compared with 95 percent in the aspirin group (P not significant). The numbers of hemorrhagic events (18 in the heparin and 15 in the aspirin group) and recurrent ischemic events (8 in the heparin and 2 in the aspirin group) were similar in the two groups., Conclusions: Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomitant low-dose oral aspirin. This observation has important implications for clinical practice and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy.

The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial.

Exercise electrocardiograms of 20 patients were analyzed using a customized software exercise electrocardiographic program and compared to measurements made by two cardiologists performing independent interpretations. The computerized program requires identification of the PQ junction, J point, and tracing of the ST-segment in three consecutive beats. The proportion of variance for J point, and ST 80 measurements was 0.93 and 0.90, respectively, when the same electrocardiogram was processed twice and analyzed by two separate cardiologists. The same 20 exercise electrocardiograms were analyzed by two other experienced cardiologists without computerized measurements. The proportion of variance was less at 0.73 and 0.76 for the J point and ST 80 measurements, respectively. The average amount of time required for the cardiologist to over read the computerized measurements was 2.7 +/- 1.5 minutes per ECG as compared to 20.7 +/- 11 minutes for the cardiologists who did not have computer-assisted measurements (p less than 0.0001). Thus, off-line computerized exercise electrocardiographic interpretation is highly reproducible, accurate, time-sparing for cardiologist over read function, and suitable for use in large-scale clinical trials.

Predischarge exercise testing after acute myocardial infarction (AMI) is an important noninvasive modality for risk stratification. To study the impact of position on cardiopulmonary exercise response, 30 patients performed symptom-limited upright treadmill and supine bicycle ergometry exercise an average of 8 days after an AMI. The exercise sequence was randomly assigned with a minimum 4-hour interval between tests. Exercise time and peak oxygen consumption were significantly greater in the upright position (7.0 +/- 2.0 vs 5.6 +/- 2.0 minutes; p less than 0.001 and 14.9 vs 12.0 ml/min/kg; p less than 0.001, respectively). Compared to the supine position, exercise in the upright position was associated with a significant increased incidence of ischemic exercise-induced ST-segment depression (33 vs 20%; p less than 0.03), and chest pain (20 vs 10%; p less than 0.04). Thus, position is an important determinant of myocardial ischemic response and exercise tolerance in patients who perform symptom-limited exercise tests early after AMI.

Patients with diabetes and end-stage renal failure are known to have a high risk for cardiac morbidity and mortality associated with renal transplantation. The most efficient method to determine preoperative cardiac risk has not been established. To determine the effectiveness of intravenous dipyridamole thallium imaging in predicting cardiac events, 40 diabetic renal transplant candidates were studied preoperatively in a prospective trial. The study group consisted of 40 patients whose average age was 42 years (range 27 to 64); 34 (85%) were hypertensive and 21 (53%) were cigarette smokers. Cardiac history included chest pain in 6 patients and prior myocardial infarction in 3 patients. Dipyridamole thallium imaging showed reversible defects in 9 patients, fixed defects in 8 patients and normal scans in 23 patients. Dipyridamole thallium imaging was performed using 0.56 mg/kg of dipyridamole infused intravenously over 4 minutes. Cardiac events occurred only in patients with reversible thallium defects, of which there were 6. Of these 6 patients, 3 had cardiac events before transplantation and 3 had them in the early postoperative phase (within 6 weeks of surgery). Of 21 patients who underwent renal transplantation, 3 had cardiac events within 6 weeks of transplantation. The average duration of follow-up was 11 months (range 1 to 21). Thus, dipyridamole thallium imaging is an effective method of identifying renal transplant candidates likely to develop cardiac complications. Routine coronary angiography may not be necessary to screen all renal transplant candidates for coronary artery disease before surgery.

The prognostic value of long-term risk stratification of patients with peripheral vascular disease who undergo intravenous dipyridamole thallium scintigraphy has not been well studied. We screened 131 patients with peripheral vascular disease who underwent intravenous dipyridamole thallium testing to determine cardiac event rates over an average follow-up of 18 +/- 10 months. Of the 131 patients, 111 subsequently had peripheral vascular surgery. The patients with abnormal thallium scans after dipyridamole had a significantly higher risk of death or myocardial infarction, both in the perioperative phase (7% versus 0%; p less than 0.001) and at late follow-up (17% versus 6%; p less than 0.01). The risk of a cardiac event was two-fold greater when a reversible as compared to a fixed thallium defect was present. Multivariate analysis selected the number of thallium segments with perfusion defects, prior history of angina pectoris, and chest pain during dipyridamole testing as perioperative predictors of a cardiac event. A reversible thallium defect was the only predictor of death or nonfatal myocardial infarction during late follow-up. Thus intravenous dipyridamole thallium scintigraphy is a useful noninvasive test for risk stratification of patients before peripheral vascular surgery and provides prognostic information as to the risk of a cardiac event in the 2-year period after the test. A reversible thallium defect is associated with a significant increased risk and would indicate that coronary angiography should be considered and preoperative coronary revascularization.

