Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release: results from the GUARDIAN trial.

OBJECTIVES: We sought to determine if elevated cardiac serum biomarkers after coronary artery bypass graft surgery (CABG) are associated with increased medium-term mortality and to identify patients that may benefit from better postoperative myocardial protection. BACKGROUND: The relationship between the magnitude of cardiac serum protein elevation and subsequent mortality after CABG is not well defined, partly because of the lack of large, prospectively studied patient cohorts in whom postoperative elevations of cardiac serum markers have been correlated to medium- and long-term mortality. METHODS: The GUARD during Ischemia Against Necrosis (GUARDIAN) study enrolled 2,918 patients assigned to the entry category of CABG and considered as high risk for myocardial necrosis. Creatine kinase-myocardial band (CK-MB) isoenzyme measurements were obtained at baseline and at 8, 12, 16 and 24 h after CABG. RESULTS: The unadjusted six-month mortality rates were 3.4%, 5.8%, 7.8% and 20.2% for patients with a postoperative peak CK-MB ratio (peak CK-MB value/upper limits of normal [ULN] for laboratory test) of < 5, > or = 5 to <10, > or =10 to < 20 and > or =20 ULN, respectively (p < 0.0001). The relationship remained statistically significant after adjustment for ejection fraction, congestive heart failure, cerebrovascular disease, peripheral vascular disease, cardiac arrhythmias and the method of cardioplegia delivery. Receiver operating characteristic curve analysis revealed an area under the curve of 0.648 (p < 0.001); the optimal cut-point to predict six-month mortality ranged from 5 to 10 ULN. CONCLUSIONS: Progressive elevation of the CK-MB ratio in clinically high-risk patients is associated with significant elevations of medium-term mortality after CABG. Strategies to afford myocardial protection both during CABG and in the postoperative phase may serve to improve the clinical outcome.

Association between new electrocardiographic abnormalities after coronary revascularization and five-year cardiac mortality in BARI randomized and registry patients.

There are few data comparing the relative frequency of new electrocardiographic (ECG) abnormalities after coronary artery bypass grafting (CABG) compared with percutaneous transluminal coronary angioplasty (PTCA) and their association with long-term cardiac mortality. The study population consisted of 3,373 patients who were either randomized or eligible to be randomized to CABG or PTCA in the BARI trial. The frequency of new postprocedural ECG abnormalities was significantly greater after a CABG procedure than after PTCA. The incidence of new postprocedural major Q waves, ST-segment elevation, and T-wave abnormalities were significantly more frequent after CABG. After PTCA (n = 1,869), the 5-year cardiac mortality rates associated with the new development of major Q waves, ST-segment elevation, ST-segment depression, T-wave abnormalities, or no abnormality was 18.1%, 8.5%, 8.9%, 6.0%, and 5.4%, respectively. After CABG (n = 1,427), 5-year cardiac mortality rates were 8.0%, 4.2%, 3.8%, 2.8%, and 3.7%, respectively. The adjusted relative risk of 5-year cardiac mortality for new Q-wave abnormalities was 2.6 after CABG (p <0.04) and 4.6 after PTCA (p <0.01). Thus, patients who undergo CABG have more postinitial procedural ECG abnormalities than patients who undergo PTCA. Cardiac mortality is significantly increased by the new development of postprocedural Minnesota code Q-wave abnormalities regardless of whether patients undergo CABG or PTCA.

Right bundle branch block as a cause of false-negative ECG classification of inferior myocardial infarction.

It is generally accepted in clinical electrocardiography that a right bundle branch block (RBBB) does not interfere with the electrocardiographic (ECG) diagnosis of myocardial infarction (MI). The basic assumption is that the initial excitation wavefronts are relatively unchanged in RBBB. This study compared serial changes in Q wave duration in inferior leads II, III, and aVF in 9 patients who developed RBBB within 3 weeks after myocardial revascularization procedure (RBBB group) and in 41 revascularized patients without RBBB in the same observation period (control group). Q wave durations in the electrocardiograms obtained before the patients' procedures were not significantly different between the study and control groups. However, Q wave durations shortened significantly more in the RBBB group than in the control group. The most pronounced Q wave duration shortening took place in lead aVF, -18.2 ms in the RBBB group versus -3.8 ms in the control group (P = .0001). The shortening was less pronounced, although significant, in leads II and III: II, -7.6 +/- -10.9 ms in the RBBB group vs -2.3 +/- -3.5 ms in the control group (P = .01); III, -11.3 +/- -10.5 ms vs -2.6 +/- -6.5 ms (P = .002); aVF, -18.2 +/- -13.5 ms vs -3.8 +/- -5.3 ms (P < .0001). It is concluded that incident RBBB complicating revascularization procedures may cause significant alterations in spatial orientation of the initial excitation wavefronts. This may be a potential source of false-negative ECG diagnosis of inferior MI, particularly in clinical trials where serial ECG analysis is an important part in MI classification.

Myocardial infarction and cardiac mortality in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial.

BACKGROUND: Cardiac mortality and myocardial infarction (MI) rates are used to evaluate the efficacy of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We compared 5-year cardiac mortality and MI rates in 1829 patients with multivessel disease randomized to CABG or PTCA. METHODS AND RESULTS: The 5-year cardiac mortality rate was 8.0% in patients assigned to PTCA compared with 4.9% in those assigned to CABG (relative risk [RR] of 1.55 with a 95% confidence interval [CI] of 1.07 to 2.23; P=.022). In a subgroup of 1476 nondiabetic patients, there were no significant differences between treatment groups in cardiac mortality either overall (4.6% versus 4.2%; RR= 1.04, 95% CI, 0.65 to 1.66; P=.908) or in subgroups based on symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. The two treatment groups had similar event rates for the combined end point of cardiac death or MI. The RR for cardiac mortality in 264 patients who sustained an MI compared with those who did not was 5.9 (P<.001). MIs were more common after CABG during index hospitalization (P=.004), but in the PTCA group, they were more common after discharge (P<.001). CONCLUSIONS: The Bypass Angioplasty Revascularization Investigation (BARI) trial indicates 5-year cardiac mortality in patients with multivessel disease was significantly greater after initial treatment with PTCA than with CABG. The difference was manifest in diabetic patients on drug therapy. There were no significant differences overall for the composite end point of cardiac mortality or MI between treatment groups or for cardiac mortality in nondiabetic patients regardless of symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery.

