A New 12-Lead ECG Prognostic Score.

BACKGROUND: The Diagonal Line Rule (DLR) is an educational pattern recognition tool for the classification of 12-lead electrocardiograms (ECGs) as normal or abnormal. OBJECTIVE: To develop a score using the DLR for the risk stratification of abnormal ECGs. METHODS: Patients at the Palo Alto, VA, referred for a routine resting ECG between 1987 and 1999 were retrospectively considered. The initial ECGs of 43,798 patients were scored according to the DLR. The main outcome variable was cardiovascular mortality with 8 years of follow-up. RESULTS: ECG abnormalities identified by the DLR were combined with age, gender, and ST depression to develop an additive score. The score was validated and shown to stratify levels of cardiac risk with a 0.78 area under the receiver operating characteristic (ROC) curve for identifying those who had a cardiovascular death. CONCLUSION: The score effectively stratifies ECGs for prediction of risk of cardiovascular death.

Resting ST amplitude: prognosis and normal values in an ambulatory clinical population.

BACKGROUND: There is limited data describing ST segment amplitude in apparently healthy, asymptomatic populations. We analyzed ST amplitude in the standard resting electrocardiogram (ECG) in a large, multiethnic, stable, clinical population. METHODS: We evaluated computerized ST amplitude measurements from the resting ECGs of 29,281 ambulatory outpatients collected between 1987 and 1999 at the Palo Alto, VA. With the PR interval as the isoelectric line, both elevation criteria (≥0.1 mV, ≥0.15 mV, and ≥0.2 mV) and depression criteria (≤-0.05 mV or ≤-0.1 mV), were applied. Cox-Hazard survival analysis techniques were used to demonstrate in which leads ST amplitude displacement was associated with cardiovascular (CV) death. To create a cohort without ECG patterns clearly associated with disease, we excluded ECGs with inverted T waves, wide QRS, or diagnostic Q waves and coded the remaining "normal" ECGs for ST elevation and depression to determine a normal range. RESULTS: The only ST amplitudes that were significantly and independently associated with time to CV death when adjusted for age, gender, and ethnicity were ST depression in all of the lateral leads (I, V4 -V6 ). When isolated to the inferior leads, (II and AVF), no ST amplitude criteria were associated with CV death. Among the "normal ECG" subgroup the precordial leads exhibited the greatest median ST amplitudes and the most significant differences between the leads, genders and ethnicities. CONCLUSIONS: Significant differences in ST amplitude were present in the precordial leads according to gender and ethnicity. This was particularly apparent when amplitude threshold were set for comparisons. Our findings provide the normal range for ST amplitude that when exceeded, should raise clinical concern.

Prognostic value of the computerized ECG in Hispanics.

BACKGROUND: The prevalence and prognostic values of electrocardiogram (ECG) abnormalities in Hispanics have not been compared to other ethnicities in a large population. Despite a worse cardiovascular risk profile, the prevalence of cardiovascular disease is lower in Hispanics compared to non-Hispanics. HYPOTHESIS: We hypothesized that ECG abnormalities were less common in Hispanics and were not as strongly associated with cardiovascular mortality. METHODS: 45,563 ECGs ordered for usual clinical indications in a Veteran's hospital were available for analysis. 1,392 patients who died within one week of the ECG were excluded. Demographic characteristics were recorded and the population was followed for an average of 7.5 years using the California Death Index. The presence of baseline ECG characteristics were recorded and analyzed using the GE/Marquette computerized ECG system. Age, sex and heart rate adjusted Cox hazard ratio analyses were performed. RESULTS: Being Hispanic was associated with lower cardiovascular death, with a hazard ratio (HR) of 0.76 (95% CI 0.65-0.89). Findings such as atrial fibrillation, presence of Q-waves, left ventricular hypertrophy (LVH), upright T-waves in aortic valve replacement (aVR) and cardiac Infarction Injury Scores > 6 were significantly less prevalent in Hispanics than in non-Hispanics. These findings were similarly associated with increased cardiovascular mortality in both groups, each with a HR of approximately 2. CONCLUSION: The lower prevalence of ECG characteristics associated with coronary heart disease, atrial fibrillation and left ventricular hypertrophy support prior observations that cardiovascular disease is less prevalent in the Hispanic population. These findings, however, are similarly associated with increased mortality compared to non-Hispanics.

