Sunday, May 10, 2009
Even slight BP elevations linked to increased AF incidence among women
April 2009
MedWire News: Blood pressure (BP) is strongly associated with incident atrial fibrillation (AF) among initially healthy women, with the systolic a better predictor than the diastolic measure, findings from the Women’s Health Study show.
Furthermore, the study indicates that BP values below the current threshold for the diagnosis of arterial hypertension are significantly associated with the risk for incident AF.
“Even slightly elevated BP levels at baseline imposed some degree of increased risk,” write study authors David Conen (University Hospital Basel, Switzerland) and colleagues in the journal Circulation.
Because treatment of established AF has limited long-term success and is associated with significant risks, characterizing treatable risk factors for AF has “substantial clinical relevance” the team notes.
The researchers prospectively followed up 34,211 women for incident AF over 12.4 years, and then compared the incidence of AF across systolic and diastolic BP categories.
The women were aged 55 years on average at baseline; during follow-up, 644 had at least one confirmed episode of AF.
Analysis showed that both systolic and diastolic BP components were significantly and strongly associated with incident AF, after multivariable adjustment.
Even women with high-normal systolic (130 to 139 mm Hg) or diastolic (85 to 89 mm Hg) BP at baseline had 28% and 53% increased risks for incident AF compared with women with systolic BP <120 mm Hg or diastolic BP <65 mm Hg, respectively.
In further continuous and combined hazard modeling, systolic BP remained significantly and strongly positively associated with AF incidence, whereas diastolic BP did not.
Of note, say Conen and co-workers, models incorporating BP measures updated over time showed that women with systolic BP values between 130 and 139 mm Hg during follow-up also had a significantly increased risk for subsequent AF.
The team concludes: “Taken together, our findings indicate that tight BP control may help to reduce the growing burden of AF in the community.”
Circulation 2009; 119: 2146–2152
MedWire News: Blood pressure (BP) is strongly associated with incident atrial fibrillation (AF) among initially healthy women, with the systolic a better predictor than the diastolic measure, findings from the Women’s Health Study show.
Furthermore, the study indicates that BP values below the current threshold for the diagnosis of arterial hypertension are significantly associated with the risk for incident AF.
“Even slightly elevated BP levels at baseline imposed some degree of increased risk,” write study authors David Conen (University Hospital Basel, Switzerland) and colleagues in the journal Circulation.
Because treatment of established AF has limited long-term success and is associated with significant risks, characterizing treatable risk factors for AF has “substantial clinical relevance” the team notes.
The researchers prospectively followed up 34,211 women for incident AF over 12.4 years, and then compared the incidence of AF across systolic and diastolic BP categories.
The women were aged 55 years on average at baseline; during follow-up, 644 had at least one confirmed episode of AF.
Analysis showed that both systolic and diastolic BP components were significantly and strongly associated with incident AF, after multivariable adjustment.
Even women with high-normal systolic (130 to 139 mm Hg) or diastolic (85 to 89 mm Hg) BP at baseline had 28% and 53% increased risks for incident AF compared with women with systolic BP <120 mm Hg or diastolic BP <65 mm Hg, respectively.
In further continuous and combined hazard modeling, systolic BP remained significantly and strongly positively associated with AF incidence, whereas diastolic BP did not.
Of note, say Conen and co-workers, models incorporating BP measures updated over time showed that women with systolic BP values between 130 and 139 mm Hg during follow-up also had a significantly increased risk for subsequent AF.
The team concludes: “Taken together, our findings indicate that tight BP control may help to reduce the growing burden of AF in the community.”
Circulation 2009; 119: 2146–2152
Noncompliance ‘major cause of aspirin resistance’ in stented patients
May 2009
MedWire News: Aspirin resistance is rare in compliant patients receiving the drug for secondary cardiovascular disease prevention after coronary stenting, being mostly found in noncompliant patients who respond when therapy is controlled, reports a French team.
Thomas Cuisset (CHU Timone, Marseille, France) and colleagues prospectively followed-up 136 consecutive patients undergoing coronary stenting for compliance and aspirin response during hospitalization and at 1 month after hospital discharge. The patients’ aspirin responses were determined using the arachidonic acid-induced platelet aggregation (AA-Ag) assay performed on peripheral blood samples.
The researchers contend that, while several mechanisms have been put forward for the wide variability in antiplatelet therapy response, “the first reason to have inadequate platelet inhibition in patients treated with aspirin is noncompliance.” Thus they hypothesized that aspirin resistance would be rare when assessed by methods that directly measure inhibition of platelet cyclo-oxygenase (COX)-1 activity.
Their results showed that AA-Ag ranged from 0 to 34% during the inhospital phase, at a mean of 7.5%. Four (3%) patients were classed as nonresponders, defined as having AA-Ag >30%, although Cuisset and team note all four had post-treatment AA-Ag lower than 35%.
At 1 month postdischarge, however, AA-Ag ranged from 0 to 94%, with a significantly higher mean compared with the hospital phase, at 15.3% (p=0.004), and 19 (14%) patients were identified as nonresponders.
The 19 nonresponders received controlled intake of oral 75 mg aspirin and their response was reassessed. Only one patient remained a nonresponder.
The authors say a similar pattern was seen using the most common definition of aspirin nonresponse of AA-Ag >20%, with 12 nonresponders in hospital and 32 at 1 month, suggesting a further 18 noncompliant patients who were clearly identified as such following further investigation with the patients, families, and general practitioners. Nine claimed they simply forgot to take their medication, while the other nine stopped because of side effects, mainly gastrointestinal (seven patients) or minor bleeding (two patients).
“Noncompliance should be eliminated before treating with alternative and/or additional antiplatelet medications,” the team concludes in the American Heart Journal.
MedWire is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
Am Heart J 2009; 157: 889-893
MedWire News: Aspirin resistance is rare in compliant patients receiving the drug for secondary cardiovascular disease prevention after coronary stenting, being mostly found in noncompliant patients who respond when therapy is controlled, reports a French team.
Thomas Cuisset (CHU Timone, Marseille, France) and colleagues prospectively followed-up 136 consecutive patients undergoing coronary stenting for compliance and aspirin response during hospitalization and at 1 month after hospital discharge. The patients’ aspirin responses were determined using the arachidonic acid-induced platelet aggregation (AA-Ag) assay performed on peripheral blood samples.
The researchers contend that, while several mechanisms have been put forward for the wide variability in antiplatelet therapy response, “the first reason to have inadequate platelet inhibition in patients treated with aspirin is noncompliance.” Thus they hypothesized that aspirin resistance would be rare when assessed by methods that directly measure inhibition of platelet cyclo-oxygenase (COX)-1 activity.
Their results showed that AA-Ag ranged from 0 to 34% during the inhospital phase, at a mean of 7.5%. Four (3%) patients were classed as nonresponders, defined as having AA-Ag >30%, although Cuisset and team note all four had post-treatment AA-Ag lower than 35%.
At 1 month postdischarge, however, AA-Ag ranged from 0 to 94%, with a significantly higher mean compared with the hospital phase, at 15.3% (p=0.004), and 19 (14%) patients were identified as nonresponders.
The 19 nonresponders received controlled intake of oral 75 mg aspirin and their response was reassessed. Only one patient remained a nonresponder.
