STRESS & CARDIOVASCULAR DISEASE.
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Research proposal to measure reliability of stress tests in screening for heart problems.... More...
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Research proposal to measure reliability of stress tests in screening for heart problems.
EXERCISE STRESS TESTS AS INDICATORS OF CARDIOVASCULAR DISEASE: A RESEARCH PROPOSAL Introduction Statement of the Problem The issue of whether exercise stress testing should be used to screen asymptomatic men has prompted considerable debate (Evans & Karunaratne, 1992, pp. 121-132). An analysis using a cost/benefit model found little additional benefit from screening asymptomatic patients at average risk of cardiovascular disease. Many of the assumptions in this analysis can be criticized, and the case for or against the use of exercise stress testing in high-risk patients was not separately analyzed. Alternative opinion holds that stress testing is useful in screening asymptomatic men with multiple coronary risk factors, although
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Previtali, M., Lanzarini, L., Fetiveau, R., Poli, A., Ferrario, M.,Falcone, C., & Mussini, A. 121-132). To compare the value of dobutamine and dipyridamole stressechocardiography with exercise stress testing for the diagnosis of coronaryartery disease (CAD), 8 patients with chest pain of suspected myocardialischemic origin (57 with CAD and 23 without significant CAD) underwentdobutamine stress echocardiography (5 to 4 [mu]g/kg/min), dipyridamoleechocardiography ( .84 mg/kg over 1 minutes) and bicycle exerciseelectrocardiography after discontinuation of antianginal treatment(Previtali, Lanzarini, Fetiveau, Poli, Ferrario, Falcone, & Mussini, 1993,pp. Stress echocardiographyprovides direct information regarding myocardial systolic function withstress and enables the direct detection of myocardial ischemia.Significant coronary arterial narrowings are accurately detected. One MET is equal to 3.5 mL ofoxygen per kg per minute, the basal metabolic rate. Use of thesevariables may help reduce the false-positive rate of exercise stresstesting in women with chest pain. EXERCISE STRESS TESTS AS INDICATORS OF CARDIOVASCULAR DISEASE: A RESEARCH PROPOSAL IntroductionStatement of the Problem The issue of whether exercise stress testing should be used to screenasymptomatic men has prompted considerable debate (Evans & Karunaratne,1992, pp. 679-688). Fourteen patients were tested on a treadmill withmonitoring of heart rate, breathing, and blood pressure. Exercise stress tests tend to produce false-positive outcomes inapparently healthy subjects. Ancillary information regarding cardiac blood flow and functioncan also be obtained using nuclear medicine techniques (such as thallium-2 1 scintigraphy, radionuclide angiography and positron emissiontomography), but they are more expensive and time-consuming than is stressechocardiography, and they expose the patient to radioactivity. 679-688). Anelevation of more than 1 mm Hg in the diastolic pressure during exerciseis abnormal and should be considered a hypertensive response to exercise. A study was conducted to determine if exercise testing may uncoverindications of abnormal responses in asymptomatic patients with valvularaortic stenosis (Clyne, Arrighi, Maron, Dilsizian, Bonow, & Cannon, 1991,pp. This difference becomes smaller when women reach 5 years ofage. A muchbetter use of exercise stress testing is to determine the patient's pre-test likelihood of coronary artery disease and then use the results of thetreadmill test to determine a new post-test likelihood. A., Vilacosta, I., Castillo, J. At the end of the EST,data will be collected and recorded. S., Gerber, R. These independent variables are the absence ofmitral valve prolapse, an exercise time of less than five minutes, reachingthe target heart rate and prolonged duration of stress test (ST)-segmentdepression for at least six minutes during recovery. Each stage is defined by the grade and speedof the treadmill. Each stage usuallylasts three minutes, with enough time for the patient to adjust to the newlevel of exercise and enough time for evaluation of the hemodynamicresponse. If a 1-mm ST-segment depression isoberved during the test, the post-test likelihood of significant coronaryartery disease is about 97 percent. Similarly, the filling rate early in the heart cycle wasreduced among the patients with valvular aortic stenosis. Study results found that dobutamine-atropine and dipyridamoleechocardiography have a similar sensitivity and a higher specificity thanthat obtained by exercise ECG for the diagnosis of coronary artery disease. (1992, February). American Family Physician, 45(2), 679-688. 