Homocysteine and hypertension in persons with spinal cord injury.

STUDY DESIGN: Cross-sectional analysis of a convenience sample of locally recruited participants, including both patients and volunteers. OBJECTIVES: To determine whether there is an association between plasma homocysteine and hypertension in persons with spinal cord injury (SCI). SETTING: Spinal Cord Injury Service of the Veterans Affairs Palo Alto Medical Center (California, United States of America). METHODS: The incidence of hypertension, dyslipidemia, insulin resistance, and the presence of metabolic syndrome were determined in 168 individuals with SCI (mean age 50.2 +/- 12.8 years). Fasting lipids, insulin, glucose, plasma homocysteine, and anthropometric data was gathered for each subject. RESULTS: Blood pressure values (P < 0.001) and mean arterial pressure (P < 0.05) increased with higher plasma homocysteine levels. Homocysteine values were also significantly greater among individuals with hypertension compared with those who were normotensive or prehypertensive (P < 0.0001). There was an inverse relationship between plasma homocysteine levels and glomerular filtration rate and effective renal plasma flow (P < 0.05). CONCLUSIONS: Plasma homocysteine levels are elevated in persons with SCI who have hypertension and inversely related to renal function, which suggests that renal dysfunction may be a link between homocysteine and hypertension in persons with SCI. SPONSORSHIP: Funded by the VA Rehabilitation Research and Development Service, Merit Review Grant #B2549R.

Heart rate recovery: validation and methodologic issues.

OBJECTIVES: The goal of this study was to validate the prognostic value of the drop in heart rate (HR) after exercise, compare it to other test responses, evaluate its diagnostic value and clarify some of the methodologic issues surrounding its use. BACKGROUND: Studies have highlighted the value of a new prognostic feature of the treadmill test-rate of recovery of HR after exercise. These studies have had differing as well as controversial results and did not consider diagnostic test characteristics. METHODS: All patients were referred for evaluation of chest pain at two university-affiliated Veterans Affairs Medical Centers who underwent treadmill tests and coronary angiography between 1987 and 1999 as predicted after a mean seven years of follow-up. All-cause mortality was the end point for follow-up, and coronary angiography was the diagnostic gold standard. RESULTS: There were 2,193 male patients who had treadmill tests and coronary angiography. Heart rate recovery at 2 min after exercise outperformed other time points in prediction of death; a decrease of <22 beats/min had a hazard ratio of 2.6 (2.4 to 2.8 95% confidence interval). This new measurement was ranked similarly to traditional variables including age and metabolic equivalents but failed to have diagnostic power for discriminating those who had angiographic disease. CONCLUSIONS: Heart rate at 1 or 2 min of recovery has been validated as a prognostic measurement and should be recorded as part of all treadmill tests. This new measurement does not replace, but is supplemental to, established scores.

Clinical and exercise test predictors of all-cause mortality: results from > 6,000 consecutive referred male patients.