The authors say a similar pattern was seen using the most common definition of aspirin nonresponse of AA-Ag >20%, with 12 nonresponders in hospital and 32 at 1 month, suggesting a further 18 noncompliant patients who were clearly identified as such following further investigation with the patients, families, and general practitioners. Nine claimed they simply forgot to take their medication, while the other nine stopped because of side effects, mainly gastrointestinal (seven patients) or minor bleeding (two patients).
“Noncompliance should be eliminated before treating with alternative and/or additional antiplatelet medications,” the team concludes in the American Heart Journal.
MedWire is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
Am Heart J 2009; 157: 889-893
Sustained VT/VF linked to increased mortality after PCI in STEMI patients
6 May 2009
MedWire News: Patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who develop sustained ventricular fibrillation or tachycardia before or after the procedure have significantly increased 90-day mortality, a study reveals.
Rajendra Mehta (Duke Clinical Research Institute, Durham, North Carolina, USA) and team evaluated the association of ventricular fibrillation (VF) or ventricular tachycardia (VT) and its timing with risk for death at 30 and 90 days in 5745 patients with STEMI undergoing PCI at 296 hospitals in 17 countries.
They report in the Journal of the American Medical Association that VT/VF occurred in 329 (5.7%) patients. The majority of these occurred early (before the end of catheterization, n=205; 64%), and 90% occurred within 48 hours of presentation with STEMI symptoms.
The 90-day mortality rate was significantly higher among patients with any VT/VF compared with those without, at 23.2% versus 3.6%, and an adjusted hazard ratio (HR) of 3.63. Outcomes were particularly worsened among patients with late (after the end of catheterization) VT/VF, with a 90-day mortality of 33.3% (HR=5.59), although still significantly worse for those with early VT/VF,at 90-day mortality of 17.2% (HR=2.34).
Factors associated with late VT/VF were low systolic blood pressure, increased heart rate (>70 beats per minute) and body weight, ST resolution less than 70%, post-PCI Thrombolysis in MI (TIMI) flow below grade 3 and pre-PCI TIMI flow grade 0, and beta-blocker treatment for less than 24 hours.
“Our analysis identified patients who may benefit from closer surveillance int eh intensive care or telemetry unit after the PCI procedure because of the risk for late VT/VF,” the authors write.
“In contrast, because of very low risk for late VT/VF in patients with complete reperfusion, our findings suggest that close monitoring for late VT.VF may not be necessary and these patients may be candidates for early discharge.”
They add that, as most patients with STEMI worldwide are routinely moitored for longer than 72 hours, these findings have the potential to decrease resource use without compromising patient safety when a risk-based strategy of monitoring or early discharge is followed.
JAMA 2009; 301: 1779-1789
MedWire News: Patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who develop sustained ventricular fibrillation or tachycardia before or after the procedure have significantly increased 90-day mortality, a study reveals.
Rajendra Mehta (Duke Clinical Research Institute, Durham, North Carolina, USA) and team evaluated the association of ventricular fibrillation (VF) or ventricular tachycardia (VT) and its timing with risk for death at 30 and 90 days in 5745 patients with STEMI undergoing PCI at 296 hospitals in 17 countries.
They report in the Journal of the American Medical Association that VT/VF occurred in 329 (5.7%) patients. The majority of these occurred early (before the end of catheterization, n=205; 64%), and 90% occurred within 48 hours of presentation with STEMI symptoms.
The 90-day mortality rate was significantly higher among patients with any VT/VF compared with those without, at 23.2% versus 3.6%, and an adjusted hazard ratio (HR) of 3.63. Outcomes were particularly worsened among patients with late (after the end of catheterization) VT/VF, with a 90-day mortality of 33.3% (HR=5.59), although still significantly worse for those with early VT/VF,at 90-day mortality of 17.2% (HR=2.34).
Factors associated with late VT/VF were low systolic blood pressure, increased heart rate (>70 beats per minute) and body weight, ST resolution less than 70%, post-PCI Thrombolysis in MI (TIMI) flow below grade 3 and pre-PCI TIMI flow grade 0, and beta-blocker treatment for less than 24 hours.
“Our analysis identified patients who may benefit from closer surveillance int eh intensive care or telemetry unit after the PCI procedure because of the risk for late VT/VF,” the authors write.
“In contrast, because of very low risk for late VT/VF in patients with complete reperfusion, our findings suggest that close monitoring for late VT.VF may not be necessary and these patients may be candidates for early discharge.”
They add that, as most patients with STEMI worldwide are routinely moitored for longer than 72 hours, these findings have the potential to decrease resource use without compromising patient safety when a risk-based strategy of monitoring or early discharge is followed.
JAMA 2009; 301: 1779-1789
Saturday, May 9, 2009
Prediction of Early Complications in Patients With Acute Myocardial Infarction by Calculation of the ST Score
Prediction of Early Complications in Patients With Acute Myocardial Infarction by Calculation of the ST Score
Marianne Gwechenberger MD
Wolfgang Schreiber MD
Harald Kittler MD
Michael Binder MD
Bernhard Hohenberger
Anton N Laggner MD
Michael M Hirschl MD
Clinic of Internal Medicine II, Department of Cardiology Department of Emergency Medicine, University of Vienna, Vienna, Austria.
47/1/85428
Study objective:
To assess the relationship between the sum of ST-segment elevations (ST score) in the admission ECG and the occurrence of early complications in patients with acute myocardial infarction (MI).
Methods:
We conducted an observational study of patients who presented with acute anterior or inferior MI to the ED of a 2,000-bed inner-city hospital. Age, sex, time from onset of pain and the start of thrombolysis, and ST score were evaluated by the emergency physician. "Early complications" were defined as acute congestive heart failure or severe rhythm disturbances in the 24 hours after the start of thrombolysis. The outcome measures were the relationship between ST score and the occurrence of early complications; the influence of age, sex, or time between onset of pain and thrombolysis; and identification of a cutoff value with the highest sensitivity and specificity for prediction of complications.
Results:
We included 243 patients (194 men, 49 women; mean age, 56.6 years) with acute MI (anterior, 119; inferior, 124) who underwent thrombolysis in our analysis. ST score was significantly greater in patients with early complications, compared with patients without complications (anterior, 10.3 versus 19.4 mm [ P<.001]; inferior, 6.9 versus 10.4 mm [ P<.001]). Receiver-operator curve analysis revealed an ST score of 13 mm in patients with anterior MI and 9 mm in patients with inferior MI as the cutoff value with the greatest sensitivity and specificity for predicting early complications of MI. (For anterior MI, sensitivity was .79, specificity .73; for inferior MI, sensitivity was .64 and specificity .68.). On multivariate regression analysis, ST score was an independent predictor of the occurrence of at least one complication. (For anterior MI, the odds ratio [OR] was 9.7 and the 95% confidence interval [CI] 3.9 to 25.1; for inferior MI the OR was 5.0 and the 95% CI 2.0 to 12.8). Age, sex, and interval from onset of pain to treatment had no significant effect on the occurrence of early complications.
Conclusion:
The absolute ST score is useful in estimating the probability of early complications in patients with acute MI receiving
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thrombolytic therapy. A cutoff value of 13 mm for anterior MI and 9 mm for inferior MI stratifies patients into high- and low-risk subgroups for the development of acute congestive heart failure and severe rhythm disturbances during the first 24 hours of hospitalization.
