STRESSED ABOUT STRESS TESTS Problem Based Lecture Jennifer W. Hsieh Department of Emergency Medicine PGY-3
Question 6 What is the diagnostic accuracy of cardiac testing in low risk chest pain patients? What is the prognostic value of negative provocative testing and negative cardiac imaging?
The Bigger Question Do we need to evaluate low risk chest pain patients in the ED with provocative testing?
Objectives Overview of several modalities available for confirmatory cardiac testing- with Dr. Pflaum Review of literature regarding the accuracy and prognostic values of these tests Exercise Treadmill Test (ETT) Myocardial Perfusion Index (MPI) Stress ECHO Coronary CT Angiography (CCTA) Will NOT discuss cardiac MRI, PET and Catheterization
The Sources
The Sources
What is Exercise Treadmill Testing? Patient exercises on treadmill under supervision of trained professional Monitored for abnormalities suggesting exercise induced ischemia Symptoms EKG changes Blood pressure Arrhythmias Must achieve adequate heart rate of at least 85% agepredicted maximum
From nhlbi.nih.gov
What is an MPI? Nuclear study used to detect abnormalities in myocardial perfusion (SPECT) Thallium-201 Technetium Tc 99m Sestamibi (Cardiolite), tetrofosmin (Myoview) Rest vs. Stress Irreversible (infarction) vs. reversible (ischemia) Exercise vs. chemical stress Hand grip, treadmill, vasodilator (dipyridamole, adenosine, regadenoson)
Quantitative analysis vs. expert visual analysis From Braunwald s: figure 17-26
What is a Stress ECHO? ECHO obtained after stress, compared to ECHO at rest to detect wall motion abnormalities and perfusion defects suggestive of inducible ischemia Exercise vs. chemical stress Treadmill, bicycle, dobutamine, dipyridamole, adenosine
From Braunwald s: figure 13-35
What is CT Coronary Angiography? High resolution CT imaging of coronary arteries From Braunwald s: figure 19-13
Coronary Artery Calcium Scanning Uses coronary calcium as marker for atherosclerosis From Braunwald s: figure 19-10
What to Order When?
How Good is Exercise Treadmill Testing? Braunwald s Sensitivity 68%, Specificity 77% for patient s selected to undergo angiography Several series of clinically low-risk subjects have reported 6 month cardiac event rates lower than 1% with a normal exercise test result.
Duke Treadmill Score Prognosis related to the Duke Treadmill Score Exercise duration Degree of ST segment deviation Presence/severity of angina DTS= exercise time - (5xST deviation) - (4xangina)
Duke Treadmill Score and Survival 5 year mortality Low risk: 3% Moderate risk: 10% High risk 35% UpToDate
Studies of Exercise Treadmill Testing in Accelerated Diagnostic Protocols
Objective To determine the safety and accuracy of immediate exercise testing in low risk patients presenting to the emergency department with chest pain suggestive of a cardiac etiology.
Study Design Single center prospective trial Patients n = 1,000 Considered low clinical risk (hemodynamically stable, no arrhythmias, no evidence of acute cardiopulmonary process on exam, CXR, EKG) Could have persistent pain
Study Design Testing Performed by trained attending internists immediately after initial evaluation +/- one troponin Modified Bruce protocol If negative, discharged; if positive admitted; if non-diagnostic some discharged, some admitted to chest pain unit (34% got further work-up)
Study Design Follow-up At 30 days (review of medical record, phone, mailed questionnaires, coroner s records, social security death index) Overall obtained 89% follow-up (85% clinically, additional 4% due to presence of additional testing)
Results No adverse effects from testing No mortality in any patient Negative in 64%, positive in 12.5%, nondiagnostic in 23.5%
Event rates/diagnosis of CAD: 0.3% in negatives 29% in positives (RR =114) 13% in non-diagnostics (RR = 38)
Conclusions Immediate exercise testing of patients presenting to the ED with chest pain and evidence of low clinical risk is safe and accurate for determining those who require admission and those who can be discharged to further outpatient evaluation.