OBJECTIVE: To report the prevalence of abnormal treadmill test responses and their association with mortality in a large consecutive series of patients referred for standard exercise tests, with testing performed and reported in a standardized fashion. BACKGROUND: Exercise testing is widely performed, but few databases exist of large numbers of consecutive tests performed on patients referred for routine clinical purposes using standardized methods. Even fewer of the available databases have information regarding all-cause mortality as an outcome. METHODS: All patients referred for evaluation at two university-affiliated Veterans Affairs medical centers who underwent exercise treadmill testing for clinical indications between 1987 and 2000 were determined to be dead or alive using the Social Security death index after a mean 6.2 years (median, 7 years) of follow-up. Clinical and exercise test variables were collected prospectively according to standard definitions; testing and data management were performed in a standardized fashion using a computer-assisted protocol. All-cause mortality was utilized as the end point for follow-up. Standard survival analysis was performed, including Kaplan-Meier curves and a Cox hazard model. RESULTS: There were 6,213 male patients (mean +/- SD age, 59 +/- 11 years) who underwent standard exercise ECG treadmill testing over the study period with a mean follow-up duration of 6.2 +/- 3.7 years. There were no complications of testing in this clinically referred population, 78% of whom were referred for chest pain, or risk factors or signs or symptoms of ischemic heart disease. Overlapping thirds had typical angina or history of myocardial infarction (MI). Five hundred seventy-nine patients had prior coronary artery bypass surgery, and 522 patients had a history of congestive heart failure (CHF). Indications for testing were in accordance with published guidelines. Twenty percent died over the follow-up period, for an average annual mortality rate of 2.6%. Cox hazard function chose the following variables in rank order as independently and significantly associated with time to death: exercise capacity (metabolic equivalents < 5, age > 65 years, history of CHF, and history of MI. A score based on these variables (summing up the four variables [if yes = 1 point]) classified patients into low-risk, medium-risk, and high-risk groups. The high-risk group (score > or = 3) has a hazard ratio of 5.0 (95% confidence interval, 4.7 to 5.3) and a 5-year mortality rate of 31%. CONCLUSION: This comprehensive analysis provides rates of various abnormal responses that can be expected in patients referred for exercise testing at a typical medical center. Four simple variables combined as a score powerfully stratified patients according to prognosis.

Diagnostic exercise tests on 4000 consecutive men.

OBJECTIVE: Our purpose was to report the prevalence of abnormal treadmill test responses and their association with mortality in a large consecutive series of patients referred for standard diagnostic exercise tests, with testing performed and reported in a standardized fashion. BACKGROUND: Exercise testing is widely performed, but an analysis of responses has not been presented for a large number of consecutive tests performed on patients referred for diagnosis of cardiac disease. METHODS: All patients referred for evaluation at 2 university-affiliated Veterans Affairs Medical Centers who underwent exercise treadmill tests for clinical indications between 1987 and 2000 were determined to be dead or alive according to the Social Security Death Index after a mean 5.9-year follow-up. Patients with established heart disease (ie, prior coronary bypass surgery, myocardial infarction, or congestive heart failure) were excluded from analyses. Clinical and exercise test variables were collected prospectively according to standard definitions; testing and data management were performed in a standardized fashion with a computer-assisted protocol. All-cause mortality was used as the end point for follow-up. Standard survival analysis was performed, including Kaplan-Meier curves and a Cox hazard model. RESULTS: After the exclusions, 3974 men (mean age 57.5 +/- 11 years) had standard diagnostic exercise testing over the study period with a mean of 5.9 (+/-3.7) years of follow-up (64% of all tested). There were no complications of testing in this clinically referred population, 82% of whom were referred for chest pain, risk factors, or signs and symptoms of ischemic heart disease. Five hundred forty-nine (14%) had a history of typical angina. Indications for testing were in accordance with published guidelines. A total of 545 died, yielding an annual mortality rate of 1.8%. The Cox hazard model chose the following variables in rank order as independently associated with time to death: change in rate pressure product, age greater than 65 years, METs less than 5, and electrocardiographic left ventricular hypertrophy. A score based on these variables classified patients into low-, medium-, and high-risk groups. The high-risk group with a score greater than 3 has a hazard ratio of 4 (95% confidence interval 3.82-4.27) and an annual mortality rate of 4%. CONCLUSION: This comprehensive analysis provides rates of various abnormal responses that can be expected in men referred for diagnostic exercise testing at typical Veterans Administration Medical Centers. Four simple variables combined as a score predict all-cause mortality after clinical decisions for therapy are prescribed.

Effects of chronotropic incompetence and beta-blocker use on the exercise treadmill test in men.

