- Email: [email protected]
Markers for early diagnosis of myocardial infarction
THELANCET
AMI (n=,15)
thresholds required to rule-in or rule-out such a diagnosis are different. 2 Third, the rule-out decision threshold varies with the time after the onset of symptoms? Finally, combination testing--ie, testing in series or parallel m o d e - - c a n increase test sensitivity or specificity.3 None of these aspects appear to have been addressed in Bakker's study. Studies by others" and ourselves (unpublished) contradict Bakker's claim. Out results indicate that all these analytes are highly effective at time after the onset of symptoms earlier than Bakker's 10 h limit (table). We conclude that myoglobin is a useful early marker and that CK-2 (mass) and troponin T are later, but equally effective, markers for MI.
noAMI (n=69)
non~i~n~onAP AD delay
<3h/~3h
i
I
CKM/~mass
noacute acute is~hemia i~hcmia
~AMI
Vipin Bhayana,A Ralph Henderson
~6.7 >6.7
noAMI
AI~
Department of Clinical Biochemistry, UniversityHospital (Universityof Western Ontario), London,Ontario N6A 5A5, Canada
1 Leung FY, Galbraith LV, Jablonsky G, Henderson AR. Re-evaluation of the diagnostic utility of serum total creatine kinase and creatine kinase-2 in myocardial infarction. Clin Chem 1989; 35: 1435-40. 2 Leung FY, Griffith AP, Jahlonsky G, Henderson AR. Comparison of the diagnostic utility of timed serial (slope) creatine kinase measurements with conventional serum tests in the early diagnosis of myocardial infarction. Ann Clin Biochem 1991; 28= 78-82. 3 Cebul RD, Hershey JC, Williams SV. Using multiple tests: series and parallel approaches. Clin Lab M e d 1982; 2: 871-90. 4 Muir J, Armer-Dworzak E, Lechleimer P, et al. Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin. Br Heart ff 1992; 68: 462-68.
[AM]
ECG
A
no acute
acute
ischemia ischetnia
non-Qwave
Q v/ave
Figure: Binary decision tree for MI For ECG criteria required for the diagnosis "acute ischaemia" see text. The number of patients with Q wave MI fulfilling decision criteria is given in the upper left quarter, with nen-Q wave AMI in the lower left, with angina pectoris (AP) in the upper right, and with chest pain not related to coronary artery disease (non-CAD) in the lower right quarter of circles.
contingency table was 88"2 (95% CI 25-7-303"2, p < 0-0001). T h e decision tree established in this study can help to guide patients' care and should be prospectively evaluated by other hospitals. Johannes Mair Inatitut for Medizinische Chemie und Biochamie. Fritz-Preglstrasse 3, A-6020 fnnsbruck,Austria
World Health Organization criteria for the diagnosis of acute myocardial infarction. Proposal for the multinational monitoring of trends and determinants in cardiovascular disease. Geneva: WHO, Cardiovascular Disease Unit, 1981.
S I R - - T h e claim by Bakker and colleagues that t h e measurement of myoglobin, C K - 2 (mass), and troponin T do not allow exclusion of M I within 10 h has serious flaws. First, they use each test's upper reference limit without defining the population used for its derivation. We have shown that conventionally-derived ranges are inappropriate for diagnostic purposes in coronary care units. I Second, the decision Test
Rule-out deslskm threshold
'time(h)*
Kernel Simon
0-3
3-6
6-9
9-12
45 (80-St)
82 (68-91) 81 (46-75) 85 (40-69)
95 (N-88) 81 (81-97) 91 (91-97)
95 (M-t00) 98 (86-100) 98 (M-IO0)
(p/L) Myoglobln
74
CK.2(mass)
8.0
12
TmponlnT
0'1
(4-26) 24 (12-39)
Populationcomprised65 patie0tswith MI and 60 without. *Fromonsetof symptoms.