The TIMI phase II pilot study enrolled 288 patients with acute myocardial infarction who were treated with recombinant tissue plasminogen activator (rt-PA) within 4 hours of symptom onset and who were assigned to coronary angioplasty of the infarct-related vessel 18 to 48 hours after rt-PA treatment. The patients were followed to ascertain (1) vital status; (2) whether they suffered a recurrent myocardial infarction; (3) whether they received coronary angioplasty or bypass grafting; and (4) whether they were rehospitalized for a cardiac event. Risk factors for these events or combination of these events were identified and reported. The estimated 6-week, 6-month, and 1-year cumulative event rate of death or myocardial infarction was 9.1 +/- 1.7%, 12.9 +/- 2.0%, and 13.6 +/- 2.0%, respectively. With the exception of repeat hospital admissions, most of the above cardiac events occurred early during the patients' follow-up course. Cox proportional hazard analyses revealed that continuing chest pain after rt-PA administration, history of congestive heart failure, low systolic blood pressure at the time of initial evaluation, and history of hypertension increased the risk of death or recurrent myocardial infarction, while a history of chest discomfort at baseline evaluation and older age was predictive of future hospitalization or a revascularization procedure.

Intravenous dipyridamole is a relative selective coronary vasodilator which, when combined with thallium-201, provides a useful technique to assess myocardial perfusion. The intravenous dipyridamole is administered as an infusion at a rate of 0.14 mg/kg/min for 4 minutes. In the presence of significant coronary artery disease the increase of coronary blood flow is disproportionate between vessels with and without significant coronary lesions, providing the basis for detecting regional differences in flow using thallium-201. The test can be used alone or combined with low level exercise to increase test sensitivity. The test is safe when performed under medical supervision and when patient selection is done appropriately. Most of the side effects induced by dipyridamole infusion are well tolerated by patients and readily reversed with intravenous aminophylline and sublingual nitroglycerin. The average sensitivity and specificity of the dipyridamole thallium scintigraphy test from the major studies are 76% and 70%, respectively. The test is very useful in providing prognostic information in patients who are unable to exercise. A reversible thallium defect after dipyridamole infusion has been shown to be associated with significant mortality and morbidity in patients with documented or suspected coronary artery disease. The use of intravenous dipyridamole has been extended into other modalities of imaging, including 2-dimensional and Doppler echocardiography, to study functional changes in the left ventricular induced by the infusion of intravenous dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether exercise testing can identify higher risk patients with 3-vessel coronary artery disease (CAD) whose survival might be prolonged by coronary artery bypass grafting (CABG), the results of CABG were compared with those of medical therapy in 1,249 nonrandomized patients with 3-vessel CAD from the Coronary Artery Surgery Study (CASS) registry who underwent exercise testing. Analysis of 28 variables by Cox's regression model for survival revealed an independent effect of the left ventricular (LV) score, the final exercise stage, and treatment received on survival. Seven-year survival rates between medical and surgical therapy were compared among subsets of patients according to the LV function and the results of exercise testing. Among patients with normal LV function, those with at least 1 mm of ischemic ST-segment depression or low exercise capacity had better 7-year survival if treated by surgical rather than medical therapy (p less than 0.05). Survival was not different between the medical and surgical groups in patients without ischemic ST depression or with good exercise capacity. Among patients with impaired LV function, surgery improved survival in most subsets of patients with the exception of patients with a preserved exercise capacity. These results support the use of exercise testing in the risk stratification of patients with 3-vessel CAD.