OBJECTIVE: Our purpose was to assess the diagnostic characteristics of the exercise test in patients who fail to reach conventional target heart rates and in patients on beta-blockers. BACKGROUND: Exercise test results are often considered "inadequate" or "nondiagnostic" in patients taking beta-blockers and in patients who do not achieve 85% of their age-predicted maximal heart rate. METHODS: The results of exercise tests and coronary angiography performed to evaluate chest pain in 1282 male patients without a prior history of myocardial infarction, coronary revascularization, diagnostic Q wave on the baseline electrocardiogram, or previous cardiac catheterization were analyzed with respect to beta-blocker exposure and failure to reach 85% age-predicted maximal heart rate. Sensitivity, specificity, and predictive accuracy of exercise testing, as well as area under the curve for the receiver operating characteristic plots were calculated for these subgroups with use of coronary angiography as the reference. The angiographic criterion for significant coronary artery disease was 50% narrowing or greater in one or more major coronary arteries. RESULTS: The population was divided into 4 exclusive groups on the basis of whether they reached their target heart rates and whether they were receiving beta-blockers. Sixty to 40 percent of this clinical population failed to reach target heart rate, of which 24% (n = 303) were receiving beta-blockers and 40% (n = 518) were not. The group of patients who reached target heart rate and were not taking beta-blockers was taken as the reference group (n = 409). The group of patients supposedly beta-blocked but who reached the target heart rate (n = 52) had hemodynamic and test characteristics similar to those of the reference group and most likely were not taking their beta-blockers or were not adequately dosed. The prevalence of angiographic coronary disease was significantly higher in the 2 groups failing to reach target heart rate, both in the presence and absence of beta-blockers, compared with the reference group (68% and 64%, respectively, vs 49%, P <.01). Although the areas under the curve of the receiver operating characteristic curves for ST depression of the groups failing to reach target heart rate were not significantly different from the reference group, the predictive accuracy and sensitivity were significantly lower for 1 mm of ST depression in the beta-blocked group who did not reach target heart rate (predictive accuracy of 56% vs 67%, sensitivity of 44% vs 58%, P <.01). The only way to maintain sensitivity with the standard exercise test in the beta-blocker group who failed to reach target heart rate was to use a treadmill score or 0.5-mm ST depression as the criteria for abnormal. CONCLUSION: Sensitivity and predictive accuracy of standard ST criteria for exercise-induced ST depression are significantly decreased in male patients who are taking beta-blockers and do not reach target heart rate. In those who fail to reach target heart rate and are not beta-blocked, sensitivity and predictive accuracy are maintained.

Simple treadmill score to diagnose coronary disease.

OBJECTIVE: Our aim was to derive and validate a simplified treadmill score for predicting the probability of angiographically confirmed coronary artery disease (CAD). BACKGROUND: The American College of Cardiology/American Heart Association guidelines for exercise testing recommend the use of multivariable equations to enhance the diagnostic characteristics of the standard treadmill test. Most of these equations use complicated statistical techniques to provide diagnostic estimates of CAD. Simplified scores derived from such equations that require physicians only to add points have been developed for pretest estimates of disease and for prognosis. However, no simplified score has been developed specifically for the diagnosis of CAD using exercise test results. METHODS: Consecutive patients referred for evaluation of chest pain who underwent standard treadmill testing followed by coronary angiography were studied. A logistic regression model was used to predict clinically significant (> or = 50% stenosis) CAD and then the variables and coefficients were used to derive a simplified score. The simplified score was calculated as follows: (6 x maximal heart rate code) + (5 x ST-segment depression code) + (4 x age code) + angina pectoris code + hypercholesterolemia code + diabetes code + treadmill angina index code. The simplified score had a range from 6 to 95, with < 40 designated as low probability, between 40 and 60 was intermediate probability, and > 60 was high probability for CAD. RESULTS: A total of 1,282 male patients without a prior myocardial infarction underwent exercise treadmill testing and coronary angiography in the derivation group, and there were 476 male patients in the validation group from another institution. The area under the receiver operating characteristic curve (+/- SE) for the ST-segment response alone was 0.67 as compared to 0.79 +/- 0.01 for the diagnostic score (p > 0.001). The prevalence of significant disease for the men was 27% in the low-probability group, 62% in the intermediate-probability group, and 92% in the high-probability group, which was similar to the prevalence in the validation group, with 22%, 58%, and 92% in low-, intermediate-, and high-probability groups, respectively. The low-probability group had < 4% prevalence of severe disease. In both populations, 7 more patients out of 100 were correctly classified than with the use of ST-segment criteria. When used as a clinical management strategy, the score has a sensitivity of 88% and a specificity of 96%. CONCLUSION: This simplified exercise score that estimates the probability of CAD can be easily applied without a calculator and is a useful and valid tool that can help physicians manage patients presenting with chest pain.