[Gwechenberger M, Schreiber W, Kittler H, Binder M, Hohenberger B, Laggner A, Hirschl MM: Prediction of early complications in patients with acute myocardial infarction by calculation of the ST score. Ann Emerg Med November 1997;30:563-570.]
Received for publication February 28, 1997.
Revision received June 20, 1997.
Accepted for publication July 3, 1997.
Copyright © by the American College of Emergency Physicians.
Address for reprints:
Michael M Hirschl, MD
Department of Emergency Medicine
Wahringer Gurtel 18-20
A-1090 Vienna
Austria
43-1-40400-1964
Fax 43-1-40400-1965
E-mail michael.hirschl@akh-wien.ac.at
INTRODUCTION
The initial ECGs of patients admitted to the ED or CCU have been used to stratify patients into groups at low and high risk for the development of in-hospital life-threatening complications and death. [1] [2] [3] [4] [5] Whereas signs of myocardial infarction (MI), left bundle-branch block, and left ventricular hypertrophy on the initial ECG are associated with a high frequency of adverse events or the need for procedures, [6] normal ECG findings or an ECG with minimal changes indicate a low risk of further complications in patients with suspected MI. [7] In addition, it has been demonstrated that the presence of ST-segment elevation in lead V4R in patients with acute inferior MI is a strong and independent predictor of major complications. [8] [9]
In the last 10 years, thrombolytic therapy has become an important therapeutic tool in patients with acute MI, as survival of patients with acute MI has markedly improved as a result of thrombolysis. [10] [11] However, especially in the early phase after acute MI (within 24 hours of the onset of pain), acute complications including congestive heart failure or rhythm disturbances are commonly observed. Easily available markers for the prediction of these complications would be helpful in stratifying patients with acute MI undergoing thrombolysis into high- and low-risk groups at the time of admission to the ED or CCU. Birnbaum et al [12] demonstrated that different patterns of ST-segment changes in the initial ECG are associated with different prognoses in patients who have sustained acute MI. In contrast to the assessment of the initial ECG pattern, the amount of ST-segment elevation (ST score) seems a more easily available parameter for the treating physician in the ED or CCU. [13] The predictive value of the ST score for early complications in patients with acute MI undergoing thrombolytic therapy has not been investigated until now. We therefore designed a study to assess (1) the relationship between ST score on the admission ECG and occurrence of early complications and (2) the influence of other factors (eg, interval from onset of pain to treatment, age, sex) on this relationship in patients with acute MI undergoing thrombolytic therapy.
MATERIALS AND METHODS
We conducted this study in the ED of the General Hospital (Vienna, Austria) between January 1, 1994, and December 31, 1996. Data from all patients who were admitted to the ED with evidence of an acute MI and given thrombolytic therapy were prospectively collected.
The study protocol was renewed by the local institutional review board and found to be in accordance with the ethical standards of the review board and with the Helsinki Declaration of 1975, as revised in 1983.
In this study we sought to evaluate the relationship between ST score on the admission ECG and the occurrence of early complications and the influence of other factors (eg, interval between the onset of pain and treatment, age, and sex) on this relationship in patients with acute MI who were undergoing thrombolytic therapy.
All patients with suspected MI (eg, chest pain of >30 minutes' duration, persistent ST-segment elevation in two or more anterior or inferior leads on the admission ECG) who were undergoing thrombolytic therapy were eligible for study. Consecutive ECGs and serial creatine kinase-MB (CK-MB) determinations were performed to confirm the diagnosis of acute MI (ie, evidence of new Q waves in serial ECGs, a typical increase and decrease (or both) of the CK-MB concentration in the first 24 hours after ED admission).
Patients in whom Q waves did not develop (.04 seconds or longer) and those in whom the typical increase and decrease in CK-MB concentration did not appear were excluded from further analysis. Patients with evidence of early complications on admission (eg, acute congestive heart failure on the initial chest radiograph or severe rhythm disturbances on the initial ECG) were also dismissed from analysis.
In summary, the inclusion criteria for the study were evidence of acute MI, treatment with a thrombolytic agent, and no signs of early complications at the time of ED admission.
After admission, each patient received thrombolytic treatment with 100 mg recombinant tissue plasminogen activator (rtPA) in accordance with an accelerated front-loading scheme published by Neuhaus et al. [11] Treatment was preceded with an intravenous bolus of 5,000 IU conventional heparin and an oral 100-mg dose of aspirin. beta-Blockers and nitrates were given as deemed clinically appropriate.
Standard 12-lead electrocardiographic tracings were performed immediately after admission. The records were made at a paper speed of 25 mm/second and standardization at 1.0 mV to 1.0 cm. Infarct location was determined
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on admission, and patients were classified a priori as having anterior MI (ST-segment elevation in leads V1 through V6) or inferior MI (ST segment elevation in leads II, III, and aVF). A small proportion of patients exhibited ST-segment elevation in both anterior (V1 through V6, I, aVL) and inferior leads (II, III, aVF, V5, V6). These patients were classified as having anterior or inferior MI depending on whether the anterior or the inferior site had the greatest ST score. [14] ST-segment elevation was measured to the nearest .5 mm at the J point and summed for all leads but aVR. [14] [15] ST-segment elevation was considered significant if it was more than .1 mm from the baseline. ST-segment depression as observed in patients with posterior AMI as well as elevations in the right ventricular leads were not included in the analysis. Evaluation of the ECG also included the assessment of the number of leads involved and the extent of ST-segment elevation divided by the number of leads involved (ST score/ number of leads with ST-segment elevation).
The ECGs were generally analyzed by the emergency physician on duty. Reevaluation was conducted by two experienced emergency physicians (MMH, WS), blinded to all clinical data. The ST scores measured by all three physicians were averaged and used for analysis. In the case of a marked difference between the physician (ie, >2 mm difference), the ECG was reanalyzed by all three emergency physicians together in an attempt to reach a consensus. The interobserver variability was 96%.
Patients with evidence of acute congestive heart failure on admission or severe rhythm disturbances at the time of the initial ECG were excluded from analysis.
Acute congestive heart failure was defined as evidence of bibasilar rales over the lungs that did not clear with coughing, a third-sound gallop over the heart and signs of congestion in one of the subsequent chest radiographs routinely performed 12 and 24 hours after ED admission. Radiographic signs of acute congestive heart failure were central or perihilar infiltrates, increased size of vessels serving the upper portions of the lungs in the upright position, and increased prominence of interlobular septa (usually bilateral and symmetric).
Severe rhythm disturbances included bradyarrhythmias (asystole, type 2 second-degree or third-degree atrioventricular block, bradycardia associated with hypotension [systolic blood pressure <90 mm Hg] requiring atropine or insertion of a temporary pacemaker), and tachyarrhythmias (ventricular fibrillation, ventricular tachycardia requiring electrical or chemical cardioversion, rapid atrial fibrillation associated with hypotension [systolic blood pressure <90 mm Hg] requiring digitalis or amiodarone).
All patients who died during the 24 hours after admission to the ED were noted.
We retrieved the following data from the ED charts: age, sex, duration of chest pain, peak creatine kinase (CK) and CK-MB, and complications noted during the 24 hours after ED admission. ST score was calculated according to the previously noted criteria. On the basis of these data, we established a model to predict the appearance of early complications according to the extent of the ST score in the admission ECG.
The following parameters were classified as independent variables in the model: age, sex, interval between onset of pain and the start of thrombolytic therapy, and the calculated sum of ST-segment elevation in the admission ECG.