Left main coronary artery disease (i.e., greater than or equal to 50% stenosis) was found in 1,477 of 20,137 patients in the Coronary Artery Surgery Study (CAS) registry. Of these patients, 53 (3.6%) were asymptomatic. Asymptomatic and symptomatic patients were similar in regard to 1) severity of left main coronary artery stenosis (67% vs. 70%), 2) extent of proximal coronary artery disease (no differences in number of or severity of proximal stenoses), 3) left ventricular end-diastolic pressure (13 mm Hg vs. 14 mm Hg), 4) left ventricular wall motion score 9.1 vs. 8.7), and 5) number of coronary artery segments with greater than 70% stenosis (4.4 vs. 4.8). Among the asymptomatic patients, 47% received medical and 49% received surgical treatment. In the symptomatic group, 20% received medical and 78% received surgical therapy. The survival rate 5 years after surgery for treatment of left main coronary artery stenosis was 84% for the symptomatic patients and 88% for the asymptomatic patients (p = NS). Medical management of left main coronary artery disease produced a 5-year survival rate of 57% for asymptomatic patients and 58% for symptomatic patients. Within the asymptomatic subgroup, 88% of those surgically treated survived 5 years, whereas only 57% of those medically treated survived 5 years (p = 0.02). Thus, for CASS patients with left main coronary artery disease, the percentage of those that were asymptomatic is low (3.6%); asymptomatic and symptomatic patients with left main coronary artery disease had no significant difference in severity of left main coronary artery stenosis, extent of overall coronary artery disease, or left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Thallium perfusion imaging following the intravenous infusion of dipyridamole, a potent coronary vasodilator, has been demonstrated to be useful in the evaluation of the functional significance of coronary artery disease (CAD). While recent studies have demonstrated that 2-dimensional echocardiographic monitoring of left ventricular (LV) function after intravenous dipyridamole has a sensitivity somewhat less than that of thallium perfusion imaging, none has examined the usefulness of Doppler evaluation of aortic blood flow in this setting. One hundred patients undergoing dipyridamole-thallium imaging for clinical indications were studied. Technically adequate Doppler echocardiographic studies were obtained in 97 patients. LV ejection fraction, peak aortic velocity and acceleration, as well as segmental LV wall motion, were analyzed before and at peak dipyridamole effect. Thallium perfusion images were normal in 41 and abnormal in 53 patients studied. A statistically significant difference in percent change from baseline to peak dipyridamole effect in velocity, acceleration and ejection fraction was seen between the 2 groups (26 vs -2%, 51 vs -2% and 16 vs 4%, respectively, all p less than 0.05). Comparison of 2-dimensional wall motion analysis to thallium yielded a sensitivity and specificity of 74 and 80%, respectively. In the group of patients who underwent cardiac catheterization, 2-dimensional wall motion analysis yielded a sensitivity of 64% in the detection of CAD. The combination of 2-dimensional and Doppler echocardiographic parameters increased the sensitivity in the detection of CAD to 85%.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether exercise testing can identify patients whose survival might be prolonged by coronary artery bypass surgery, the results of bypass surgery were compared with those of medical therapy alone in 5,303 nonrandomized patients from the Coronary Artery Surgery Study registry who underwent exercise testing. Patients in the two treatment groups differed substantially with regard to important baseline variables. Analysis of 32 variables by Cox's regression model for survival revealed an independent beneficial effect of bypass surgery on survival (p less than 0.00001). Patients were then stratified into subsets according to the results of exercise testing. Surgical benefit was greatest in the 789 patients who exhibited at least 1 mm of ST segment depression and who could exercise only into stage 1 or less. Among the 398 patients with three vessel coronary disease showing these characteristics, 7 year survival was 58% for the medical group and 81% for the surgical group (p less than 0.001). There was no difference in survival between the surgical and medical groups among the 1,545 patients without ischemic ST segment depression who were able to exercise into stage 3 or greater. Thus, in patients who demonstrate ischemia on exercise testing and whose exercise capacity is limited, coronary bypass surgery appears to improve survival in comparison with medical therapy alone.