Clinical utility of the exercise ECG in patients with diabetes and chest pain.

OBJECTIVE: The purpose of this study was to determine the characteristics of exercise treadmill testing in diabetic patients presenting with chest pain. BACKGROUND: The diagnosis of coronary artery disease (CAD) in diabetic patients is confounded by different manifestations of coronary disease than are seen in the general population. Because of the association of diabetes with accelerated CAD, it is critical to assess the diagnostic utility of the standard exercise test in diabetic patients with chest pain. METHODS: This study was a retrospective analysis of standard exercise test results in 1,282 male patients without prior myocardial infarction who had undergone coronary angiography and were being evaluated for possible CAD at two Veterans' Administration institutions. RESULTS: In patients with diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 69%; the sensitivity of the exercise test was 47% (95% confidence interval [CI], 41 to 58), and specificity was 81% (95% CI, 68 to 89). In patients without diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 58%; the sensitivity of the exercise test was 52% (95% CI, 48 to 56), and specificity was 80% (95% CI, 76 to 83). The receiver operating characteristic curves were also similar in both diabetic and nondiabetic patients (0.67 and 0.68, respectively). CONCLUSION: These data demonstrate that the standard exercise test has similar diagnostic characteristics in diabetic as in nondiabetic patients.

Exercise testing in the new millennium.

In the changing economic times, internists and family physicians are becoming the main performers of the standard exercise test. The education of those noncardiologists who wish to perform exercise testing is quite important. In the new millennium, the American College of Cardiology/American Heart Association evidence-based guidelines on exercise testing continue to have a large impact. Used for diagnosis or prognosis, exercise scores such as the Duke exercise score will be applied to each test. Increased computerization and the internet will bring inexpensive web-enabled devices for sophisticated exercise testing into the doctor's office and allow remote over-reading services.

Computer applications in the interpretation of the exercise electrocardiogram.

The exercise electrocardiogram remains the noninvasive diagnostic test of first choice in patients with coronary artery disease. While new technology offers novel diagnostic possibilities and the ability to assess patients unsuitable for exercise testing, no other investigation has to this point furnished the quality of functional information and value-for-predictive accuracy of exercise electrocardiography. In this article, we describe how this central position in the work up of the cardiac patient has been secured through the evolution of the microprocessor. Particularly important has been its ability to harness and present large volumes of raw data, to derive and manipulate multivariate equations for diagnostic prediction, and to run 'expert' systems which can pool demographic and exercise test data, calculate risk scores, and prompt the nonexpert with advice on current management. These key features explain the pivotal role of the exercise test in the diagnostic, and increasingly prognostic, armoury of the cardiovascular clinician.

A survey of exercise testing: methods, utilization, interpretation, and safety in the VAHCS.

