By Michael H. Crawford, MD

Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: In patients with new-onset chest pain without ECG evidence of an ST-elevation myocardial infarcition, conversion to the use of a high-sensitivity troponin T assay with three-hour retesting in three hospitals was compared to maintaining the fourth-generation troponin T assay with six-hour retesting in three other hospitals. The use of high-sensitivity troponin T resulted in lower ED length of stay and costs, without increasing the use of coronary angiography or stress testing.

SOURCES: Twerenbold R, Jaeger C, Rubini Gimenez M, et al. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J 2016;37:3324-3332.

Crea F, Jaffe AS, Collinson PO, et al. Should the 1h algorithm for rule in and rule out of acute myocardial infarction be used universally? Eur Hear J 2016;37:3316-3323.

Januzzi JL. Troponins in equipoise. Eur Heart J 2016;37:3333-3334.

Although the introduction of high-sensitivity troponin assays in some health systems has decreased the time necessary to accurately diagnose an acute myocardial infarction (MI), there has been concern that its use would lead to an increase in inappropriate coronary angiography. Investigators from the Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) study assessed the effect of switching from fourth-generation troponin T assays to high-sensitivity troponin T(hsTnT) on use of coronary angiography, cardiac stress testing, and time to ED discharge in three hospitals in Europe. Three hospitals in APACE who did not switch were used as controls. Patients in the ED with chest pain for less than 12 hours that was suggestive of acute MI were recruited. Those with ECG ST elevation MI or end-stage renal disease on dialysis were excluded. The troponin T protocol required repeat testing at six hours and the hsTnT protocol after three hours. Of the 2,544 patients entered over about six years, 57% were enrolled before and 43% after the switch. There were baseline characteristic differences in the patients between the two study periods, and there was an increase in the diagnosis of acute MI in the second period (14% vs. 10%; P < 0.001). Also, there was a corresponding decrease in the diagnosis of unstable angina from 14% to 9%, but the overall acute coronary syndrome (ACS) rate was unchanged (24% vs. 23%; P = NS). In addition, the discharge diagnosis of chest pain of unknown origin decreased from 48% to 38% (P < 0.001). The rate of coronary angiography was identical between the two phases (23%), and the rate of stress testing was similar (12% vs. 10%). Finally, ED length of stay was reduced in the hsTnT group by 79 minutes (P < 0.001), and costs were reduced 20% (P = 0.002). There were no significant changes in these parameters in the control group over the same two time periods. The authors concluded that the use of hsTnT did not increase the use of coronary angiography or stress testing, but did reduce ED length of stay and costs.

COMMENTARY

Current troponin assays used in the United States are imprecise at low values where the risk of missing an early non-ST segment myocardial infarction is highest. In addition to the usual clinical and ECG data, the six-hour troponin retest has been advanced to overcome this problem. The advent of high-sensitivity troponin tests has allowed for a three-hour retest protocol to perform similarly to the six-hour protocol. However, there has been resistance to adopting the three-hour test protocol because of concerns that it would generate considerable false positives and would increase costs and inappropriate coronary angiography. The adoption of the hsTnT with a three-hour protocol in three hospitals in the APACE research consortium allowed the investigators to compare their experience to experiences of the hospitals still using the standard troponin T six-hour protocol. Although not a randomized trial, the results are compelling. Coronary angiography and stress testing rates remained constant, and ED length of stay decreased significantly. There were no changes in these parameters over the same time frame in the control hospitals. The authors argued that adoption of the three-hour retest in the hsTnT protocol improved the precision of allocating patients for further testing or discharge home.

There are limitations to the study. There were baseline differences between the patients before and after the switch in the test hospitals, which the investigators adjusted for, but a propensity analysis was not performed. Also, only troponin T was studied, so the results may not be applicable to troponin I. In addition, patients with end-stage renal disease on hemodialysis were excluded. It is well known that troponin T levels are higher in such patients, which adds complexity to the use of the three-hour protocol, were it to be used more widely. Finally, there are no outcome data, so we don’t know if the three-hour protocol resulted in better care.

The most recent European Society of Cardiology guidelines recommend a one-hour retest protocol with high-sensitivity troponin, which wasn’t tested in this study, but there are other data supporting its use. The expected changes in high-sensitivity troponin over one hour usually will be less than that seen with three- or six-hour retest protocols, raising the concern that specificity will be less due to the difficulty in interpreting small rises in troponin. If this is the case, the one-hour protocol could increase angiography and other costs. Clearly, the barriers to high-sensitivity troponin testing are falling, and I would anticipate adoption of these tests in the United States in the near future. In appropriate patients where non-ST elevation acute MI is highly likely clinically, these tests could increase the rapidity of diagnosis and appropriate treatment. However, we know from our experience with fourth-generation troponin testing that the test will be applied widely to largely inappropriate patients, worsening the current troponimania we are dealing with now.