Exercise tolerance 1, 3 and 8 hours after 80 mg of propranolol, 120 mg of diltiazem and 20 mg of nifedipine, and after 20 minutes of 0.6 mg of sublingual nitroglycerin were compared with placebo in 15 men who had chronic stable angina pectoris. Three hours after drug ingestion, the exercise time was prolonged by 72 +/- 26, 162 +/- 27 and 161 +/- 30 seconds (p less than 0.05) for propranolol, diltiazem and nifedipine, respectively, and by 123 +/- 35 seconds (p less than 0.001) 20 minutes after sublingual nitroglycerin compared with placebo. The onset of ST-segment depression greater than or equal to 0.1 mV was delayed by 120 +/- 34, 203 +/- 29 and 189 +/- 35 seconds (p less than 0.05) and by 79 +/- 23 seconds (p less than 0.05), respectively. After propranolol, the peak rate-pressure product decreased compared with placebo (15.1 +/- 1.1 U [10(-3)] vs 20.0 +/- 1.5 U, p less than 0.01). In contrast, the peak rate-pressure product was greater after diltiazem and nifedipine than after placebo (22.2 +/- 1.3 U [p less than 0.05] and 23.8 +/- 1.4 U [p less than 0.01]). The maximal increase in exercise tolerance was most marked for each drug at 3 hours, but was also significant at 1 hour for nifedipine and at 8 hours for diltiazem. At 3 hours, an increase in exercise time of more than 2 minutes was observed in 4 of 6 patients who had plasma propranolol concentrations greater than 40 ng/ml, 8 of 9 who had a plasma diltiazem concentration greater than 150 ng/ml, and in 7 of 7 who had a plasma nifedipine concentration greater than 90 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the usefulness of exercise echocardiography in the follow-up of patients after percutaneous transluminal coronary angioplasty (PTCA), we studied 56 patients at rest and immediately following exercise with two-dimensional echocardiography. Sixty-nine of 73 stress/echo studies (94%) were suitable for interpretation. Seventeen patients (group I) with significant coronary artery disease (CAD) were studied before and after PTCA. Sixteen patients with coronary disease not undergoing PTCA (group II) and 23 individuals without significant coronary disease (group III) served as age-matched controls. Left ventricular ejection fraction did not change significantly in group I patients prior to PTCA (56 +/- 7 versus 54 +/- 12, p = ns) or in group II patients (52 +/- 10 versus 56 +/- 15, p = ns), rest versus immediate after exercise measurements. Following angioplasty, left ventricular ejection fraction increased in group I patients from 55 +/- 7 to 65 +/- 8, p less than 0.001 from rest to exercise, and to a similar extent in group III individuals (55 +/- 6 to 66 +/- 8, p less than 0.001). Electrocardiographic (ECG) evidence of ischemia (greater than 1 mm ST segment depression) was found in 13 of 17 group I patients prior to PTCA and in 8 of 16 group II patients (CAD). None of the 25 normal patients and four of the group I patients following PTCA had abnormal ECG changes with exercise. New exercise-induced echocardiographic wall motion abnormalities were found in 12 of 17 group I patients prior to PTCA and in none of the group I patients following PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy.

Between March 1975 and March 1980, 50 patients aged 70 to 78 years underwent open-heart surgery at the Montreal Heart Institute. Coronary bypass was performed in 23 patients, valve replacement in 16 and combined coronary and valve surgery in 11. There were four early deaths, all due to cardiac causes. Early postoperative complications occurred in 58% of the patients. There were seven late deaths, five in the valve replacement groups and two in the isolated coronary bypass group. The cumulative survival rate 5 years after surgery was estimated at 76%. While 82% of the survivors were in functional class III or IV before surgery, 90% were in class I or II when last seen, after an average postoperative follow-up of 3 years. Nonfatal late complications occurred in eight of the survivors, one of whom suffered a major hemorrhage due to anticoagulant therapy. Thus, open-heart operations can be offered to the elderly, with a low risk of operative death. The late clinical improvement, with a return to a normal lifestyle, justifies a surgical approach for patients in otherwise good general condition.

Combined proximal left anterior descending and proximal left circumflex, or "left main equivalent" (LMEQ), disease defines a prognostic angiographic high-risk patient population. We assessed the effect of coronary bypass surgery compared with medical therapy in 903 patients with LMEQ disease by stratified life table and Cox regression analysis. The 5 year survival rates of the 639 and 264 patients who received surgical vs medical therapy was 85% vs 55%, respectively (p less than .001). Analysis of patient subsets stratified by age, angina class, right coronary disease, and ejection fraction revealed a significant survival benefit for surgically treated patients in most strata. Cox regression analysis revealed improved survival for surgically treated patients after adjustment for important baseline variables known to influence prognosis. Surgically treated patients had significantly less angina and need for antianginal drugs compared with the medically treated group. When the Coronary Artery Surgery Study randomized and randomizable LMEQ patients were analyzed, coronary bypass surgery improved 5 year survival when preoperative ejection fraction was under 0.50 but not when ejection fraction was 0.50 or higher. Thus coronary bypass surgery prolongs and improves quality of life (as defined by angina status and need for antianginal drugs) in most patients with LMEQ disease but does not appear to improve 5 year survival in a small subset of LMEQ patients who are asymptomatic after myocardial infarction or who have mild chronic stable angina and are under age 65 with well-preserved left ventricular function.

We tested the effectiveness and safety of i.v. diltiazem in the management of paroxysmal supraventricular tachyarrhythmias in 39 patients, 21 with organic heart disease and seven in heart failure. Fifteen patients presented with supraventricular tachycardia, 12 with atrial fibrillation and 12 with atrial flutter. End points were conversion to sinus rhythm or slowing of the ventricular rate to 100 beats/min or less. Diltiazem was given as an i.v. bolus of either 150 or 300 micrograms/kg over 2 minutes. A second injection was administered to patients who received the lower dose and failed to reach either end point within 30 minutes. The overall success rate was 82% (32 of 39 patients). Time to end point was 5 minutes or less in 20 patients. Conversion to sinus rhythm occurred in 13 of 15 patients (87%) with supraventricular tachycardia and in two of 12 patients with atrial fibrillation. Treatment side effects included a slow ventricular rate in one patient who had a sick sinus syndrome and hypotension in two patients that rapidly responded to fluid administration. We conclude that i.v. diltiazem is effective and well tolerated and advocate its use in the management of paroxysmal supraventricular tachyarrhythmias.

