• 
• 

Three Part Question

In [patients with suspected cardiac chest pain] does [serial measurement of CK-MB plus serial electrocardiography] allow [early rule out of myocardial infarction]?

Clinical Scenario

A 35 year-old man presents to the Emergency Department two hours after experiencing an episode of central squeezing chest pain lasting thirty minutes. Initial ECG is normal. You wonder whether serial measurement of CK-MB plus serial electrocardiography will allow you to effectively rule out myocardial infarction (MI), thus avoiding admission for troponin testing at twelve hours.

Search Strategy

OVID Medline 1966 - 2005 July Week 1
OVID EMBASE 1980 - 2005 Week 29
[exp Myocardial Infarction/ OR myocard$ adj infarct$).mp. OR heart attack.mp. OR AMI.mp. OR MI.mp. OR exp Coronary Thrombosis/] OR [exp Creatine Kinase/ OR CK-MB.mp.] AND [exp Early Diagnosis/ OR exp Diagnosis/ OR diagnosis.mp. OR exp Diagnosis, Differential/] AND [exp Electrocardiography/ OR ST segment.mp. OR S-T segment.mp. OR ECG.mp. OR EKG.mp.] limit to human and English language

Search Outcome

Altogether 403 papers were found using Medline and 257 using EMBASE. Three papers were relevant to the three-part question, all of which were found using both Medline and EMBASE.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Herren et al 2001 United Kingdom	292 patients (aged over 25) presenting to the Emergency Department with suspected cardiac chest pain lasting less than 12 hours and with no initial ECG evidence of MI or ischaemia	Prospective observational study	Performance of diagnostic protocol for diagnosis of MI	Sensitivity 97.2%; Specificity 93.0%; LR+ 13.9; LR- 0.03. Given a pre-test probability (study prevalence) of 12.3%, post-test probability (given -ve test) is 0.4.	24% of patients didn't complete the study. This could have biased the results, although it is unlikely that many of them had MI.
Fesmire FM 2000 United States	706 consecutive patients presenting to the Emergency Department with suspected cardiac chest pain. All patients had serial ECG monitoring and CK-MB at presentation and 2 hours. Diagnosis of MI according to WHO criteria. Follow up at thirty days.	Prospective observational cohort	Initial ECG for diagnosis of MI	Sensitivity 39.8%; Specificity 98.7%; LR+ 31.0; LR- 0.61. Given pre-test probability (study prevalence) of 10.8%, post-test probability (if test -ve) 6.9%	Delayed presentations not excluded. Mean symptom duration in MI group 2.0+/- 2.8 hours (range 10 minutes to 18 hours).
			Initial ECG + baseline CK-MB for diagnosis of MI	Sensitivity 55.4%; Specificity 98.6%; LR+ 38.4; LR- 0.45. Post-test probability (if test -ve) of 5.2%
			Initial ECG + baseline CK-MB + serial ECG for diagnosis of MI	Sensitivity 74.7%; Specificity 97.0%; LR+ 24.5; LR- 0.26. Post-test probability (if test -ve) of 3.1%
			Initial ECG + serial ECG + 2-hour delta CK-MB for diagnosis of MI	Sensitivity 94.0%; Specificity 93.6%; LR+ 14.6; LR- 0.06. Post-test probability (if test -ve) of 0.7%
Young et al 1997 United States	1043 consecutive patients presenting to the Emergency Department with suspected cardiac chest pain and non-diagnostic ECG's on admission. Blood sent for CK-MB at presentation and 3 hours. ECG at presentation and 3 hours. CK-MB >=8ng/ml considered positive. ECG's interpreted for ST elevation Diagnosis of MI according to WHO criteria using CK-MB levels. Follow up at 24-48 hours.	Prospective observational cohort	Presenting CK-MB for diagnosis of MI	Sensitivity 56.7%; Specificity 96.6%. LR+ 16.7, LR- 0.45. Given a pre-test probability (study prevalence) of 6.4%, post-test probability (given -ve test) is 3.2%.	1043 patients included, results reported for 1042. Gold standard MI diagnosis utilised CK-MB as the gold standard biochemical marker. Number of patients lost to follow up was not reported. It was assumed that none of these patients had missed MI. Delayed presentations were not excluded. Mean symptom duration by time of venepuncture in the MI group was 6 hours. Increasing sensitivity of CK-MB with time, which may have biased results.
			Presenting and/or 3h CK-MB for diagnosis of MI	Sensitivity 88.1%; Specificity 95.8%; LR+ 21; LR- 0.124; Post-test probability (if test -ve) 0.9%
			Abnormal CK-MB(s) or CK-MB rise (>=3ng/ml while in normal range) for diagnosis of MI	Sensitivity 92.5%; Specificity 95.2%; LR+ 19.3; LR- 0.08; Post-test probability (if test -ve) 0.6%
			Abnormal CK-MB(s) or CK-MB rise or 3-hour ECG develops ST elevation for diagnosis of MI	Sensitivity 95.5%; Specificity 95.4%; LR+ 20.8; LR- 0.05; Post-test probability (if test -ve) 0.3%

Comment(s)

Chest pain accounts for 2-4% of all admissions to the Emergency Department in the United Kingdom (Fothergill et al, 1993). It is not possible to accurately rule out myocardial infarction using clinical features alone. Unexplained chest pain that may be cardiac in origin therefore warrants further investigation. Troponin estimation provides the gold standard for diagnosis of MI. However, it is insufficiently sensitive until at least 12 hours after symptom onset (Richell-Herren et al, 2000). Many Emergency Departments have therefore investigated the utility of Chest Pain Adimssion Units that may allow earlier exclusion of MI. The strategy of serial CK-MB plus serial electrocardiography has been shown to be a sensitive tool for this purpose. It is likely to perform best when applied to a low-risk population with a low incidence of MI.

Clinical Bottom Line

Serial CK-MB plus serial electrocardiography provide a sensitive tool for early rule out of myocardial infarction and are best applied to the low risk population.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. Herren KR; Mackway-Jones K; Richards CR; Seneviratne CJ; France MW; Cotter L Is it possible to exclude a diagnosis of myocardial damage within six hours of admission to an emergency department? Diagnostic cohort study British Medical Journal 2001; 323: 372-375
2. Fesmire FM A rapid protocol to identify and exclude acute myocardial infarction: continuous 12-lead ECG monitoring with 2-hour delta CK-MB American Journal of Emergency Medicine 2000; 18: 698-702
3. Young GP; Gibler B; Hedges JR; Hoekstra JW; Slovis C; Aghababian R; Smith M; Rubison M; Ellis J; for the EMCREG II Study Group Serial creatine kinase-MB results are a sensitive indicator of acute myocardial infarction in chest pain patients with nondiagnostic electrocardiograms: the second emergency medicine cardiac... Academic Emergency Medicine 1997; 4: 867-877
4. Richell-Herren K; Maurice S Troponin T does not rule out myocardial damage until 12 hours after the onset of chest pain Emergency Medicine Journal 2000; 17: 213-214
5. Fothergill NJ; Hunt MT; Touquet R Audit of patients with chest pain presenting to an accident and emergency department over a 6-month period Archives of Emergency Medicine 1993; 10: 155-160