HPI: The patient is a 48-year-old female with episodic chest discomfort over the last 3 days. She describes the discomfort as a substernal “ache” with intermittent radiation to the left shoulder, with associated shortness of breath, occurring primarily at rest and not exacerbated with physical exertion or eating. She has had multiple episodes lasting between 5 and20 minutes with spontaneous relief; however, the episode prior to presentation was particularly intense, lasting 60 minutes, prompting the ED visit. Upon presentation to the ED, she was symptom-free; the onset of the last episode was 3 hours prior to presentation.
Risk factors: Hypertension, tobacco use, father had an MI at age 54
PE: VS BP 130/80 mmHg, HR 82 bpm, RR 12
Normal cardiac and lung exam ECG: Sinus, without ST-T wave changes cTnI: <0.04 ng/ml (Siemens cTnI-ultra) at presentation and 3 hours
The patient was moved to the chest pain observation unit after the first cTnI value, with subsequent stress testing prior to being discharged ordered.
When can the patient proceed to stress testing?
The correct answer is: A. Now without any further measurement of cTnI
The measurement of either cTnI or cTnT is the preferred marker to be used in the evaluation of a patient with undifferentiated chest pain. There is, however, no clear consensus over the exact period of time that serial sampling should occur. The most common recommendations are to measure a second marker at 6-9 hours after presentation.(1, 2) In a study from more than 10 years ago using a much less sensitive cTnI assay, patients with normal cTnI values at 6 hours after symptom onset had an adverse event rate of only 0.3 %.(3) With our patient, the sample at 3 hours was 6 hours after symptom onset.
Some early single-center studies suggested that the time interval for serial sampling could be decreased from 6 to 3 hours.(4) A multi-center trial published in 2009 demonstrated early high sensitivity with newer more sensitive cTnI and cTnT assays. This study demonstrated a sensitivity of 89% for AMI at presentation with the assay used in our patient. Serial sampling showed that the diagnostic utility was optimal at 3 hours and not improved by sampling at 6 hours. Another study utilizing a newer high-sensitivity cTnT assay had 100% sensitivity for AMI at 3 hours.(5) Interestingly, a recent study found that a normal cTnT at the time of presentation using the newest high-sensitivity assay essentially excluded MI, a finding present in 28% of patients.(6)
An important consideration is that risk is also dependent on the pre-test probability of disease. For low risk patients, the likelihood of MI is typically under 5%. Coupling this low initial risk with a high sensitive assay further reduces the likelihood of MI, such that stress testing can occur at earlier time points. Our patient had atypical symptoms, with no history of CAD. In conjunction with a normal cTnI value at 3 hours, which was at 6 hours after symptom onset, indicates she can proceed safely onto stress testing.
As we learn more about the high sensitivity cTn assays the amount of time required for serial sampling will continue to decrease. There are ongoing trials investigating protocols that could exclude AMI in even less than 3 hours with newer high sensitivity cTnI and cTnT assays.
Hamm, C.W., et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2011; [Epub Ahead of Print].
Morrow, D.A., et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem 2007; 53:552-74.
Hamm, C.W., 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; 337:1648-53.
Macrae, A.R., et al. Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies. Clin Chem 2006; 52:812-8.
Giannitsis, E., et al. High-sensitivity cardiac troponin T for early prediction of evolving non-ST-segment elevation myocardial infarction in patients with suspected acute coronary syndrome and negative troponin results on admission. Clin Chem 2010; 56:642-50.
Body, R., et al. Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay. J Am Coll Cardiol 2011; 58:1332-9.