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.

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.

Management of the patient with congestive heart failure using outpatient, home, and palliative care.

Congestive heart failure is a chronic, debilitating illness, with increasing prevalence in the elderly. It is one of the most common causes for hospital admission, and associated treatment costs are estimated at $20.2 billion. Despite improved survival with medical therapy, beneficial effects on quality of life have not been consistently reported. In addition, optimum medical therapy, as recommended by evidence-based guidelines, are not always implemented. Counseling and education involving dietary modifications, activity recommendations, medication management, self-monitoring, prognosis, coping skills, social support, caregiver stress, and spiritual needs are critical components in the management of heart failure through initial diagnosis to end of life. Within the last decade, close follow-up for congestive heart failure has been associated with decreased hospitalizations, reduced hospital length of stay, improved functional status, better compliance, lower costs, and improved survival. Research trials have mainly been observational and small, and they have used different interventions. Little has been written regarding outpatient management of the patient with advanced congestive heart failure, and none of the current published guidelines addresses recommendations for the New York Heart Association class IV (other than for transplant candidacy). New models of close follow-up for chronic and advanced congestive heart failure should be investigated. These models could be implemented in urban and rural settings and be supported by private insurance or Medicare.

Effect of betaxolol on the hemodynamic, gas exchange, and cardiac output response to exercise in chronic atrial fibrillation.

BACKGROUND: beta-blockade controls the ventricular response to exercise in chronic atrial fibrillation (AF), but the effects of beta-blockers on exercise capacity in AF have been debated. METHODS: Twelve men with AF (65+/-8 years) participated in a randomized, double-blind, placebo-controlled study of betaxolol (20 mg daily). Patients underwent maximal exercise testing with ventilatory gas exchange analysis, and a separate, submaximal test (50% of maximum) during which cardiac output was measured by a CO2 rebreathing technique. RESULTS: After betaxolol therapy, heart rate was reduced both at rest (92+/-27 vs 62+/-12 beats/min; p < 0.001) and at peak exercise (173+/-22 vs 116+/-24 beats/min; p < 0.001). Maximal oxygen uptake (VO2) was reduced by 19% after betaxolol (21.8+/-5.3 with placebo vs 17.6+/-5.1 mL/kg/min with betaxolol; p < 0.05), with similar reductions observed for maximal exercise time, minute ventilation, and CO2 production. VO2 was reduced by a similar extent (19%) at the ventilatory threshold. Submaximal cardiac output was reduced by 15% during betaxolol therapy (12.9+/-2.3 vs 10.9+/-1.3 L/min; p < 0.05), and stroke volume was higher (88.0+/-21 vs 105.6+/-19 mL/beat; p < 0.05). CONCLUSION: Betaxolol therapy in patients with AF effectively controlled the ventricular rate at rest and during exercise, but also caused considerable reductions in maximal VO2 and cardiac output during exercise. The observed increase in stroke volume could not adequately compensate for reduced heart rate to maintain VO2 during exercise.

Predicting severe angiographic coronary artery disease using computerization of clinical and exercise test data.