Table: Test sensltMtles of (95% CI) myoglobln, CK-2 (mass), and troponin T
1554
SIR--Bakker and colleagues found that even the newer markers (myoglobin, troponin T) and methods ( C K - M B mass concentration) have too low sensitivity and specificity in verificatibn of M I during the first 10 h after onset of chest pain. I do not suppose the authors thought the onset of symptoms and necrosis coincided: there is a considerable variation in time between coronary artery occlusion and subsequent myocardial necrosis, t This variation is considered to be related to pre-occlusive development of collateral flow3 T h i s delay between occlusion and necrosis could explain the low sensitivity of chemical tests investigated. T h e authors emphasise that "in 40--60% of patients E C G signs are absent or inconclusive". It is true that the sensitivity of a single E C G at admission is limited: S T - s e g m e n t elevation can be found within 3, 6, 12, 24 h after onset of chest pain in 28, 37, 41, 45% of patients with subsequently confirmed M I . 3 Continuous ST-segment monitoring of acutely ischaemie myocardial regions identified by standard 12-lead E C G s recorded during the presenting chest pain is a sensitive method of assessing alterations in myocardial perfusion? Continuous ST-segment monitoring has a further benefit over chemical tests: the latter reflects the development of irreversible myocardial damage (ie, necrosis), while continuous S T segment monitoring reflects perfusion of myocardium not immediately resulting in necrosis. Therefore ST-segment monitoring allows intervention far earlier and the achievement of better results. II Departmentof Internal Medicine, St George's Hospital, Sz6kestch&v8r8000, SeregE$1yesiSt 1, Hungary
1 Tiefenbrunn AJ, Sobel BE. Timing of coronary recanalisation, paradigms, paradoxes, and pertinence. Circulation 1992', 85: 2311-15. 2 Patterson DLH, Treasure T. The culprit coronary artery lesion. Lancet 1991; 938: 1379-80. 3 Karlson BW, Herlitz J, Evardsson N, et al. Eligibility for intravenous thrombolysis in suspected acute myocardial infarction. Circulation 1990; 82: 1140--46. 4 Shah PK, Cercek B, Law AS, Ganz W. Angiographic validation of bedside markers of reperfusion..7 A m Coil Cardio11993; 21: 55-61.
Vo1342 • December 18/25, 1993
AMI (n=,15)
thresholds required to rule-in or rule-out such a diagnosis are different. 2 Third, the rule-out decision threshold varies with the time after the onset of symptoms? Finally, combination testing--ie, testing in series or parallel m o d e - - c a n increase test sensitivity or specificity.3 None of these aspects appear to have been addressed in Bakker's study. Studies by others" and ourselves (unpublished) contradict Bakker's claim. Out results indicate that all these analytes are highly effective at time after the onset of symptoms earlier than Bakker's 10 h limit (table). We conclude that myoglobin is a useful early marker and that CK-2 (mass) and troponin T are later, but equally effective, markers for MI.
noAMI (n=69)
non~i~n~onAP AD delay
<3h/~3h
i
I
CKM/~mass
noacute acute is~hemia i~hcmia
~AMI
Vipin Bhayana,A Ralph Henderson
~6.7 >6.7
noAMI
AI~
Department of Clinical Biochemistry, UniversityHospital (Universityof Western Ontario), London,Ontario N6A 5A5, Canada
1 Leung FY, Galbraith LV, Jablonsky G, Henderson AR. Re-evaluation of the diagnostic utility of serum total creatine kinase and creatine kinase-2 in myocardial infarction. Clin Chem 1989; 35: 1435-40. 2 Leung FY, Griffith AP, Jahlonsky G, Henderson AR. Comparison of the diagnostic utility of timed serial (slope) creatine kinase measurements with conventional serum tests in the early diagnosis of myocardial infarction. Ann Clin Biochem 1991; 28= 78-82. 3 Cebul RD, Hershey JC, Williams SV. Using multiple tests: series and parallel approaches. Clin Lab M e d 1982; 2: 871-90. 4 Muir J, Armer-Dworzak E, Lechleimer P, et al. Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin. Br Heart ff 1992; 68: 462-68.