Patients with atherosclerotic cardiovascular disease may be adversely affected by the presence of carboxyhemoglobin, even at low concentrations. We investigated the effects of carbon monoxide exposure on myocardial ischemia during exercise in 63 men with documented coronary artery disease. On each test day, subjects performed two symptom-limited incremental exercise tests on a treadmill; the tests were separated by a recovery period and 50 to 70 minutes of exposure to either room air or air containing one of two concentrations of carbon monoxide (117 +/- 4.4 ppm or 253 +/- 6.1 ppm). The order of exposure was assigned randomly. On each occasion, neither the subjects nor the study personnel knew whether the subjects had been exposed to room air or to one of the concentrations of carbon monoxide. Exposure to room air resulted in a mean carboxyhemoglobin level of 0.6 percent, exposure to the lower level of carbon monoxide resulted in a carboxyhemoglobin level of 2.0 percent, and exposure to the higher level of carbon monoxide resulted in a level of 3.9 percent. An effect of carbon monoxide on myocardial ischemia was demonstrated objectively by electrocardiographic changes during exercise. We observed a decrease of 5.1 percent (90 percent confidence interval, 1.5 to 8.7 percent; P = 0.02) and a decrease of 12.1 percent (90 percent confidence interval, 9.0 to 15.3 percent; P less than or equal to 0.0001) in the length of time to a threshold ischemic ST-segment change (ST end point) after carbon monoxide exposures that produced carboxyhemoglobin levels of 2.0 percent and 3.9 percent, respectively. The length of time to the onset of angina decreased by 4.2 percent (90 percent confidence interval, 0.7 to 7.9 percent; P = 0.054) at the 2.0 percent carboxyhemoglobin level and by 7.1 percent (90 percent confidence interval, 3.1 to 10.9 percent; P = 0.004) at the 3.9 percent carboxyhemoglobin level. Significant dose-response relations were found in both the change in the length of time to the ST end point (P less than or equal to 0.0001) and the change in the length of time to the onset of angina (P = 0.02). We conclude that low levels of carboxyhemoglobin exacerbate myocardial ischemia during graded exercise in subjects with coronary artery disease.

The objective of this study was to evaluate the impact on survival of the anatomic extent of obstructive coronary artery disease and of two measures of left ventricular (LV) performance. This study is based on 20,088 patients without previous coronary artery bypass graft surgery who were enrolled in the registry of the National Heart, Lung, and Blood Institute Coronary Artery Surgery Study from 1975 to 1979. The cumulative 4-year survival of medically managed patients was analyzed to determine the survival of specific subsets of patients with obstructive coronary disease. The vital status of 99.8% of the patients was known. The 4-year survival of medically treated patients with no significant obstructive disease was 97%, in contrast to 92%, 84% and 68% in patients with one-, two- and three-vessel disease, respectively. The presence of left main coronary artery disease decreased survival significantly. The 4-year survival decreased from 70% to 60% in patients with three-vessel disease when significant obstruction of the left main coronary artery was also present. Patients with significant coronary artery disease who had an ejection fraction of 50--100%, 35--49%, and 0--34% had a 4-year survival of 92%, 83% and 58%, respectively. The systolic contraction pattern was assessed in five selected segments and given a score of 1--6, with a score of 1 for normal function, increasing to 6 if an aneurysm was present. In a patient with normal LV contraction in all five segments of the LV ventricular angiogram, the LV score would equal 5. Patients with an LV score of 5--11, 12--16 and 17--30 had 4-year survivals of 90%, 71% and 53%, respectively. Patients with good LV function (a score of 5--11) had a 4-year survival of 94%, 91% and 79% for one-, two- and three-vessel disease, respectively. Patients with poor left ventricular function (score of 17--30) had a 4-year survival rate of 67%, 61% and 42% in one-, two- and three-vessel disease, respectively. Thus, LV function is a more important predictor of survival than the number of diseased vessels.