Currently the standard exercise test is shifting from being a tool for the cardiologist to utilization by the nonspecialist. This change could be facilitated by computerization similar to the interpretation programs available for the resting ECG. Therefore, we sought to determine if computerization of both exercise ECG measurements and prediction equations can substitute for visual analysis performed by cardiologists to predict which patients have severe angiographic coronary artery disease. We performed a retrospective analysis of consecutive patients referred for evaluation of possible or known coronary artery disease who underwent both exercise testing with digital recording of their exercise ECGs and coronary angiography at two university-affiliated Veteran's Affairs medical centers and a Hungarian hospital. There were 2,385 consecutive male patients with complete data who had exercise tests between 1987 and 1997. Measurements included clinical and exercise test data, and visual interpretation of the ECG paper tracings and > 100 computed measurements from the digitized ECG recordings and compilation of angiographic data from clinical reports. The computer measurements had similar diagnostic power compared with visual interpretation. Computerized ECG measurements from maximal exercise or recovery were equivalent or superior to all other measurements. Prediction equations applied by computer were only able to correctly classify two or three more patients out of 100 tested than ECG measurements alone. beta-Blockers had no effect on test characteristics while ST depression on the resting ECG decreased specificity. By setting probability limits using the scores from the equations, the population was divided into high-, intermediate-, and low-probability groups. A strategy using further testing in the intermediate group resulted in 86% sensitivity and 85% specificity for identifying patients with severe coronary disease. We conclude that computerized exercise ST measurements are comparable to visual ST measurements by a cardiologist and computerized scores only minimally improved the discriminatory power of the test. However, using these scores in a stratification algorithm allows the nonspecialist physician to improve the discriminatory characteristics of the standard exercise test even when resting ST depression is present. Computerization permitted accurate identification of patients with severe coronary disease who require referral.

Can computerization of the exercise test replace the cardiologist?

BACKGROUND: The type of practitioners who use the standard exercise test is changing. Once a tool of the cardiologist, the standard exercise test is now being performed by internists and other noncardiologists. Because this change could be facilitated by computerization similar to the computerized interpretation programs available for the resting electrocardiograph (ECG), we performed this analysis. A secondary aim was to demonstrate the effects of medication status and resting ECG abnormalities on test diagnostic characteristics because these factors affect utility of the exercise test by the generalist. METHODS AND RESULTS: A retrospective analysis was performed of consecutive patients referred at 2 university-affiliated Veteran's Affairs Medical Centers and a Hungarian Hospital for evaluation of chest pain and possible ischemic heart disease. There were 1384 consecutive male patients without a prior myocardial infarction with complete data who had exercise tests and coronary angiography between 1987 and 1997. Measurements included clinical, exercise test data, and visual interpretation of the ECG recordings as well as more than 100 computed measurements from the digitized ECG recordings and compilation of angiographic data from clinical reports. The computer measurements had similar diagnostic power compared with visual interpretation. Computerized measurements from maximal exercise or recovery were equivalent or superior to all other measurements. Prediction equations applied by computer were superior to single ECG measurements. Beta-blockers had no effect on test characteristics, whereas resting ST depression was associated with decreased specificity and increased sensitivity. CONCLUSIONS: Computerized exercise ST measurements are comparable to visual ST measurements by a cardiologist; computerized scores that included clinical and exercise test results exhibited the greatest diagnostic power. Applying scores with a computer allows the practicing physician to improve the diagnostic characteristics of the standard exercise test. This approach is successful even when there is resting ST depression, thus lessening the need for more expensive nuclear or imaging studies.

An agreement approach to predict severe angiographic coronary artery disease with clinical and exercise test data.