Limitations What happened to the patients lost to follow-up? (58 negatives, 29 positives, 52 non-diagnostics lost to follow-up) No long-term follow-up: benefits of CAD detection/revascularization unclear Outcome measures of MI, revascularization and diagnosis of CAD No serial troponins
My Conclusions
If Then
How Good is an MPI? Braunwald s Cites 2003 ACC/AHA/ASNC Radionuclide Imaging Guidelines Sensitivity 87% (71-97%), specificity 73% (36%-100%) Patients with normal study have 0.7% rate of MI/cardiac death over 2 years When CAD present with stable symptoms patients with normal study have 0.9% cardiac events/year
Diagnostic Accuracy of Rest MPI in Patients with Acute Chest Pain and a Nonischemic EKG
Objective To assess whether incorporating acute resting perfusion imaging into an ED evaluation strategy for patients with suspected acute ischemia but no initial ECG changes diagnostic of acute ischemia improves clinical decision making for initial ED triage.
Study Design Multi-center prospective randomized controlled trial Patients: n = 2475 7 academic medical centers and community hospitals 30 years or older (18 years or older if + cocaine) with symptoms suggesting acute ischemia within 3 hours and with normal/nondiagnostic initial EKG Patients with history of MI excluded
Study Design Randomization Usual strategy vs. usual strategy + results from scan (rest MPI using SPECT) 47% women in scan group, 51% usual care (p 0.03) otherwise no statistical difference between groups in terms of demographics and risk factors Testing Scan patients quickly injected with sestamibi Imaged 30 min + after injection Results reported to ED physician (normal, abnormal, equivocal) as soon as available who used data in determining disposition
Study Design Final diagnosis ECGs, cardiac enzymes, follow-up stress testing for all Admitted: in hospital Discharged: 24-36 hours later Final diagnosis determined by site PI (blinded) Follow-up At 30 days: for vital status, cardiac events, need for procedure 99% complete
Results 13% with acute ischemia (2% AMI, 11% UA) No difference in appropriate hospitalization rates for patients with UA/AMI 1 missed AMI in each group (p=0.92) 26 missed UA in scan group, 23 in usual care (p=0.58) No difference in outcomes at 30 days Fewer unnecessary hospitalizations in scan group- 42% vs. 52% (RR 0.84%, 95% CI 0.77-0.92, P< 0.001)
Results No difference in outcomes at 30 days
Results MPI results had prognostic value Risk AMI at 30 days 0.6% in normals, 0.8% in equivocals, 10.3% in abnormals (RR 6.61 for equivocal/abnormal compared to normal, p < 0.001) Risk cardiac event at 30 days 3.0% in normals, 6.1% in equivocals, 20.5% in abnormals (RR 3.83 for equivocal/abnormal compared to normal, p <0.001)
Conclusions Sestamibi perfusion imaging improves ED triage decision making for patient with symptoms suggestive of acute cardiac ischemia without obvious abnormalities on ECG. In this study, unnecessary hospitalizations were reduced among patients without acute ischemia, without reducing appropriate admission for patients with acute ischemia.
Limitations End-point of study is appropriateness of ED disposition decision- assumes only reason to admit is to rule out ACS Diagnosis of ACS/MI may not be objective No long-term follow-up End-points for cardiac events: death, MI, revascularization
My Conclusions Well executed study to answer question of whether rest MPI helps with patient disposition in the ED Demonstrates good short-term prognostic value of negative rest MPI
How Good is a Stress ECHO? Braunwald s Comparable to nuclear studies Sensitivity 85%, specificity 88% (study?) Cites Mayo Clinic study: event rate of less than 3% at 3 year follow up after a negative study
Predictive Accuracy of Stress ECHO in Patients Presenting to the ED with Chest Pain
Objective We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram and a negative serial troponin T.