[AM]
ECG
A
no acute
acute
ischemia ischetnia
non-Qwave
Q v/ave
Figure: Binary decision tree for MI For ECG criteria required for the diagnosis "acute ischaemia" see text. The number of patients with Q wave MI fulfilling decision criteria is given in the upper left quarter, with nen-Q wave AMI in the lower left, with angina pectoris (AP) in the upper right, and with chest pain not related to coronary artery disease (non-CAD) in the lower right quarter of circles.
contingency table was 88"2 (95% CI 25-7-303"2, p < 0-0001). T h e decision tree established in this study can help to guide patients' care and should be prospectively evaluated by other hospitals. Johannes Mair Inatitut for Medizinische Chemie und Biochamie. Fritz-Preglstrasse 3, A-6020 fnnsbruck,Austria
World Health Organization criteria for the diagnosis of acute myocardial infarction. Proposal for the multinational monitoring of trends and determinants in cardiovascular disease. Geneva: WHO, Cardiovascular Disease Unit, 1981.
S I R - - T h e claim by Bakker and colleagues that t h e measurement of myoglobin, C K - 2 (mass), and troponin T do not allow exclusion of M I within 10 h has serious flaws. First, they use each test's upper reference limit without defining the population used for its derivation. We have shown that conventionally-derived ranges are inappropriate for diagnostic purposes in coronary care units. I Second, the decision Test
Rule-out deslskm threshold
'time(h)*
Kernel Simon
0-3
3-6
6-9
9-12
45 (80-St)
82 (68-91) 81 (46-75) 85 (40-69)
95 (N-88) 81 (81-97) 91 (91-97)
95 (M-t00) 98 (86-100) 98 (M-IO0)
(p/L) Myoglobln
74
CK.2(mass)
8.0
12
TmponlnT
0'1
(4-26) 24 (12-39)
Populationcomprised65 patie0tswith MI and 60 without. *Fromonsetof symptoms.
Table: Test sensltMtles of (95% CI) myoglobln, CK-2 (mass), and troponin T
1554
SIR--Bakker and colleagues found that even the newer markers (myoglobin, troponin T) and methods ( C K - M B mass concentration) have too low sensitivity and specificity in verificatibn of M I during the first 10 h after onset of chest pain. I do not suppose the authors thought the onset of symptoms and necrosis coincided: there is a considerable variation in time between coronary artery occlusion and subsequent myocardial necrosis, t This variation is considered to be related to pre-occlusive development of collateral flow3 T h i s delay between occlusion and necrosis could explain the low sensitivity of chemical tests investigated. T h e authors emphasise that "in 40--60% of patients E C G signs are absent or inconclusive". It is true that the sensitivity of a single E C G at admission is limited: S T - s e g m e n t elevation can be found within 3, 6, 12, 24 h after onset of chest pain in 28, 37, 41, 45% of patients with subsequently confirmed M I . 3 Continuous ST-segment monitoring of acutely ischaemie myocardial regions identified by standard 12-lead E C G s recorded during the presenting chest pain is a sensitive method of assessing alterations in myocardial perfusion? Continuous ST-segment monitoring has a further benefit over chemical tests: the latter reflects the development of irreversible myocardial damage (ie, necrosis), while continuous S T segment monitoring reflects perfusion of myocardium not immediately resulting in necrosis. Therefore ST-segment monitoring allows intervention far earlier and the achievement of better results. II Departmentof Internal Medicine, St George's Hospital, Sz6kestch&v8r8000, SeregE$1yesiSt 1, Hungary
1 Tiefenbrunn AJ, Sobel BE. Timing of coronary recanalisation, paradigms, paradoxes, and pertinence. Circulation 1992', 85: 2311-15. 2 Patterson DLH, Treasure T. The culprit coronary artery lesion. Lancet 1991; 938: 1379-80. 3 Karlson BW, Herlitz J, Evardsson N, et al. Eligibility for intravenous thrombolysis in suspected acute myocardial infarction. Circulation 1990; 82: 1140--46. 4 Shah PK, Cercek B, Law AS, Ganz W. Angiographic validation of bedside markers of reperfusion..7 A m Coil Cardio11993; 21: 55-61.
Vo1342 • December 18/25, 1993