679-688). This fraction, known as the left ventricular ejection fraction,averaged 65 percent for the patients with valve disease and 58 percent forthe controls. M., Francis, M. Thefalse-positive rate, thus, is 1 percent to 2 percent in such cases. Further,stress echocardiography can be used in the large group of patients withknown coronary artery disease (based on symptoms, prior myocardialinfarction, coronary artery bypass surgery [CABG] and coronaryarteriography) to determine current evidence of exercise-induced myocardialischemia. The researchers recommended that pharmacologic stressechocardiography should be used as a first-step test to rule out coronaryartery disease in patients not capable of exercising. Overall, stress testing has a sensitivity and a specificity ofabout 7 percent and 75 percent, respectively, but the results are evenmore useful than this considered within the context of the pre- and post-test probability of coronary artery disease. B. Analysis of variance (ANOVA)procedures will be used to perform the comparison of the two data sets. American Journal of Cardiology, 68(15), 1469-1476. 1469-1476). 679-688). In the tests that yielded positive results,double product during exercise was significantly higher than that duringdobutamine and dipyridamole echocardiography. Thediastolic pressure usually remains at baseline levels or decreases. For example, testing is performed in a 4 -year-old asymptomaticman whose pre-test likelihood of coronary artery disease is about 4percent. Even in women with chest painsuggesting angina, the false-positive rate ranges from 25 percent to 5 percent. If a 1. The proposed research study will test the hypothesis that the use ofTMI in conjunction with EST will reduce the frequency of false-positiveoutcome produced by EST in apparently healthy male subjects to less than 2 percent.Delimitations Female subjects will not be included in the proposed study. Unfortunately, the predicted maximal heartrate varies considerably from person to person (standard deviation of [+ or-] 12 beats per minute). Radionuclide studies allow evaluation of either the myocardium(thallium imaging) or the endocardial blood pool (first-pass or gatedequilibrium radioangiography) during graded exercise testing (Evans &Karunaratne, 1992, pp. 5, respectively).Diagnostic accuracy of dobutamine echocardiography was higher than that ofexercise (8 va 67%, p < . In this group, most positive tests are actually falsepositive. Certain ST-segment patterns correlate with various degrees ofischemia. Thus, dobutamine echocardiography may be superior todipyridamole echocardiography and exercise electrocardiography for thediagnosis of CAD. (1996, November).Dipyridamole and dobutamine-atropine stress echocardiography in thediagnosis of coronary artery disease: comparison with exercise stress test,analysis of agreement, and impact of antianginal treatment. Therefore, that testresults must be valid. As treadmill work increases, systolic bloodpressure increases and reaches a maximum at peak exercise levels. A hypertensive response to stress might contribute to the clinician'sdecision to treat a patient with labile hypertension, or to increase themedication in a patient who is already receiving treatment. These imaging techniques increase thesensitivity and specificity of stress testing and allow evaluation ofmyocardial perfusion, wall motion and ejection fraction. Similar information is obtained with dipyridamole and dobutamine-atropineechocardiography. Grosse, H. (1994, 15 May). American Journal of Cardiology, 71(8), 1469-1476. An example is a 5 -year-old man being tested for atypical chest pain.Before testing, the pre-test likelihood of significant coronary arterydisease is 2 percent. Exercise stress testing is not helpful in evaluating patients with alow pre-test probability of coronary artery disease (Evans & Karunaratne,1992, pp. The criterion for the rejection of thenull will be p<. Alternative opinionholds that stress testing is useful in screening asymptomatic men withmultiple coronary risk factors, although this issue still debated. Bycontrast the false-positive outcome frequency from EST for apparentlyhealthy women is 8 .5 percent.Hypotheses Thallium myocardial imaging (TMI) used in conjunction with exercisestress testing (EST) may improve the diagnostic and prognostic accuracy ofEST. The positive treadmill test addedlittle additional diagnostic information. Unfortunately,these imaging techniques greatly increase the expense of the procedure($1, to $1,4 ). Prognostic usefulness of positive or negative exercisestress echocardiography for predicting coronary events in ensuing twelvemonths. (1991, 1 December). The EST data will serve as the pre-test data, while theTMI data will serve as the post-test data. A., Arrighi, J. If the test had shown no ST-segment depression (a negative test), the post-test likelihood of diseasewould still be 6 percent. Valvular aortic stenosis may occur, however, without symptoms.Evaluating such patients on the basis of exercise testing may be possible.Such evaluation may permit making informed decisions about the best form ofmanagement for individual cases. 