OBJECTIVE: To demonstrate that an agreement approach to applying equations on the basis of clinical and exercise test variables is an accurate, self-calibrating, and cost-efficient method for predicting severe coronary artery disease in clinical populations. DESIGN: Retrospective analysis of consecutive patients with complete data from exercise testing and coronary angiography referred for evaluation of possible coronary artery disease. After developing an equation in a training set, this equation and two other equations developed by other investigators were validated in a test set. The study was performed at two university-affiliated Veteran's Affairs medical centers. PATIENTS: 1080 consecutive men studied between 1985 and 1995 who had coronary angiography within 3 months of the treadmill test. The population was randomly divided into a training set of 701 patients and a test set of 379 patients. Patients with previous coronary artery bypass surgery, valvular heart disease, marked degrees of resting ST depression, and left bundle branch block were excluded. MEASUREMENTS: Recording of clinical and exercise test data along with visual interpretation of the electrocardiogram recordings on standardized forms and abstraction of visually interpreted angiographic data from clinical catheterization reports. RESULTS: Simple clinical and exercise test variables improved the standard application of exercise-induced ST criteria for predicting severe coronary artery disease. By setting probability thresholds for severe disease of <20% and >40% for the three prediction equations, the agreement approach divided the test set into three groups: low risk (patients with all three equations predicting <21% probability of severe coronary disease), no agreement, and high risk (all three equations with >39% probability) for severe coronary artery disease. Because the patients in the no agreement group would be sent for further testing and would eventually be correctly classified, the sensitivity of the agreement approach was 89% and the specificity was 96%. The agreement approach appeared to be unaffected by disease prevalence, missing data, variable definitions, or even angiographic criteria. CONCLUSIONS: Requiring diagnosis of severe coronary disease to be dependent on agreement between these three equations has made them likely to function in all clinical populations. The agreement approach should be an efficient method for the evaluation of populations with varying prevalence of coronary artery disease, limiting the use of more expensive noninvasive and invasive testing to patients with a higher probability of left main or triple-vessel coronary artery disease. This approach provides a strategy that can be applied by inputting the results of basic clinical assessment into a programmable calculator or a computer to assist the practitioner in deciding when further evaluation is appropriate, thus assuring patients access to subspecialty care.

Review of studies using multivariable analysis of clinical and exercise test data to predict angiographic coronary artery disease.

Multivariable analysis of clinical and exercise test variables has the potential to become both a useful tool for assisting in the diagnosis of coronary artery disease and reducing the cost of evaluating patients with suspected coronary disease. Managed care and capitation require that tests such as the exercise test or its replacements, be used only when they can accurately and reliably identify which patients need medications, counseling, or further evaluation or intervention. The replacements for the standard exercise electrocardiogram test require expensive equipment and personnel, and their incremental value is currently being evaluated. Because general practitioners are to function as gatekeepers and decide which patients must be referred to the cardiologist, they will need to use the basic tools they have available (ie, history, physical exam, and the exercise test) in an optimal fashion. However, the discriminating power of the variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. There is a need for further evaluation of these routinely obtained variables to improve the accuracy of prediction algorithms especially in women. Of paramount concern is the need to avoid workup bias by having patients agree to testing before the decision for angiography is made. The portability and reliability of these equations must be shown because access to specialized care must be safeguarded. By reviewing the available studies considering clinical and exercise test variables to predict coronary angiographic findings, we have attempted to provide guidelines and recommendations for a more uniform approach to this endeavor in future investigations. Hopefully, the next generation of multivariable equations will be robust and portable, and empower the clinician to assure the cardiac patient access to appropriate cardiac care.

Variability of normal coronary anatomy: implications for the interpretation of thallium-SPECT myocardial perfusion images in single-vessel disease.

UNLABELLED: Standard criteria for assigning perfusion defects to a specific vascular territory often result in mistaken identification of the affected coronary artery due to the normal variability of coronary anatomy. A retrospective study was performed to determine the frequency of this type of error and to identify the most common perfusion patterns associated with specific coronary lesions. METHODS: Records were reviewed of all patients with single-vessel coronary artery disease (CAD) who had exercise or dipyridamole thallium SPECT myocardial perfusion studies since 1987. Patients with coronary artery bypass grafts and an interval between the two studies greater than 6 wk or interval change in medical status were excluded. Ninety-three studies were available for review. The size, severity and location of all perfusion defects were noted by three observers who had no knowledge of the angiographic data. Significant CAD was defined as luminal diameter stenosis greater than 50%. RESULTS: The diseased vessel was correctly identified in 85% of positive studies. Thallium SPECT, however, mistakenly predicted additional vessel involvement in 29% of those studies. Another 15% correctly predicted single-vessel disease but identified the wrong artery. Using standard criteria, thallium SPECT correctly predicted the arteriogram findings in only 56% of studies. Most of these findings could be correlated with variations in individual coronary anatomy. CONCLUSION: The accurate localization of coronary stenoses by thallium SPECT imaging requires close correlation with arteriography owing to the significant variability in normal coronary anatomy.