Methodology of serial ECG classification using an adaptation of the NOVACODE for Q wave myocardial infarction in the Bypass Angioplasty Revascularization Investigation (BARI).

Serial electrocardiographic (ECG) changes are a critical component of the diagnostic algorithm for classification of myocardial ischemic events in large-scale clinical trials. This study describes a computerized serial ECG classification program developed at the St. Louis University Core ECG Laboratory for use in the Bypass Angioplasty Revascularization Investigation (BARI) trial, in which patients with multivessel coronary artery disease were randomized to receive either coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. The St. Louis University program detects and codes serial changes in Q, ST, and T wave items according to Minnesota code (MC) criteria using a modified NOVACODE hierarchical classification system. Measurements using a seven-power calibrated coding loupe are used to generate the MC from a customized software program. Significant minor or major changes are detected by the serial comparison program and referred to a physician coder for verification. Serial comparison coding rules are used to adjust for weaknesses in the standard MC classification system resulting from instability at decision boundaries. Of 4,244 BARI randomized and registry study participants with follow-up ECGs received at the Core ECG Laboratory as of March 1995, a grade 2 MC Q wave progression was noted in 568 participants (13.4%) using MC criteria alone, as compared with 367 (8.6%) after the St. Louis University coding rules were applied. The incidence of grade 1 MC Q wave progressions was 16.4% (697/4,244) versus 6.1% (259/4,244) when the St. Louis University program was applied. Intraobserver variability for grade 2 Q wave progression codes determined from a sample of 812 serial.

Determination of perioperative cardiac risk by adenosine thallium-201 myocardial imaging.

To determine the predictive value of adenosine thallium-201 myocardial imaging for perioperative cardiac events, 60 consecutive patients referred for preoperative cardiac evaluation were studied before vascular (n = 25), orthopedic (n = 14), or general (n = 21) surgery. Tomographic (n = 52) and planar (n = 8) thallium-201 imaging was performed after adenosine infusion at a rate of 140 micrograms/kg/min for 6 minutes. Two blinded expert observers graded results of adenosine thallium-201 studies as normal (33%), fixed defect only (2%), reversible defect only (48%), and combined (fixed and reversible) defects (17%). After 6 +/- 3 months of follow-up, 81% proceeded to surgery and 43% underwent preoperative coronary angiography. Clinical variables that correlated with perioperative cardiac events were a history of diabetes mellitus (p = 0.05), left bundle branch block (p = 0.02), and left ventricular hypertrophy (p = 0.06) on the resting ECG. This clinically "high-risk" group had an event rate of 22% as compared with no cardiac events in patients in the "low-risk" group without these clinical characteristics (p = 0.005). Stepwise logistic regression analysis revealed that the presence of a combined (fixed and reversible) adenosine thallium-201 defect (p = 0.0007), three-vessel coronary artery disease (p = 0.001), and left bundle branch block (p = 0.02) was predictive of subsequent cardiac events with relative risk ratios of 4.9, 2.9, and 2.2, respectively. Therefore the presence of an adenosine thallium-201 perfusion defect is correlated with and predictive of an increased risk of perioperative cardiac events in patients referred for preoperative risk evaluation.

Prognostic value of dipyridamole thallium-201 imaging in elderly patients.

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)

Application of computerized exercise ECG digitization. Interpretation in large clinical trials.

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.

Prognostic significance of exercise thallium-201 testing in patients aged greater than or equal to 70 years with known or suspected coronary artery disease.

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)

Effects of posture on metabolic and hemodynamic predischarge exercise response after acute myocardial infarction.

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.

Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women.

STUDY OBJECTIVE: To assess the effect of weight-bearing exercise training and subsequent detraining on lumbar bone mineral content in postmenopausal women. DESIGN: Non-randomized, controlled, short-term (9 months) trial and long-term (22 months) exercise training and detraining (13 months). SETTING: Section of applied physiology at a university school of medicine. PATIENTS: Thirty-five healthy, sedentary postmenopausal women, 55 to 70 years old. All women completed the study. There was 90% compliance with exercise training. INTERVENTIONS: All women were given calcium, 1500 mg daily. The exercise group did weight-bearing exercise (walking, jogging, stair climbing) at 70% to 90% of maximal oxygen uptake capacity for 50 to 60 min, 3 times weekly. MEASUREMENTS AND MAIN RESULTS: Bone mineral content increased 5.2% (95% confidence interval [CI], 2.0% to 8.4%; P = 0.0037) above baseline after short-term training whereas there was no change (-1.4%) in the control group. After 22 months of exercise, bone mineral content was 6.1% (95% CI, 3.9% to 8.3% above baseline; P = 0.0001) in the long-term training group. After 13 months of decreased activity, bone mass was 1.1% above baseline in the detraining group. CONCLUSIONS: Weight-bearing exercise led to significant increases above baseline in bone mineral content which were maintained with continued training in older, postmenopausal women. With reduced weight-bearing exercise, bone mass reverted to baseline levels. Further studies are needed to determine the threshold exercise prescription that will produce significant increases in bone mass.