Evidence of acute congestive heart failure or severe rhythm disturbances in the 24 hours after ED admission were the dependent or outcome variables in this model. Cutoff points were identified for the greatest sensitivity or specificity for the prediction of early complications. The influence of time from onset of pain to treatment, age, and sex was evaluated with the use of a multivariate regression analysis.
Diagnostic performance was described in terms of areas under the receiver-operator curves (ROCs) in accordance with the methods described previously. [16] [17] [18] The ROC analysis software of Centor and Keightley (Blue Ridge Express) was used to obtain area calculations.
We described continuous data with the mean and SD or median and interquartile range (IQR) as appropriate. We used the unpaired Student t test or the nonparametric Mann-Whitney U test for the comparison of groups and the chi2 test for comparisons of proportions. Logistic-regression analysis was used for the estimation of odds ratios (ORs). Numeric values were rounded to the nearest integer. Two-tailed P values less than .05 were considered statistically significant.
TABLE 1 -- General data. Features Anterior MI Inferior MI P
No. of patients 119 124
Age (yr) [mean±SD] 57.1±12.2 56.2±11.5 NS
Sex (M/F) 98/21 96/28 NS
Median peak CK
value (U/L) [IQR] 1,221 (502-1,980) 724 (399-1,115) .006
Median peak CK-MB
value (U/L) [IQR] 120 (72-194) 85 (45-130) .004
ST score (mm)
[mean±SD] 14.4±9.9 8.3±4.6 <.001
Median time to therapy
(min) [IQR] 110 (75-175) 110 (85-218) NS
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RESULTS
We included 243 patients (194 men, 49 women) with a mean±SD age of 56.6±11.8 years in the study (Table 1) . On the basis of electrocardiographic data, MI was located in the anterior wall in 119 patients and in the inferior wall in 124. Peak CK and CK-MB values were significantly greater in patients with anterior-wall infarction compared with those who had sustained inferior-wall infarctions (CK: 1,221 versus 724 U/L, P=.006; CK-MB: 120 versus 85 U/L, P=.004). Overall, in 103 patients (anterior MI: n=53; inferior MI: n=50; NS) either acute congestive heart failure (anterior MI: n=30; inferior MI: n=16; P=.03) or a rhythm disturbance (anterior MI: n=23; inferior MI: n=34; NS) was observed. The median interval from onset of pain to start of thrombolytic therapy was equal in patients with anterior and inferior MI (anterior MI: 110 minutes, IQR=75 to 175; inferior MI: 110 minutes, IQR=85 to 218; NS). Three patients died in the 24 hours after ED admission (anterior MI: n=2; inferior MI: n=1). Causes of death were cardiogenic shock (n=2) and left ventricular rupture (n=1).
In patients with evidence of complications, the sum of ST-segment elevation was significantly higher compared with
Figure 1. ROC curve showing the performance of ST score with regard to the prediction of early complications in patients with anterior MI.
that of patients without complications. This difference was observed in patients with anterior and inferior myocardial infarction (anterior MI: 10.3 versus 19.4 mm, P<.001; inferior MI: 6.9 versus 10.4 mm; P<.001). No significant differences were observed between patients with congestive heart failure and those with rhythm disturbances (anterior MI: 18.7 versus 15.9 mm, P=.42; inferior MI: 10.1 versus 9.5 mm; NS). The mean±SD ST score for the patients who died during the first 24 hours was 21.3±4.6 mm.
The number of leads with ST-segment elevation was significantly higher in patients with anterior MI and early complications than in those without serious events (4.2±1.2 versus 5.7±1.8, P<.05). In patients with inferior MI no significant difference was observed (3.3±.9 versus 3.4±.9, NS). The ST score divided by the number of leads with ST-segment elevation revealed a significantly higher score in patients with early complications compared with those without complications (anterior MI: 2.3±1.3 versus 3.6±1.9 mm/lead, P<.001; inferior MI: 1.9±.9 versus 3.0±1.4 mm/lead, P<.001). ROC curves show the performance of admission ST score in predicting early complications in anterior MI (Figure 1) . The mean±SD area under the curve is .80±.04. The optimal cutoff point maximizing sensitivity and specificity was found
Figure 2. ROC curve showing the performance of ST score with regard to the prediction of early complications in patients with inferior MI.
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at 13 mm, for a sensitivity of 79% and a specificity of 73%. The relative risk (RR) was significantly greater in patients above the cutoff value than in those below the cutoff (RR, 2.98; 95% confidence interval [CI], 1.9 to 4.8).
ROC curves show the performance of ST score on admission by early complications in inferior MI (Figure 2) . The mean±SD area under the curve was .72±.05. The optimal cutoff point was found at 9 mm, for a sensitivity of 64% and specificity of 68%. The RR is significantly greater in patients above the cutoff value compared with those below the cutoff value (RR, 2.1; IQR, 1.4 to 3.2).
With the cutoff values derived from ROC analysis, logistic-regression analysis showed that the admission ST score on admission was an independent predictor of the occurrence of early complications in patients with anterior MI (OR, 9.7; 95% CI, 3.9 to 25.1; P<.0001) and in patients with inferior MI (OR, 5.0; 95% CI, 2.0 to 12.8; P=.0002) (Table 2 , Figure 3) . An increase of 1.0 mm in ST score increases the odds of complications by 1.1 (95% CI, 1.1 to 1.2) for anterior MI and by 1.2 (95% CI, 1.1 to 1.4) for inferior MI. No other clinical variables available at the time of ED presentation were significantly associated with the occurrence of early complications in patients with anterior or inferior MI.
DISCUSSION
The initial ECG is frequently used to predict acute MI, serious complications and in-hospital mortality. [1] [2] [3] These studies were designed mainly to identify patients at high risk for a subsequent MI. [1] [2] [3] [4] [5] [6] Therefore patients with suspected acute MI were classified into high- and low-risk groups on the
TABLE 2 -- Multivariate analysis for the occurrence of early complications.
Anterior MI (n=119) Inferior MI (n=124)
Features OR (95% CI) P OR (95% CI) P
Age (yr)
70 1.0 NS 1.0 NS
>70 1.36 (.24-7.45)
.53 (.14-1.8)
Sex .84 (.22-3.29) NS .52 (.18-1.45) NS
Time to therapy
(min)
120 1.0 NS 1.0 NS
>120 1.46 (.55-3.99)
1.45 (.6-3.55)
ST score (mm)
13 1.0 <.0001
>13 9.73 (3.94-25.1)
9
1.0 .0002
>9
4.98 (2.04-12.84)
basis of evidence or absence of specific electrocardiographic patterns (eg, ST-segment elevation, left bundle-branch block, left ventricular hypertrophy, ST-segment depression). [1] Brush et al [1] demonstrated that patients with such "positive" admission-ECG findings had a significantly greater risk of a subsequent acute MI, serious complications or death than those with "negative" ECG findings. Also, patients with minimally abnormal admission ECG findings had a low risk of subsequent MI. [7]
In contrast, our study included patients with evidence of acute MI and was initiated to separate MI patients into those at high and low risk for subsequent complications in the 24 hours after admission on the basis of the ST score. In our series of 243 patients, the ST score was a good predictor of early complications during the 24 hours after acute MI; the ST score was significantly higher in patients with evidence of early complications compared with those without any events. This difference was observed in patients with anterior and inferior Mis, indicating that the ST score can be used independent of the infarct location. We also identified cutoff values of the ST score to calculate the risk for the occurrence of early complications. If the sum of the ST-segment elevations was greater than these cutoff values, the odds of early complications were 10 times greater in patients with anterior MI and five times greater in patients with inferior MI (Figure 3) . Other factors--age, sex, and time between onset of pain and thrombolysis--had no effect on the occurrence of early complications. Therefore ST
Figure 3. Schematic representation of the frequency of early complications in patients with anterior or inferior myocardial infarction according to the magnitude of the ST score on the admission ECG.