In order to evaluate survival patterns in patients with left main coronary artery (LMCA) disease, 1492 patients with LMCA disease admitted to the U. S. Collaborative Study on Coronary Artery Surgery (CASS) were followed up. Of the 1492 patients, 1183 (79%) underwent coronary artery bypass (CABG) with an operative mortality of 4.2% and an average of 2.7 grafts/patient inserted. Allocation to surgery was by patient and physician preference and not random. Surgical patients generally had more severe angina, a higher prevalence of beta blocker usage, worse ventricular function and more severe LMCA stenosis than medically treated patients. Overall (4 years) survival of the surgical group was 88% compared to 63% in the medical group (p less than 0.001). Other independent predictors of mortality included angiographic left ventricular (LV) dysfunction score, age, % LMCA stenosis, hypertension, dominance, and presence of significant right coronary artery (RCA) stenosis greater than or equal to 50%. CABG was not shown to significantly improve survival in women, in LMCA patients with left dominant circulation, in LMCA patients with non-diseases dominant or balanced RCA circulation or in LMCA patients with greater than or equal to 50% RCA stenosis but good LV function. These data indicate that CABG prolongs life in most patients with left main coronary artery disease, particularly those with severe LMCA narrowing or severe LV dysfunction, however, subgroups of LMCA patients are identifiable who may fare with medical treatment alone.

Baseline, clinical, and angiographic features of 1014 Coronary Artery Surgery Study (CASS) registry patients with combined proximal left anterior descending and proximal left circumflex coronary disease were examined to define determinants of prognosis in this clinical high-risk patient subset. A stepwise Cox regression analysis identified congestive heart failure score, left ventricular contraction score, mitral regurgitation, age, and digitalis usage as independent variables predictive of 8-year survival. When patients were stratified by left ventricular contraction score, the 8-year survival rate was 62%, 49%, and 19%, respectively, for patients with a left ventricular score of 5 to 9, 10 to 14, and greater than or equal to 15 (p less than 0.0001). The presence of a stenosis greater than or equal to 70% in the right coronary artery was associated with worse survival (47% versus 54% at 8 years; p = 0.051). In conclusion, the diagnosis of combined proximal left anterior descending and left circumflex coronary artery disease represents a large prognostic spectrum that needs to be considered when counselling individual patients.

One hundred seven asymptomatic patients who underwent intravenous dipyridamole thallium imaging were evaluated to determine prognostic indicators of subsequent cardiac events over an average follow-up period of 14 +/- 10 months. Univariate analysis of 18 clinical, scintigraphic and angiographic variables revealed that a reversible thallium defect, a combined fixed and reversible thallium defect, number of segmental thallium defects and extent of coronary artery disease were significant predictors of subsequent cardiac events. Of the 13 patients who died or had a nonfatal infarction, 12 had a reversible thallium defect. Stepwise logistic regression analysis selected a reversible thallium defect as the only significant predictor of cardiac events. When death or myocardial infarction was the outcome variable, a combined fixed and reversible thallium defect was the only predictor of outcome. In patients without previous myocardial infarction, the cardiac event rate was significantly greater in those with an abnormal versus normal thallium scan (55% versus 12%, p less than 0.001). Thus, intravenous dipyridamole thallium scintigraphy is a useful noninvasive test to risk stratify asymptomatic patients with coronary artery disease. A reversible thallium defect most likely indicates silent myocardial ischemia in a sizable fraction of patients in this clinical subset and is associated with an unfavorable prognosis.

The prognostic value of early exercise testing after successful coronary angioplasty was determined in 196 and 225 consecutive patients with single-vessel and multivessel coronary disease, respectively, who underwent a symptom-limited exercise test within 30 days of the procedure. The incidence of exercise-induced ST segment depression greater than or equal to 1 mm was significantly greater in patients with multivessel versus single-vessel disease (27% versus 14%; p less than 0.005) and in patients with multivessel coronary disease who had incomplete versus complete revascularization (36% versus 10%; p less than 0.001). An abnormal exercise ECG result was associated with a significantly increased risk of cardiac events in patients with multivessel disease but not in patients with single-vessel disease. Exercise-induced angina occurred in a small and similar proportion of patients with single and multivessel coronary disease (8% versus 12%). The presence of exercise-induced angina was associated with a higher incidence of follow-up cardiac events in patients with multivessel disease and incomplete revascularization (52% versus 33%; p less than 0.05). Exercise duration was significantly less in patients with multivessel disease who had a subsequent cardiac event compared with that in patients who did not have such an event (458 +/- 168 versus 519 +/- 156 seconds; p = 0.01). Thus an abnormal exercise ECG finding within 1 month of successful coronary angioplasty is predictive of subsequent cardiac events in patients who have multivessel disease. The prognostic content of the test might be further improved if the test were performed several months after the procedure when the risk of restenosis is greatest.