Study Design Multi-center prospective double-blind trial Patients n = 377 Patients with chest pain within 6 hours of presentation with a normal/non-diagnostic ECG Excluded: younger than 18, unable to give consent, a-fib, conduction disturbances, severe HTN, severe CHF, requiring resuscitation, serious non-cardiac disease, pregnant Initial evaluation H&P, serial EKG, continuous cardiac monitoring, serial troponins, observation for at least 12 hours
21% with ACS after initial evaluation!
Study Design Testing IV dobutamine given in increasing dose increments per protocol (max 40 mcg/kg/min) End points: severe and/or extensive new wall motion abnormality, target HR, tachyarrhythmias, ECG changes, CP, BP > 240/120 or sbp decrease 40 mmhg, intolerable sideeffects Atropine prn to achieve 85% age predicted maximal heart rate or if endpoints not achieved Beta blocker prn to reverse effects Results reported as positive and negative (read by two experienced investigators, if disagree third read obtained) Positive if new wall motion abnormality in at least 1/16 LV segments
Study Design Follow-up At 6 months, follow-up clinic visit 100% complete End points Primary: cardiac death, nonfatal AMI, rehospitalization for UA Secondary: revascularization
Results
Results 26 positive, 351 negative Target HR achieved in 80.1%; Test not completed in 19.9% (developed exclusion criteria) DSE results had prognostic value: Positive test gives OR of 6.2 (95% CI 1.6-24.3) for primary endpoint and OR of 7.1 (95% CI 2.5-20.2) for combined end point At 6 months risk of cardiac event 30.8% in positive group, 4% in negative group (p < 0.0001)
Conclusions Conclusions: A predischarge DSE had important, independent prognostic value in low-risk, troponin negative, chest pain patients.
Limitations Multiple end-points for cardiac event some more serious that others (e.g. death vs. rehospitalization for UA) Patients are higher risk than what we consider low-risk Non-diagnostic tests categorized as negative
My Conclusions Another confirmatory test with similar sensitivities and specificities to treadmill testing and MPI In practice in the U.S. unlikely only 26/377 (<7%) will be read as positive 4% cardiac event rate in negatives at 6 months may be too high in current U.S. medical climate
How Good is CT Coronary Angiography? Braunwald s Sensitivity 87-99%, specificity 93-96% (Mowatt et. al.) Little information regarding prognosis
Objectives To determine the usefulness of coronary CT in determining whether discharge of patients from the emergency department is safe.
Study Design Multi-center prospective randomized controlled trial Patients n= 1370 5 sites Low-intermediate risk 30 years or older with TIMI score 0-2, no acute ischemia on ECG Excluded non-cardiac etiology of symptoms, co-existing condition requiring admission, negative cath or CCTA in past 1 year, contraindications to CCTA Randomization 2:1 (CCTA:traditional care)
Study Design Testing 64-slice or greater multi-detector CT scanner able to perform ECGsynchronized cardiac studies Beta blocker for HR control, nitroglycerin for coronary artery dilatation per protocols Non-contrast scan for calcium scoring, contrast scan Results classified as: no stenosis, stenosis less than 50%, stenosis of 50-69%, stenosis of 70% or more Significant CAD= 50% or more stenosis of main coronary arteries or first order branch Indeterminate if negative but with inadequately visualized segments All had second troponin drawn prior to discharge
Study Design Follow-up 100% complete Phone follow-up up at least 30 days later Review of records in local hospitals for repeat visits Social Security Death Master File
Results Results of testing
Results Safety CCTA group 10/908 (1%) had MI within 30 days 0% had death within 30 days 0% with negative CCTA had death or MI within 30 days (95% CI 0-0.57) 1 adverse event (bradyarrhythmia) Traditional group 5/462 (1%) had MI within 30 days 0% had death within 30 days 1 adverse event (bradyarrhythmia)
Results More CCTA patients discharged (49.6% vs. 22.7%, 26.8 percentage points, 95% CI 21.4 to 32.2), shorter length of stay More CAD diagnoses in CCTA group (9.0% vs. 3.5%, 5.6 percentage points, 95% CI 0-11.2) No difference in angiography and revascularization rate, ED/cardiology clinic visits or hospitalizations after 30 days
Conclusions Conclusions: A CCTA-based strategy for low-to-intermediate-risk patients presenting with a possible acute coronary syndrome appears to allow the safe, expedited discharge from the emergency department of many patients who would otherwise be admitted.