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score remains the only predictor of the occurrence of early complications in patients with acute MI.
The extent of the ST score is determined by the total number of leads and by the extent of ST-segment elevation in each lead with ST-segment changes. A higher ST score, therefore, can be due to an increase in the total number of leads with ST-segment elevation, an increase in the extent of ST-segment elevation in each lead, or both.
In patients with anterior MI and early complications increased ST score is caused not only by greater ST-segment elevation in each lead but by a higher total number of leads with ST-segment elevations. Therefore ST score may reflect the area of endangered myocardium in patients with anterior MI. Our data are in line with the findings of previously published reports demonstrating a relationship between ST score and infarct size. [19] [20] These reports also showed a correlation between the amount of ST-segment elevation and serious complications or death. [4] [21] [22] Figueras [4] et al reported a significant relationship between high ST-segment elevation and left ventricular rupture in patients with acute inferior MI. [4] Nielsen et al [21] demonstrated that "major ST elevations" were associated with a higher risk of fatal events compared with the patients with "minor ST elevations." These data are confirmed by our findings; the three patients who died in the first 24 hours were characterized by above-average ST scores (mean, 21.3 mm).
In contrast, the higher ST score in patients with inferior MI and early complications is caused by a greater ST-segment elevation in each affected lead; the total number of leads involved was similar in patients with and without early complications. Therefore, in patients with inferior MI, ST score only partially reflects the area of endangered myocardium.
Because ST-segment depressions are frequently observed in patients with inferior MI, [23] the exclusion of ST-segment depressions from ST-score calculation seems to be responsible for the lack of correlation between the area of endangered myocardium and ST score in patients with inferior MI. The calculation of the ST score without ST-segment depressions also contributes to the significant difference in the cutoff values between patients with anterior and inferior MI (9 mm versus 13 mm). However, ST-segment depression may be due to many nonischemic and chronic conditions (eg, left ventricular hypertrophy, treatment with digoxin or digitoxin, bundle-branch block) that may interfere with the acute ST-segment depressions caused by myocardial ischemia. Therefore inclusion of ST-segment depressions in such patients may lead to an increased ST score, resulting in decreased specificity. Currently the ST-scoring system is not suitable for patients with posterior infarction; these patients mainly exhibit ST-segment depressions. Further studies are required to evaluate the effect of the inclusion of ST-segment depressions in the ST score on sensitivity and specificity of our cutoff values in patients with inferior MI.
It must be emphasized that the results of our study are restricted to patients undergoing thrombolysis. The interval between onset of pain and treatment ranged from a minimum of 30 minutes to a maximum of 6 hours. It must also be emphasized that this interval may be too small to have any influence on the relationship between ST score and early complications. Whether longer intervals (eg, 6 to 12 hours between the onset of pain and the start of treatment) have any influence on the occurrence of early complications cannot be answered with our data. Also, the association between the area of endangered myocardium and the extent of ST score may be weak, especially in patients with inferior MI. Other methods such as echocardiography, scintigraphy or even biochemical markers may provide more accurate data about the area of endangered myocardium or infarct size. [24] [25] [26] [27] [28] Therefore these methods may be used to predict early complications more precisely than may the ST score. However, these methods require technical or laboratory skills, which may not be available in all EDs on a 24-hour basis. Additionally, none of these parameters is as easily available at the time of admission as the ST score.
Despite these limitations, our data have important clinical implications in the treatment of patients with acute MI. First, evaluation of the ST score on the initial ECG provides a simple method with which to identify patients at high risk for early complications. It follows that the patient at risk for complications may be transferred to an intermediate care unit with telemetric monitoring and trained nursing personnel. This procedure may save costs without compromising patient care. Second, patients at high risk of complications may be considered for a more aggressive therapeutic approach (eg, angioplasty or coronary artery bypass grafting) to reduce the risk of severe early complications.
In conclusion, the absolute ST score is useful in estimating the probability of early complications in patients with acute MI receiving thrombolytic therapy. A cutoff value of 13 mm for anterior MI and 9 mm for inferior MI risk-stratifies patients into high- and low-risk subgroups for development of acute congestive heart failure and severe rhythm disturbances during the first 24 hours of hospitalization. We therefore assume that the calculation of ST-segment elevation score on the admission ECG is clinically relevant because patients with acute MI may be classified as being at high or low risk shortly after ED admission. This stratification may have an important effect on the further treatment of the patient.
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REFERENCES
1. Brush JE, Brand DA, Acampora D, et al.: Use of the initial electrocardiogram to predict inhospital complications of acute myocardial infarction. N Engl J Med 1985;312:1137-1141.
2. Fesmire FM, Percy RF, Wean RL, et al: Risk stratification according to the initial electrocardiogram in patients with suspected acute myocardial infarction. Arch Intern Med 1989;149:1294-1297.
3. Young MJ, McMahon LF, Stross JK: Prediction rules for patients with suspected myocardial infarction: Applying guidelines in community hospitals. Arch Intern Med 1989;147:1219-1222.
4. Figueras J, Curos A, Cortadellas J, et al: Relevance of electrocardiographic findings, heart failure, and infarct site in assessing risk and timing of left ventricular free wall rupture during acute myocardial infarction. Am J Cardiol 1995;76:543-547.
5. Zalenski RJ, Sloan EP, Chen EH, et al: The ED ECG and immediately life-threatening complications in initially uncomplicated suspected myocardial ischemia. Ann Emerg Med 1988;17:221-226.
6. Stark ME, Vacek JL: The initial electrocardiogram during admission for myocardial infarction: Use as a predictor of clinical course and facility utilization. Arch Intern Med 1987;147:843-846.
7. Slater DK, Hlatky MA, Mark DB, et al: Outcome in suspected acute myocardial infarction with normal or minimally abnormal admission electrocardiographic findings. Am J Cardiol 1987;60: 766-770.
8. Zehender M, Kasper W, Kauder E, et al: Right ventricular infarction as an independent predictor of prognosis after inferior myocardial infarction. N Engl J Med 1993;328:981-988.
9. Zehender M, Kasper W, Kauder E, et al: Eligibility for and benefit of thrombolytic therapy in inferior myocardial infarction: Focus on the prognostic importance of right ventricular infarction. J Am Coll Cardiol 1994;24:362-369.
10. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group: ISIS-4: A randomized factorial trial assessing early captopril, oral mononitrate, and intravenous magnesium sulphate in 58.050 patients with suspected acute myocardial infarction. Lancet 1995;345:669- 685.
11. Neuhaus KL, von Essen R, Tebbe U, et al: Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: Results of the rt-Pa-APSAC patency study (TAPS). J Am Coll Cardiol 1992;19:892-893.