The working status of 1165 patients aged 59 years or less (mean 49.8 years) was evaluated 7 to 77 months (mean 36 months) after aortocoronary bypass surgery. Although 76% of the patients eventually returned to work, only 56% were working 6 months after their operation. The proportion of patients working peaked at 2 years after the operation (at 66%) and decreased progressively to 56% at 4 years and 53% at 5 years without ever reaching the proportions that applied 12 and 6 months before the operation (84% and 69% respectively). Multivariate analysis identified three socioeconomic and three clinical variables as predicting the working status at 6 months and at yearly points during the first 4 years after the operation. Of the socioeconomic variables analysed, preoperative unemployment of long duration, a preoperative occupation that required strenuous physical effort and a low level of education were, in that order, the strongest predictors of postoperative unemployment. Among the clinical variables, associated noncardiovascular illness and the severity and duration of angina pectoris independently influenced the patients' post-operative working status. The authors conclude that modification of some of these variables should by attempted both before and after aortocoronary bypass surgery to see whether the rate of return to employment after the operation can be improved in selected patients.

Determination of the restenosis rate after multilesion percutaneous transluminal coronary angioplasty is an important consideration in defining expanded indications for the procedure. Of 209 patients who underwent successful multilesion coronary angioplasty, 55 symptomatic and 74 asymptomatic patients were restudied an average of 7 +/- 4 months after dilation. The restenosis rate was 82% (45 of 55) in the symptomatic patients and 30% (22 of 74) in the asymptomatic patients (p less than 0.001). Only 4% of the asymptomatic patients had restenosis at more than one dilation site. When only patients who developed a restenosis were considered, the restenosis occurred at more than one dilation site in 47% (21 of 45) of the symptomatic group versus 14% (3 of 22) of the asymptomatic group (p less than 0.05). When all recurrent stenoses were examined, the severity of the luminal narrowing was greater than or equal to 70% in 64% (45 of 70) of the stenotic lesions in the symptomatic patients versus 31% (8 of 26) of the stenotic lesions in the asymptomatic patients (p less than 0.05). Proximal left anterior descending coronary artery disease, increased length of the stenotic narrowing, male gender and diabetes were associated with an increased incidence of restenosis by multivariate analysis. Patient-related variables were not predictive of multilesion restenosis. In conclusion, the majority of patients are clinically improved after multilesion coronary angioplasty. Recurrent symptoms after multilesion coronary angioplasty are frequently associated with multilesion restenosis and a more severe degree of restenotic narrowing. Restenosis at more than one dilation site is uncommon in the asymptomatic patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent advances in Doppler echocardiography have made possible noninvasive determination of stroke volume, cardiac output and peak ejection velocity at rest. To determine the ability of Doppler to measure these variables and the effect of altered left ventricular (LV) function during upright treadmill exercise, 20 normal subjects (group I) and 17 patients with coronary artery disease (CAD) (group II) were studied. Stroke index response was similar in both groups. The increase in cardiac index was more rapid in group I subjects and reached a higher peak value at maximal exercise (8.6 +/- 2.5 vs 5.5 +/- 2.2 liters/min, p less than 0.001). Peak ejection velocity increased rapidly during exercise in group I subjects; it increased much less in group II patients. Differences were significant at each stage of exercise. Peak ejection velocity was 1.56 +/- 0.32 and 0.89 +/- 0.26 m/s in group I vs group II patients, respectively, at maximal exercise. Three responses were seen in group II subjects. Three patients, all with 1-vessel CAD and normal LV function at rest, showed a normal response, with an increase in peak ejection velocity of at least 80% (type I response). In 8 patients peak ejection velocity increased less than 80% (type II response) and in 6 patients it decreased at maximal exercise (type III). Type II and III responses were seen in patients with more severe CAD and LV dysfunction at rest. These data show a progressive difference in Doppler-derived variables in exercise between normal subjects and patients with CAD, which is greatest in patients with LV dysfunction at rest and multivessel CAD.

Introduction of a reliable method for continuous monitoring of mixed venous oxygen saturation has focused attention on the therapeutic and prognostic implications of this value. It is generally agreed that mixed venous oxygen saturation in the 40 to 60 percent range is associated with substantial patient morbidity and mortality if not rapidly corrected. However, several patients with chronic low cardiac output syndrome who have had mixed venous oxygen saturation of less than 40 percent for prolonged periods of time and who have not had decompensation were observed. Three representative patients with these findings are described and mechanisms put forth that may account for the observed relations between mixed venous oxygen saturation and mortality in these and other patients.

