Troponin complements ED triage, cuts admissions

Cost avoidance is key to cost-effectiveness

The earlier you discover which chest pain patients can safely go home, the more you can save your facility. Effective triage is key. More than $3 billion is spent each year worldwide on patients ultimately found not to be having heart attacks.

The overwhelming majority of the 5 million or more patients who report to emergency departments (ED) with chest pain can be safely excluded from unnecessary expensive admissions by appropriate and timely triage. EKG measurements combined with continuous ST-segment monitoring, provocative testing, and careful clinical history are mainstays of the evaluation of patients in whom cardiac disease is clinically suspected. The rapid - under 20 minutes - bedside testing of troponin T and I proteins, highly sensitive markers of cardiomyocyte injury, can now routinely be added to that list. The resulting triage enables even isolated rural hospitals to avoid unnecessary admissions.

The advent of more sensitive specific tests for myocardial injury and the need to decrease expensive coronary care unit days for undifferentiated chest pain has led to a proliferation of chest pain evaluation centers. That approach makes sense when you consider that the sensitivity of testing increases over a finite period of observation. Physicians use tests with high negative predictive values during the first 12 hours following the onset of pain to rule out myocardial cell damage. Following that, provocative testing to put the heart in a situation of increased myocardial oxygen demand further increases sensitivity.

Troponin T (TnT) assays such as CARDIAC T by Boehringer Mannheim were the first troponin commercially available assays. The tests are administered at bedside, in stat labs adjacent to care areas, or in the central lab. They preceded the first troponin I (TnI) assays by a few years. Terry Prewitt, a Boehringer Mannheim spokesperson, says the TnT assay is third generation and significantly improved in terms of low end sensitivity, specificity, and turnaround time. The CARDIAC T rapid assay for TnT costs $20 to $30.

When asked about the cost, Joseph H. Keffer, MD, chief medical officer for Spectral Diagnostics in Toronto, Ontario, Canada, manufacturer of the "Cardiac Status" TnI device, says TnI and TnT tests cost about the same. "The relevant consideration," he says, "has to do with cost avoidance, not cost per test result. Money is saved on the patients who don't have to be admitted to the hospital. Physicians can be confident that the patient who is TnI negative and does not have a positive EKG or significant history can be sent home."

Investigators in Germany recently looked at 773 consecutive patients with normal levels of troponin to determine if they could be identified as being at such low risk they could safely be treated as outpatients.1

Study participants had acute chest pain but no ST segment elevation and no documented acute myocardial infarction (AMI) for two weeks. TnT and TnI tests were performed on arrival and four hours later. In patients who presented within two hours of chest pain onset, a third sample was obtained six hours after pain onset, so that all patients had at least one sample six or more hours after pain onset.

Serial creatine kinase-MB (CK-MB) testing documented AMI in 21 of the patients; 315 had unstable angina, 121 had stable angina, 12 had pulmonary embolism, 15 had heart failure, five had myocarditis, and 258 had no evidence of ischemic heart disease. All patients with AMI and unstable angina were admitted.

Both troponins were powerful predictors of subsequent events as compared to CK-MB, EKG ST segment depression, or EKG T-wave inversion. (For results of the trial, see story, at left.) The investigators concluded that the new rapid troponin tests, especially TnI, are highly sensitive for detecting myocardial injury in acute coronary syndromes, and negative tests are associated with low enough risk to permit safe discharge from the ED after an episode of chest pain. Results of the German study confirmed that testing in the ED allows rapid, safe, and money-saving discharge of patients.

TnI outperforms TnT

TnI assays performed better than TnT assays in the study. TnI detected all patients with AMI, whereas the TnT was positive in only 44 out of 47 cases, and the TnT yielded six false positives. TnI tests were positive in 22% of patients, and TnT tests were positive in 16%. No cardiac event occurred in 30 days in a study patient with a normal EKG who also had a negative TnI test. Investigators say the implication of a positive TnI test is that "all patients with at least one positive test result should be admitted and require further evaluation including coronary angiography in most cases."

"The troponin tests cannot replace clinical evaluation of the patient with chest pain," they add. "However, this new diagnostic tool with its superior predictive value should be made available to emergency departments and chest pain units."

Michael H. Crawford, MD, chief of cardiology at the University of New Mexico in Albuquerque, says most hospitals now use troponin tests. The German study extends previous study results in two ways:

1. The rapid qualitative test results are as good as the more laborious quantitative tests.

2. The concept of using troponins to triage in the ED setting seems valid.

"Patients with positive tests clearly had more events and deserved further evaluation - usually as inpatients," Crawford says. "Patients with negative tests had a low risk of events at 30 days. The data suggest that two negative tests, or one at six or more hours after pain onset, identify a very low-risk group that can be safely discharged. Many of these patients may need further evaluation, but it can be done in the outpatient setting."

No substitute for the basics

Despite those impressive results, the study investigators point out that the troponins are not a substitute for the use of history, physical examination, and EKG.

The EKG is especially valuable for the immediate triage of the AMI patient to chemical or mechanical revascularization. Patients without obvious AMI do not benefit from thrombolysis, but these patients need careful evaluation to exclude other life-threatening illnesses such as aortic dissection. Also, the true cost savings of a six-hour ED triage protocol using troponins has not been established.

Observation for another six hours with serial CK-MBs may be as cost-effective and certainly is of equivalent accuracy, Crawford says. In addition, other tests, such as an exercise EKG, may be required to safely discharge the patient. "The rapid troponin assays are clearly a significant advance, and I agree with [the investigators] that every [ED] should have access to them."

The value of this study over many previous ones is that it took place in an ED setting with acute chest pain patients, says Jeffrey W. Runge, MD, clinical research director of the department of emergency medicine at Carolinas Medical Center in Charlotte, NC. The study confirms that troponin tests are more sensitive for minimal myocardial injury than CK-MB or EKG.

"Troponin testing does not, however, enable us to triage chest pain patients to admission or discharge after a single evaluation," says Runge. "Troponin testing is not useful as a screening tool as a single measurement shortly after the onset of chest pain."

Using any combination of tests with less than a 100% negative predictive value in a disease with fatal consequences is less than ideal, he adds. "The public has zero tolerance for error in this regard, and we must, therefore, be vigilant in our pursuit of this diagnosis. There is no magic test for early triage and no substitute for clinical judgment and the rational application of diagnostic testing over an appropriate period of time."

Reference

1. Hamm CW, Goldmann BU, Heeschen C, et al. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997; 337:1,648-1,653.

Suggested reading

Lopez-Jimenez F, Goldman L, Sacks DB, et al. Prognostic value of cardiac troponin T after noncardiac surgery: 6-month follow-up data. J Am Coll Cardiol 1997; 29:1,241-1,245.

Lindahl B, Venge P, Wallentin L for the Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. J Am Coll Cardiol 1997; 29:43-48.

Lauer B, Niederau C, Kühl U, et al. Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol 1997; 30:1,354-1,359.