12. Birnbaum Y, Scamvsky S, Blum A, et al: Prognostic significance of the initial electrocardiographic pattern in a first acute anterior wall myocardial infarction. Chest 1993;103:1681-1687.
13. Wellens HJJ, Conover MB: The ECG in Emergency Decision Making, ed 1. Philadelphia: WB Saunders, 1992:1-26.
14. Clemmensen P, Grande P, Saunamaki K, et al: Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts. J Am Coll Cardiol 1990;5:1252-1257.
15. Aldrich HR, Wagner NB, Boswick J, et al: Use of initial ST segment deviation for prediction of final electrocardiographic size of acute myocardial infarcts. Am J Cardiol 1988;61:749-753.
16. Swets JA: Measuring the accuracy of diagnostic systems. Science 1988;240:1285-1293.
17. Centor RM: Signal detectability: The use of ROC curves and their analyses. Med Decis Making 1991;11:102-106.
18. Metz CE: ROC methodology in radiologic imaging. Invest Radiol 1986;21:720-733.
19. Mamko PR, Libby P, Covell JW, et al: Precordial ST segment elevation mapping: An atraumatic method for assessing alterations in the extent of myocardial injury: The effect of pharmacologic and hemodynamic interventions. Am J Cardiol 1972;29:223-230.
20. Muller JE, Maroko PR, Braunwald E: Evaluation of precordial mapping as a means of assessing changes in myocardial ischemic injury. Circulation 1975:52:16-27.
21. Nielsen BL: ST segment elevation in acute myocardial infarction: Prognostic importance. Circulation 1973;48:338-345.
22. Mauri F, Gasparini M, Barbonaglia L, et al: Prognostic significance of the extent of myocardial injury in acute myocardial infarction treated by streptokinase (the GISSI trial). Am J Cardiol 1989; 63:1291-1295.
23. Bates ER, Clemmensen PM, Califf RM, et al: Precordial ST-segment depression predicts a worse prognosis in inferior infarction despite reperfusion therapy. J Am Coll Cardiol 1990;16: 1538-1544.
24. Bonow RO, Dilsizian V, Cuocolo A, et al: Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction: Comparison of thallium scintigraphy with reinjection and PET imaging with 18 F-fluorodeoxyglucose. Circulation 1991;83:26-37.
25. Schiller N, Shah P, Crawford M, et al: American Society of Echocardiography Committee on Standards, Subcommittee on Quantification of Two-Dimensional Echocardiograms. J Am Soc Echo 1989;2:358-367.
26. Iliceto S, Marangelli V, Marchese A, et al: Myocardial contrast echocardiography in acute myocardial infarction: Pathophysiological background and clinical applications. Eur Heart J 1996;17:344-353.
27. Hamm CW, Katus HA: New biochemical markers for myocardial cell injury. Curr Opin Cardiol 1995;10:355-360.
28. Hirschl MM, Gwechenberger M, Binder T, et al: Assessment of myocardial injury by serum tumour necrosis factor alpha measurements in acute myocardial infarction. Eur Heart J 1996;17:1852-1859.
APPENDIX
TABLE 3 -- Sensitivity and specificity of different cutoff values in patients with anterior MI Cutoff Value
(ST Score [mm]) Sensitivity Specificity
51 .00 .98
50 .02 .98
42 .04 .97
38 .06 .97
31 .08 .97
30 .13 .97
29 .17 .97
28 .19 .97
27 .23 .97
26 .25 .97
25 .26 .95
24 .32 .95
23 .38 .95
22 .40 .95
21 .45 .95
20 .45 .92
19 .51 .91
18 .53 .89
17 .55 .86
16 .55 .83
15 .60 .82
14 .72 .79
13 .79 .73
12 .79 .68
11 .85 .65
10 .87 .56
9 .87 .50
8 .89 .35
7 .94 .32
6 .96 .27
5 1.00 .23
4 1.00 .15
3 1.00 .08
2 1.00 .02
0 1.00 .00
TABLE 4 -- Sensitivity and specificity of different cutoff values in patients with inferior MI Cutoff Value
(ST Score [mm]) Sensitivity Specificity
30 .02 1.00
21 .02 .99
18 .06 .97
17 .06 .96
16 .08 .96
15 .16 .95
14 .24 .93
13 .30 .93
12 .40 .93
11 .54 .86
10 .56 .80
9 .64 .68
8 .70 .58
7 .78 .53
6 .86 .41
5 .90 .32
4 .96 .22
3 .96 .07
2 .98 .00
1 1.00 .00
Em
Marianne Gwechenberger MD
Wolfgang Schreiber MD
Harald Kittler MD
Michael Binder MD
Bernhard Hohenberger
Anton N Laggner MD
Michael M Hirschl MD
Clinic of Internal Medicine II, Department of Cardiology Department of Emergency Medicine, University of Vienna, Vienna, Austria.
47/1/85428
Study objective:
To assess the relationship between the sum of ST-segment elevations (ST score) in the admission ECG and the occurrence of early complications in patients with acute myocardial infarction (MI).
Methods:
We conducted an observational study of patients who presented with acute anterior or inferior MI to the ED of a 2,000-bed inner-city hospital. Age, sex, time from onset of pain and the start of thrombolysis, and ST score were evaluated by the emergency physician. "Early complications" were defined as acute congestive heart failure or severe rhythm disturbances in the 24 hours after the start of thrombolysis. The outcome measures were the relationship between ST score and the occurrence of early complications; the influence of age, sex, or time between onset of pain and thrombolysis; and identification of a cutoff value with the highest sensitivity and specificity for prediction of complications.
Results:
We included 243 patients (194 men, 49 women; mean age, 56.6 years) with acute MI (anterior, 119; inferior, 124) who underwent thrombolysis in our analysis. ST score was significantly greater in patients with early complications, compared with patients without complications (anterior, 10.3 versus 19.4 mm [ P<.001]; inferior, 6.9 versus 10.4 mm [ P<.001]). Receiver-operator curve analysis revealed an ST score of 13 mm in patients with anterior MI and 9 mm in patients with inferior MI as the cutoff value with the greatest sensitivity and specificity for predicting early complications of MI. (For anterior MI, sensitivity was .79, specificity .73; for inferior MI, sensitivity was .64 and specificity .68.). On multivariate regression analysis, ST score was an independent predictor of the occurrence of at least one complication. (For anterior MI, the odds ratio [OR] was 9.7 and the 95% confidence interval [CI] 3.9 to 25.1; for inferior MI the OR was 5.0 and the 95% CI 2.0 to 12.8). Age, sex, and interval from onset of pain to treatment had no significant effect on the occurrence of early complications.
Conclusion:
The absolute ST score is useful in estimating the probability of early complications in patients with acute MI receiving
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thrombolytic therapy. A cutoff value of 13 mm for anterior MI and 9 mm for inferior MI stratifies patients into high- and low-risk subgroups for the development of acute congestive heart failure and severe rhythm disturbances during the first 24 hours of hospitalization.
[Gwechenberger M, Schreiber W, Kittler H, Binder M, Hohenberger B, Laggner A, Hirschl MM: Prediction of early complications in patients with acute myocardial infarction by calculation of the ST score. Ann Emerg Med November 1997;30:563-570.]
Received for publication February 28, 1997.
Revision received June 20, 1997.
Accepted for publication July 3, 1997.
Copyright © by the American College of Emergency Physicians.