The impact of age on hospital mortality, incidence of major hemorrhagic events and transfusion requirements was examined in 756 patients with acute myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) Phase I, open label studies and the TIMI Phase II pilot study. The mortality rate significantly increased with age and was 3.5%, 11.5% and 12% in patients less than 65, 65 to 69 and 70 to 76 years of age, respectively (p less than 0.001). Logistic regression analyses selected female gender, diabetes mellitus, extensive coronary artery disease, history of congestive heart failure, continuing chest pain immediately after recombinant tissue-type plasminogen activator (rt-PA) administration, low systolic blood pressure at the time of admission and advanced age as variables predictive of in-hospital death. The incidence of major hemorrhagic events among patients not undergoing cardiac surgery during hospitalization was 8.7%, 14.5% and 24.7% in patients aged less than 65, 65 to 69 and greater than or equal to 70 years, respectively (p less than 0.001). The majority of hemorrhages were secondary to cardiac catheterization or puncture wounds. Variables related to a major hemorrhagic event included protocol, age, rt-PA dose/kg body weight and elevated diastolic blood pressure on admission. Of five intracranial bleeding events, three occurred in patients greater than 65 years. Transfusion requirements significantly increased with age (p less than 0.001). Reperfusion status at 90 min in the TIMI Phase I and open label studies A to C was similar in the three age groups studied and ranged from 60% to 71%.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated junctional S-T depression induced during treadmill exercise testing was correlated with coronary arteriographic findings in 230 patients. Of 75 patients with junctional depression of less than 1.5 mm, 10 had 50% or greater stenosis of at least one major coronary artery and 2 patients (3%) had multivessel disease. Of 42 with junctional depression of 1.5 mm or more and a rapid upsloping S-T segment, 23 had 50% or greater coronary stenosis and 12 of these had multivessel disease. Of 35 with an upsloping pattern (junctional depression of more than 2 mm, upsloping S-T segment depressed 2 mm or more, 0.08 second after the J point), 33 (94%) had 50% or greater coronary stenosis compared with 46 (96%) and 30 (97%) with 2 mm or more junctional depression ahd a horizontal or downsloping S-T segment. In conclusion, multivessel disease is rare with isolated exercise-induced junctional depression of less than 1.5 mm but common when the J point is depressed 1.5 mm or more. Junctional depression of more than 2 mm is associated with the same incidence of coronary disease when the S-T segment is slowly ascending (upsloping pattern) as when it is horizontal.

Most patients who are considered candidates for coronary angioplasty should have objective evidence of myocardial ischemia confirmed before the procedure, if clinically possible. In patients with progressive unstable angina, for whom exercise testing is inappropriate, the location of transient resting ECG changes should be looked for on the 12-lead ECG. In clinically stable patients with 1-vessel coronary disease, a pre-PTCA exercise test without radionuclides would suffice for most patients. In the initial months after PTCA, persistence or the return of an ischemic response similar to that observed before the procedure would indicate restenosis. Disease progression in other vessels during the year after the PTCA procedure would be uncommon compared to the incidence of restenosis. In all other stable patients, exercise ECG should be combined with thallium-201 scintigraphy to provide a more useful evaluation of angioplasty results. If only a single vessel is dilated, the importance of the remaining coronary disease may be demonstrated and may influence the clinical decision as to whether further intervention is needed. Dilatation of occluded vessels is occasionally attempted in patients with multivessel coronary disease. The incidence of restenosis is slightly greater (40%) in the months after PTCA than in a stenotic nonoccluded vessel. Multilesion dilatation can also be associated with restenosis at more than one site, and the use of thallium scintigraphy may be helpful in assessing which region of the myocardium is ischemic. As dilatation is performed more frequently in patients with multivessel disease, coronary angiography will remain the 'gold standard' to answer questions about recurrence or progression of the disease, and against which to compare results of noninvasive tests. All exercise tests should be performed without cardioactive medication if possible, and the test should be a sign- or symptom-limited test. The elective exercise test in an asymptomatic individual after PTCA should be performed between 1 and 2 weeks to serve as a baseline for future follow-up. In patients who develop restenosis, symptomatic status will often suggest a PTCA failure. In asymptomatic patients or those with atypical symptoms, the exercise thallium study will often be useful.

To determine whether coronary artery bypass surgery would prolong survival in patients with silent myocardial ischemia during exercise testing, the data on 692 such patients from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients were followed up for up to 7 years after medical (n = 424) or surgical (n = 268) therapy. Stratification of patients into subsets was based on the results of cardiac catheterization. Surgical benefit was greatest in the patients with three vessel coronary artery disease or abnormal left ventricular function. Among the 75 patients with three vessel coronary disease and left ventricular dysfunction, the 7 year survival rate was 37% for the medical group and 90% for the surgical group (p less than 0.0001). Thus, among patients with silent myocardial ischemia during exercise testing in this nonrandomized study, survival appeared to be enhanced by coronary artery bypass surgery in subsets of patients with severe coronary artery disease and abnormal left ventricular function.