Limitations 16% randomized to CCTA did not get CT (unable to adequately beta block, transition of care) No long-term follow-up No information regarding potential harms of CCTA
My Conclusions Shows a negative CCTA can be helpful in ED disposition Implications of a positive CCTA yet to be determined
What Do These Tests Add? What is the diagnostic accuracy of cardiac testing in low risk chest pain patients? Not good enough! Reported range of sensitivities for ETT, MPI and ECHO 68-87%; specificities 73-88% ETT MPI Stress ECHO CCTA Sensitivity 68% 87% 85% 87-99% Specificity 77% 73% 88% 93-96%
A test needs to be very sensitive (few false negatives) if we are using it to further risk stratify ACS in a low risk population A test needs to be very specific (few false positives) if we do not want to be overwhelmed by the need to work-up false positives Low accuracy of confirmatory testing reviewed is not good enough to tell us whether low risk patients have ACS- of the ones who test positive most do NOT have ACS.
The primary purpose of confirmatory testing as part of an accelerated diagnostic protocol during CPU observation is to further minimize the likelihood of ACS to a level so low that discharge is safe. - Amsterdam et. al.
What is the prognostic value of negative provocative testing and negative cardiac imaging? Prognosis of low risk chest pain patients is generally good Confirmatory testing can help further reassure that prognosis is excellent and patient can be discharged
Are We Still Stressed About Stress Tests? Do we need to evaluate low risk chest pain patients in the ED with provocative testing?
References Original Articles Amsterdam EA, Kirk JD, Diercks DB, Lewis WR, Turnipseed DS. Immediate exercise testing to evaluate low-risk patients presenting to the emergency department with chest pain. J am Coll Cardiol. 2002;40:251-256. Bholasingh R, Cornel JH, Kamp O, van Straalen JP, Sanders GT, Tijssen JG, Umans VA, Visser CA, de Winter RJ. Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponin T. J Am Coll Cardiol. 2003;41:596-602. Litt HI, Gatsonis C, Snyder B, Singh H, Miller CD, Entrikin DW, Leaming JM, Gavin LJ, Pacella CB, Hollander JE. CT angiography for safe discharge of patients with possible acute coronary syndromes. N Engl J Med. 2012;366:1393-1403. Shaw LJ, Peterson ED, Shaw LK, Kesler KL, Delong ER, Harrell FE, Muhlbaier LH, Mark DB. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation. 1998;98:1922-1630. Udelson JE, Beshansky JR, Ballin DS, Feldman JA, Griffith JL, Handler J, Heller GV, Hendel RC, Pope JH, Ruthazer R, Spiegler EJ, Woolard RH, Selker HP. Myocardial perfusion imaging for evaluation and triage of patients with suspected acute cardiac ischemia. JAMA. 2002;288:2693-2700.
References Guidelines AHA Scientific Statement: Testing of Low-Risk Patients Presenting to the Emergency Department with Chest Pain. (2010) ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide Imaging Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force of Practice Guidelines. (2003)
References Books Libby, P., & Braunwald, E. (2012). Braunwald's heart disease: A textbook of cardiovascular medicine. Philadelphia: Saunders/Elsevier. Chizner M. (2007). Clinical cardiology made ridiculously simple. Miami: MedMaster.