Address for reprints:
Michael M Hirschl, MD
Department of Emergency Medicine
Wahringer Gurtel 18-20
A-1090 Vienna
Austria
43-1-40400-1964
Fax 43-1-40400-1965
E-mail michael.hirschl@akh-wien.ac.at
INTRODUCTION
The initial ECGs of patients admitted to the ED or CCU have been used to stratify patients into groups at low and high risk for the development of in-hospital life-threatening complications and death. [1] [2] [3] [4] [5] Whereas signs of myocardial infarction (MI), left bundle-branch block, and left ventricular hypertrophy on the initial ECG are associated with a high frequency of adverse events or the need for procedures, [6] normal ECG findings or an ECG with minimal changes indicate a low risk of further complications in patients with suspected MI. [7] In addition, it has been demonstrated that the presence of ST-segment elevation in lead V4R in patients with acute inferior MI is a strong and independent predictor of major complications. [8] [9]
In the last 10 years, thrombolytic therapy has become an important therapeutic tool in patients with acute MI, as survival of patients with acute MI has markedly improved as a result of thrombolysis. [10] [11] However, especially in the early phase after acute MI (within 24 hours of the onset of pain), acute complications including congestive heart failure or rhythm disturbances are commonly observed. Easily available markers for the prediction of these complications would be helpful in stratifying patients with acute MI undergoing thrombolysis into high- and low-risk groups at the time of admission to the ED or CCU. Birnbaum et al [12] demonstrated that different patterns of ST-segment changes in the initial ECG are associated with different prognoses in patients who have sustained acute MI. In contrast to the assessment of the initial ECG pattern, the amount of ST-segment elevation (ST score) seems a more easily available parameter for the treating physician in the ED or CCU. [13] The predictive value of the ST score for early complications in patients with acute MI undergoing thrombolytic therapy has not been investigated until now. We therefore designed a study to assess (1) the relationship between ST score on the admission ECG and occurrence of early complications and (2) the influence of other factors (eg, interval from onset of pain to treatment, age, sex) on this relationship in patients with acute MI undergoing thrombolytic therapy.
MATERIALS AND METHODS
We conducted this study in the ED of the General Hospital (Vienna, Austria) between January 1, 1994, and December 31, 1996. Data from all patients who were admitted to the ED with evidence of an acute MI and given thrombolytic therapy were prospectively collected.
The study protocol was renewed by the local institutional review board and found to be in accordance with the ethical standards of the review board and with the Helsinki Declaration of 1975, as revised in 1983.
In this study we sought to evaluate the relationship between ST score on the admission ECG and the occurrence of early complications and the influence of other factors (eg, interval between the onset of pain and treatment, age, and sex) on this relationship in patients with acute MI who were undergoing thrombolytic therapy.
All patients with suspected MI (eg, chest pain of >30 minutes' duration, persistent ST-segment elevation in two or more anterior or inferior leads on the admission ECG) who were undergoing thrombolytic therapy were eligible for study. Consecutive ECGs and serial creatine kinase-MB (CK-MB) determinations were performed to confirm the diagnosis of acute MI (ie, evidence of new Q waves in serial ECGs, a typical increase and decrease (or both) of the CK-MB concentration in the first 24 hours after ED admission).
Patients in whom Q waves did not develop (.04 seconds or longer) and those in whom the typical increase and decrease in CK-MB concentration did not appear were excluded from further analysis. Patients with evidence of early complications on admission (eg, acute congestive heart failure on the initial chest radiograph or severe rhythm disturbances on the initial ECG) were also dismissed from analysis.
In summary, the inclusion criteria for the study were evidence of acute MI, treatment with a thrombolytic agent, and no signs of early complications at the time of ED admission.
After admission, each patient received thrombolytic treatment with 100 mg recombinant tissue plasminogen activator (rtPA) in accordance with an accelerated front-loading scheme published by Neuhaus et al. [11] Treatment was preceded with an intravenous bolus of 5,000 IU conventional heparin and an oral 100-mg dose of aspirin. beta-Blockers and nitrates were given as deemed clinically appropriate.
Standard 12-lead electrocardiographic tracings were performed immediately after admission. The records were made at a paper speed of 25 mm/second and standardization at 1.0 mV to 1.0 cm. Infarct location was determined
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on admission, and patients were classified a priori as having anterior MI (ST-segment elevation in leads V1 through V6) or inferior MI (ST segment elevation in leads II, III, and aVF). A small proportion of patients exhibited ST-segment elevation in both anterior (V1 through V6, I, aVL) and inferior leads (II, III, aVF, V5, V6). These patients were classified as having anterior or inferior MI depending on whether the anterior or the inferior site had the greatest ST score. [14] ST-segment elevation was measured to the nearest .5 mm at the J point and summed for all leads but aVR. [14] [15] ST-segment elevation was considered significant if it was more than .1 mm from the baseline. ST-segment depression as observed in patients with posterior AMI as well as elevations in the right ventricular leads were not included in the analysis. Evaluation of the ECG also included the assessment of the number of leads involved and the extent of ST-segment elevation divided by the number of leads involved (ST score/ number of leads with ST-segment elevation).
The ECGs were generally analyzed by the emergency physician on duty. Reevaluation was conducted by two experienced emergency physicians (MMH, WS), blinded to all clinical data. The ST scores measured by all three physicians were averaged and used for analysis. In the case of a marked difference between the physician (ie, >2 mm difference), the ECG was reanalyzed by all three emergency physicians together in an attempt to reach a consensus. The interobserver variability was 96%.
Patients with evidence of acute congestive heart failure on admission or severe rhythm disturbances at the time of the initial ECG were excluded from analysis.
Acute congestive heart failure was defined as evidence of bibasilar rales over the lungs that did not clear with coughing, a third-sound gallop over the heart and signs of congestion in one of the subsequent chest radiographs routinely performed 12 and 24 hours after ED admission. Radiographic signs of acute congestive heart failure were central or perihilar infiltrates, increased size of vessels serving the upper portions of the lungs in the upright position, and increased prominence of interlobular septa (usually bilateral and symmetric).
Severe rhythm disturbances included bradyarrhythmias (asystole, type 2 second-degree or third-degree atrioventricular block, bradycardia associated with hypotension [systolic blood pressure <90 mm Hg] requiring atropine or insertion of a temporary pacemaker), and tachyarrhythmias (ventricular fibrillation, ventricular tachycardia requiring electrical or chemical cardioversion, rapid atrial fibrillation associated with hypotension [systolic blood pressure <90 mm Hg] requiring digitalis or amiodarone).
All patients who died during the 24 hours after admission to the ED were noted.
We retrieved the following data from the ED charts: age, sex, duration of chest pain, peak creatine kinase (CK) and CK-MB, and complications noted during the 24 hours after ED admission. ST score was calculated according to the previously noted criteria. On the basis of these data, we established a model to predict the appearance of early complications according to the extent of the ST score in the admission ECG.
The following parameters were classified as independent variables in the model: age, sex, interval between onset of pain and the start of thrombolytic therapy, and the calculated sum of ST-segment elevation in the admission ECG.
Evidence of acute congestive heart failure or severe rhythm disturbances in the 24 hours after ED admission were the dependent or outcome variables in this model. Cutoff points were identified for the greatest sensitivity or specificity for the prediction of early complications. The influence of time from onset of pain to treatment, age, and sex was evaluated with the use of a multivariate regression analysis.