679-688). Anexercise stress test, however, should not be considered thissimplistically, because sensitivity and specificity are dependent on theprevalence of coronary artery disease in the population tested. Pratt, C. Because of the cost of radionuclide studies, regularstress testing remains an acceptable screening study. If the test is negative, the probability drops to 8percent. The blood pressure response to exercise among thevalvular aortic stenosis patients reached a systolic pressure of 177millimeters of mercury (mm of Hg), in contrast with 214 mm of Hg for thecontrol subjects. The maximal heart rate, however, decreases with age.The exercise report should state the maximal heart rate achieved as apercentage of the predicted maximal heart rate. In a 6 -year-old man with typical angina, the pre-test likelihood ofcoronary artery disease is 92 percent. W., & Huber, T. Many of the assumptions in this analysis can becriticized, and the case for or against the use of exercise stress testingin high-risk patients was not separately analyzed. The false-positive outcome frequency from EST for apparentlyhealthy men is 36.4 percent (Grosse & Huber, 1994, pp. For this reason, most cardiologists exercise patients to a maximaleffort (maximal exercise test) or until symptoms occur (symptom-limitedtest).Design and Analysis EST and TMI data for all subjects will be analyzed to determine thefrequency of positive test outcomes in each group. Subjects will be selected through the use of randomprocedures.Instrumentation Standard instrumentation will not be used in the proposed study.Rather, cardiographic data will be collected and recorded for each subjectat two points. Theliterature indicates that including female subjects in a test of EST may beimprudent because of the very high false-positive test outcome frequency.Definitions of Terms Exercise stress testing (ST) is a tool to identify patients withcoronary artery disease (Evans & Karunaratne, 1992, pp. 1248-1254). The heart rate and blood pressure response are best analyzed bycomparing them with normal values. 139-144) identified fourindependent variables that predict the presence of coronary artery diseasein women with chest pain and positive results on exercise stress testingusing the Bruce protocol. Systemic and left ventricularresponses to exercise stress in asymptomatic patients with valvular aorticstenosis. Exercisestress testing helps the family physician decide which patients needreferral for catherization.Assumptions Information gained from exercise stress testing (ST) includes theheart rate and blood pressure response, the presence of symptoms ordysrhythmias, functional aerobic capacity and evidence of myocardialischemia. Valvular aortic stenosis, or narrowing of the path through the aorticvalve, can result in difficulty breathing, chest pain, and alterations inconsciousness (Clyne, Arrighi, Maron, Dilsizian, Bonow, & Cannon, 1991, pp.1469-1476). Dobutamine and dipyridamole showed a higher specificitythan exercise (83 vs 43%, p < . S., Lem, V., & Moser, D.(1993, 15 March). W., & Young, J. 679-688). H., & Karunaratne, H. If ST-segment depression of more than 2.5 mm is observed, theprobability of disease increases to 7 percent, but this degree of ST-segment depression is unusual in this setting. All subjects then will complete aTMI. J., Divine, G. References Clyne, C. Asubmaximal test is terminated after a target heart rate has been achieved.The target heart rate is usually 85 percent of the predicted maximal heartrate based on standard graphs. 1; 96 vs 43%, p < . (1993, 15 October). The work is expressed in metabolic equivalents (METS),multiples of the basal metabolic rate. If the test shows 2-mm ST-segment depression, the probabilityincreases to 75 percent. 679-688). 5, respectively). O., III. A research study was conducted to compare the usefulness ofdipryridamole, echocardiography, dobutamine-atropine echocardiography andexercise stress testing in the diagnosis of coronary artery disease and toanalyze the agreement among the tests (San Roman, Villacosta, Castillo,Rollan, Peral, Sanchez-Harguidey, & Fernandez-Aviles, 1996, pp. San Roman, J. 121-132). American Journalof Cardiology, 72(12), 865-87 . MethodSubjects A total of 1 adult male subjects (age range 35 to 55) will beselected from among a population of such subjects who have been determinedto be free of CAD. Chest, 11 (5),1248-1254. B. Patients with anegative treadmill test have a low likelihood of future myocardial ischemicevents (Evans & Karunaratne, 1992, pp. (1992, January). The best measurement ofpeak heart rate is made during a 1 -second monitor strip just before thetermination of testing. Radioactive isotopes were used to measure the filling of the heartwith blood and the pumping of this blood. Literature Review The increase in heart rate that occurs during aerobic exercisecorrelates linearly with workload and oxygen uptake (Evans & Karunaratne,1992, pp. Healthypeople experience an increase in blood pressure in response to exercise.This increase was smaller in magnitude among the patients with valvularaortic stenosis. 