BACKGROUND: Healthcare organizations are being graded in terms of their adherence to practice guidelines. The authors sought information on practice patterns of exercise testing within the Veterans Affairs Health Care System (VAHCS) to determine how well current practice patterns adhere to current guidelines. In addition, we sought to update past surveys to determine methods, indications, utilization of alternative diagnostic modalities, criteria for interpretation, safety, and physician supervision of exercise testing within the VAHCS. METHODS: Questionnaires were sent to 72 of the largest Veterans Affairs Medical Centers with cardiology divisions. The centers were queried regarding volume and type of exercise testing (standard, nuclear, and echocardiographic), indications, safety, protocols used, and criteria for interpretation. RESULTS: Seventy-one questionnaires were returned, comprising a total of 75,828 exercise tests performed within the last year. Virtually all indications for exercise testing fit the American Heart Association/American College of Cardiology (AHA/ACC) guidelines Class I criteria; 46% of patients were tested for the evaluation of chest pain; 14% were tested to evaluate patients at high risk for coronary artery disease; 10% were preoperative evaluations; and 8% were post-myocardial infarction evaluations. The most commonly used diagnostic test was the standard exercise electrocardiogram; a patient was five times more likely to undergo a standard exercise electrocardiogram or nuclear exercise test than an exercise or pharmacologic echocardiogram. The largest proportion of centers (49%) used 1.0-mm horizontal or downsloping ST depression as a criterion for an abnormal test, although 22% considered 1.5-mm upsloping ST depression to be abnormal, and 25% relied on a treadmill score. Seventy-eight percent of respondents used the treadmill, and of these, 82% used the Bruce or modified Bruce protocol. Four major cardiac events were reported (three myocardial infarctions, one sustained ventricular tachycardia) representing an event rate of 1.2/10,000. A physician was present during 73% of all standard exercise tests; 21% of respondents reported that a physician was required to be present "only for high-risk patients." CONCLUSION: Indications for exercise testing are in close agreement with the AHA/ACC guidelines; thus, the test continues to have an important role in diagnosis and prognosis among patients with or suspected of having coronary artery disease. The exercise test is an extremely safe procedure, with an event rate similar to other recent surveys. However, a great deal of variation exists in terms of criteria for abnormal results and whether physician presence is required during exercise testing.

The effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test.

OBJECTIVES: The aim of this study is to demonstrate the effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test. BACKGROUND: Previous studies evaluating the effect of resting ST segment depression on the diagnostic characteristics of exercise treadmill test have been conducted on relatively small patient groups and based only on visual electrocardiogram (ECG) analysis. METHODS: A retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. One thousand two hundred eighty-two patients without a prior myocardial infarction underwent standard exercise treadmill tests followed by coronary angiography, with coronary artery disease defined as a 50% narrowing in at least one major epicardial coronary artery. Sensitivity, specificity, predictive accuracy and area under the curve of the receiver operating characteristic (ROC) plots were calculated for patients with and without resting ST segment depression as determined by visual or computerized analysis of the baseline ECG. RESULTS: Sensitivity of the exercise treadmill test increased in 206 patients with resting ST segment depression determined by visual ECG analysis compared with patients without resting ST segment depression (77 +/- 7% vs. 45 +/- 4%) and specificity decreased (48 +/- 12% vs. 84 +/- 3%). With computerized analysis, sensitivity of the treadmill test increased in 349 patients with resting ST segment depression compared with patients without resting ST segment depression (71 +/- 6% vs. 42 +/- 4%) and specificity decreased (52 +/- 9% vs. 87 +/- 3%) (p < 0.0001 for all comparisons). There was no significant difference in the area under the curve of the ROC plots (0.66-0.69) or the predictive accuracy (62-68%) between the four subgroups. CONCLUSIONS: The diagnostic accuracy and high sensitivity of the exercise treadmill test in a large cohort of patients with resting ST segment depression and no prior myocardial infarction support the initial use of the test for diagnosis of coronary artery disease. The classification of resting ST segment depression by method of analysis (visual vs. computerized) did not affect the results.

Does elevated cardiac troponin I in patients with unstable angina predict ischemia on stress testing?

To help guide physicians in their evaluation of patients with acute coronary syndromes, we investigated whether elevated cardiac troponin I in patients presenting with unstable angina predicts ischemia on stress testing. Elevated cardiac troponin I in patients who present with chest pain and normal creatine kinase levels is associated with ischemia on stress testing, as well as with future cardiac events.