Comparison of thallium-201 single-photon emission computed tomographic scintigraphy with intravenous dipyridamole and arm exercise.

In patients who cannot perform treadmill exercise, both intravenous dipyridamole and arm exercise have been used with thallium-201 scintigraphy to detect significant coronary artery disease. However, no study has directly evaluated the results of intravenous dipyridamole and arm exercise thallium scintigraphy as compared with coronary angiography. It was the purpose of this study to compare intravenous dipyridamole and arm exercise thallium-201 single-photon emission computed tomographic (SPECT) scintigraphy for detection of significant coronary artery disease in patients who could not perform treadmill exercise. Data are presented for both intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy in 18 men who could not perform treadmill exercise, and results are compared with those of coronary angiography. Ten of 11 (91%) patients with significant coronary artery disease were identified correctly, and the results of intravenous dipyridamole and arm exercise thallium scintigraphy were comparable. In patients without significant coronary artery disease, intravenous dipyridamole thallium images were interpreted correctly. However, initial arm exercise thallium images demonstrated a fixed inferior wall defect in two of seven patients without significant coronary artery disease. Images in one of these patients could not be retrieved from tape for further analysis. Review of the images in the other patient demonstrated relatively high background radioactivity, and when the images were displayed without background subtraction, the inferior wall was correctly interpreted as normal. We conclude that results of intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy are comparable.

Transesophageal echocardiographic findings in stroke subtypes.

BACKGROUND AND PURPOSE: Transesophageal echocardiography has a high yield for detecting potential cardiac sources of embolism in patients with clinical risk factors for cardioembolism or unexplained stroke. The yield in other stroke subtypes is unknown. METHODS: We classified 145 consecutively admitted patients into stroke subtypes based on clinical findings, brain imaging, and carotid ultrasound. Both transesophageal and transthoracic echocardiography were performed to detect left atrial thrombi, spontaneous echo contrast, atrial septal aneurysm, interatrial shunts, ventricular thrombus or aneurysm, and myxomatous mitral valve. RESULTS: Transesophageal echocardiography documented at least one of these findings in 46% of the patients compared with an 8% yield on the transthoracic study (P = .002). The yield of transesophageal echocardiography was substantial in all stroke subgroups. Patients with clinical risk factors for cardiac embolism had the highest frequency of spontaneous echo contrast (P = .001). Atrial septal aneurysms were most frequent in patients with lacunar syndromes (P = .012), and interatrial shunts were common in all stroke subtypes. CONCLUSIONS: Transesophageal echocardiographic findings vary considerably between stroke subgroups.

Viability and biodistribution of 68Ga MPO-labelled human platelets.

The viability and biodistribution of 68Ga-mercaptopyridine-N-oxide (MPO)-labelled autologous platelets was studied in 10 patients. The average platelet labelling yield was 36 +/- 12% and injected activity was 2.0 +/- 0.9 mCi 68Ga. The % activity in platelets per ml whole blood was 64 +/- 20% at 15 min-1.0 h postinjection and 76 +/- 14% at 2-4h. The average recovery of platelets (% injected platelets circulating in peripheral blood) was 31 +/- 21% at 15 min-1 h and 39 +/- 20% at 2-4 h. The positron emission tomographic (PET) images showed high circulating vascular background. Two patients had technically inadequate scans, and six were false negative due to high blood background. One patient with a massive pulmonary embolus occurring 24 h prior to scanning had marked uptake of 68Ga platelets in a large clot in the superior branch of the right main pulmonary artery. A second patient, with 68Ga platelets circulating during angioplasty of a left posterior tibial artery stenosis, had intense uptake in the lesion shown on the PET scan obtained 4 h following the procedure. These results indicate good viability of 68Ga-MPO-labelled autologous human platelets, but poor visualization of clots by PET imaging, due to the high blood background at early times.