233-239). A major difference between the analysis of variance procedure andregression analysis is that, in analysis of variance, the emphasis is onanalysis of the variations in the independent variable, as opposed to thejoint interaction of the variations in dependent and independent variables. B. American Family Physician, 45(1), 121-132. J.,Peral, V., Sanchez-Harguidey, L., & Fernandez-Aviles, F. One result of this difference in emphasis is that, in regression analysis,both the independent and the dependent variables must be measured on aninterval scale, whereas, in analysis of variance procedures, only thedependent variable is required to be measured on an interval scale.Correlation analysis is a derivation of regression analysis. A drop in the systolic blood pressureduring exercise is suggestive of acute myocardial impairment due toischemia. Dobutamine echocardiography and exercise testing revealeda higher overall sensitivity than dipyridamole echocardiography (79 vs 6 %,p < . In this situation, the test is a good, but notperfect, discriminator between patients with coronary artery disease andthose without disease. No major complicationsoccurred during the tests, but adverse effects were more frequent duringdobutamine testing. Thepatients with valve disease were found to have reduced tolerance forexercise and reduced maximal oxygen consumption during exercise. H., & Karunaratne, H. Use of the exercise testscore and decision-tree algorithms are helpful in clinical decision making.Importance of Problem Exercise electrocardiography is limited in its ability to predictprognosis accurately in patients with coronary artery disease (Krivokapich,Child, Gerber, Lem, & Moser, 1993, pp. At the end of the EST, data will be collected and recorded.Procedures Graded exercise testing on a treadmill requires the use ofstandardized protocols. This group includes most men and womenwith atypical chest pain, women with typical angina and asymptomatic men intheir 5 s or 6 s who have multiple risk factors. The results werecompared with those of 14 control subjects matched for age and sex. In the ANOVA performed for the proposed study, the EST and TMI outcomedata will be the dependent variable, while the test type (EST or EST/TMI)will be the independent variable. Exercise stress testing is associated with ahigher false-positive rate in women than in men (Evans & Karunaratne, 1992,pp. This finding was due to ahigher dobutamine and exercise sensitivity in one-vessel CAD (62 vs 33%, p< . Stress testing is about 7 percent sensitive and 8 percent specificfor coronary artery disease (Evans & Karunaratne, 1992, pp. -to 1.5-mm ST-segment depression is observed during thetest, the post-test likelihood of significant disease is still only 11percent. A greater fraction of the bloodwas being expelled from the left ventricle at rest among the stenosispatients. For most clinicians, this would represent anunacceptably high false-negative rate. Interpretation ofthe results. A., Rollan, M. The patient might thus be betterserved by proceeding to cardiac catheterization without a treadmill test. Many studies have found that hypotension associated with chestpain during exercise is indicative of severe coronary artery disease. These 1 subjects will be the research sample for theproposed study. The resultsindicate that abnormalities of exercise tolerance and heart function may bereadily detected among patients with valvular aortic stenosis, even if thepatients report no symptoms. Most studies have shown that, in patients with a test diagnostic ofmyocardial ischema, the test is 8 percent to 9 percent specific forcoronary artery disease (Evans & Karunaratne, 1992, pp. The decision of whether to perform a submaximal or maximal exercisetest also must be made (Evans & Karunaratne, 1992, pp. 5. 121-132). The doubleproduct (the systolic blood pressure multiplied by the heart rate)correlates closely with measured myocardial oxygen consumption duringexercise. Clinical Medicine [Germany],89(5), 233-239. 646-651). The variations betweenthe EST and TMI data then will be assessed within a pre-test/post-testanalytical format. A., Maron, B. Evans, C. Differences between womenand men in the dipridamole test. 5; 77 vs 6 %, p < . All subjects will complete an EST. Chest, 95, 139-144. Exercise stress testing is best used to evaluate patients whosepretest probability of disease is between 2 percent and 8 percent (Evans& Karunaratne, 1992, pp. Evans, C. Thus, the arbitrary figure of 85 percent of thepredicted value might only be 75 percent of a given patient's maximal heartrate. 679-688).Management of patients with the disease depends primarily on the locationand severity of the lesions identified on cardiac catherization. Comparison of dobutaminestress echocardiography, dipyridamole stress echocardiography and exercisestress testing for diagnosis of coronary artery disease. 865-87 ). Performing thetest. Krivokapich, J., Child, J. Although exercise stress testing in women may be of value for otherreasons, it is not recommended as a screening tool in asymptomatic women,even in those with coronary risk factors. 5 for both tests), whereas sensitivity of the 3 tests was similar inmultivessel CAD. An analysis using a cost/benefit model found littleadditional benefit from screening asymptomatic patients at average risk ofcardiovascular disease. 5), where the difference with dipyridamole (8 vs 7 %) was not significant. Pratt, Francis, Divine, & Young (1989, pp. The aortic valve separates the left ventricle and the aorta.When these symptoms are present, the surgical replacement of the valve isconsidered. J., Dilsizian, V., Bonow, R.O., & Cannon, R. (1989).Exercise testing in women with chest pain: Are there additional exercisecharacteristics that predict true positive test results? Each of the common protocols consists ofprogressive stages of work.
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