Diagnostic performance was described in terms of areas under the receiver-operator curves (ROCs) in accordance with the methods described previously. [16] [17] [18] The ROC analysis software of Centor and Keightley (Blue Ridge Express) was used to obtain area calculations.
We described continuous data with the mean and SD or median and interquartile range (IQR) as appropriate. We used the unpaired Student t test or the nonparametric Mann-Whitney U test for the comparison of groups and the chi2 test for comparisons of proportions. Logistic-regression analysis was used for the estimation of odds ratios (ORs). Numeric values were rounded to the nearest integer. Two-tailed P values less than .05 were considered statistically significant.
TABLE 1 -- General data. Features Anterior MI Inferior MI P
No. of patients 119 124
Age (yr) [mean±SD] 57.1±12.2 56.2±11.5 NS
Sex (M/F) 98/21 96/28 NS
Median peak CK
value (U/L) [IQR] 1,221 (502-1,980) 724 (399-1,115) .006
Median peak CK-MB
value (U/L) [IQR] 120 (72-194) 85 (45-130) .004
ST score (mm)
[mean±SD] 14.4±9.9 8.3±4.6 <.001
Median time to therapy
(min) [IQR] 110 (75-175) 110 (85-218) NS
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RESULTS
We included 243 patients (194 men, 49 women) with a mean±SD age of 56.6±11.8 years in the study (Table 1) . On the basis of electrocardiographic data, MI was located in the anterior wall in 119 patients and in the inferior wall in 124. Peak CK and CK-MB values were significantly greater in patients with anterior-wall infarction compared with those who had sustained inferior-wall infarctions (CK: 1,221 versus 724 U/L, P=.006; CK-MB: 120 versus 85 U/L, P=.004). Overall, in 103 patients (anterior MI: n=53; inferior MI: n=50; NS) either acute congestive heart failure (anterior MI: n=30; inferior MI: n=16; P=.03) or a rhythm disturbance (anterior MI: n=23; inferior MI: n=34; NS) was observed. The median interval from onset of pain to start of thrombolytic therapy was equal in patients with anterior and inferior MI (anterior MI: 110 minutes, IQR=75 to 175; inferior MI: 110 minutes, IQR=85 to 218; NS). Three patients died in the 24 hours after ED admission (anterior MI: n=2; inferior MI: n=1). Causes of death were cardiogenic shock (n=2) and left ventricular rupture (n=1).
In patients with evidence of complications, the sum of ST-segment elevation was significantly higher compared with
Figure 1. ROC curve showing the performance of ST score with regard to the prediction of early complications in patients with anterior MI.
that of patients without complications. This difference was observed in patients with anterior and inferior myocardial infarction (anterior MI: 10.3 versus 19.4 mm, P<.001; inferior MI: 6.9 versus 10.4 mm; P<.001). No significant differences were observed between patients with congestive heart failure and those with rhythm disturbances (anterior MI: 18.7 versus 15.9 mm, P=.42; inferior MI: 10.1 versus 9.5 mm; NS). The mean±SD ST score for the patients who died during the first 24 hours was 21.3±4.6 mm.
The number of leads with ST-segment elevation was significantly higher in patients with anterior MI and early complications than in those without serious events (4.2±1.2 versus 5.7±1.8, P<.05). In patients with inferior MI no significant difference was observed (3.3±.9 versus 3.4±.9, NS). The ST score divided by the number of leads with ST-segment elevation revealed a significantly higher score in patients with early complications compared with those without complications (anterior MI: 2.3±1.3 versus 3.6±1.9 mm/lead, P<.001; inferior MI: 1.9±.9 versus 3.0±1.4 mm/lead, P<.001). ROC curves show the performance of admission ST score in predicting early complications in anterior MI (Figure 1) . The mean±SD area under the curve is .80±.04. The optimal cutoff point maximizing sensitivity and specificity was found
Figure 2. ROC curve showing the performance of ST score with regard to the prediction of early complications in patients with inferior MI.
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at 13 mm, for a sensitivity of 79% and a specificity of 73%. The relative risk (RR) was significantly greater in patients above the cutoff value than in those below the cutoff (RR, 2.98; 95% confidence interval [CI], 1.9 to 4.8).
ROC curves show the performance of ST score on admission by early complications in inferior MI (Figure 2) . The mean±SD area under the curve was .72±.05. The optimal cutoff point was found at 9 mm, for a sensitivity of 64% and specificity of 68%. The RR is significantly greater in patients above the cutoff value compared with those below the cutoff value (RR, 2.1; IQR, 1.4 to 3.2).
With the cutoff values derived from ROC analysis, logistic-regression analysis showed that the admission ST score on admission was an independent predictor of the occurrence of early complications in patients with anterior MI (OR, 9.7; 95% CI, 3.9 to 25.1; P<.0001) and in patients with inferior MI (OR, 5.0; 95% CI, 2.0 to 12.8; P=.0002) (Table 2 , Figure 3) . An increase of 1.0 mm in ST score increases the odds of complications by 1.1 (95% CI, 1.1 to 1.2) for anterior MI and by 1.2 (95% CI, 1.1 to 1.4) for inferior MI. No other clinical variables available at the time of ED presentation were significantly associated with the occurrence of early complications in patients with anterior or inferior MI.
DISCUSSION
The initial ECG is frequently used to predict acute MI, serious complications and in-hospital mortality. [1] [2] [3] These studies were designed mainly to identify patients at high risk for a subsequent MI. [1] [2] [3] [4] [5] [6] Therefore patients with suspected acute MI were classified into high- and low-risk groups on the
TABLE 2 -- Multivariate analysis for the occurrence of early complications.
Anterior MI (n=119) Inferior MI (n=124)
Features OR (95% CI) P OR (95% CI) P
Age (yr)
70 1.0 NS 1.0 NS
>70 1.36 (.24-7.45)
.53 (.14-1.8)
Sex .84 (.22-3.29) NS .52 (.18-1.45) NS
Time to therapy
(min)
120 1.0 NS 1.0 NS
>120 1.46 (.55-3.99)
1.45 (.6-3.55)
ST score (mm)
13 1.0 <.0001
>13 9.73 (3.94-25.1)
9
1.0 .0002
>9
4.98 (2.04-12.84)
basis of evidence or absence of specific electrocardiographic patterns (eg, ST-segment elevation, left bundle-branch block, left ventricular hypertrophy, ST-segment depression). [1] Brush et al [1] demonstrated that patients with such "positive" admission-ECG findings had a significantly greater risk of a subsequent acute MI, serious complications or death than those with "negative" ECG findings. Also, patients with minimally abnormal admission ECG findings had a low risk of subsequent MI. [7]
In contrast, our study included patients with evidence of acute MI and was initiated to separate MI patients into those at high and low risk for subsequent complications in the 24 hours after admission on the basis of the ST score. In our series of 243 patients, the ST score was a good predictor of early complications during the 24 hours after acute MI; the ST score was significantly higher in patients with evidence of early complications compared with those without any events. This difference was observed in patients with anterior and inferior Mis, indicating that the ST score can be used independent of the infarct location. We also identified cutoff values of the ST score to calculate the risk for the occurrence of early complications. If the sum of the ST-segment elevations was greater than these cutoff values, the odds of early complications were 10 times greater in patients with anterior MI and five times greater in patients with inferior MI (Figure 3) . Other factors--age, sex, and time between onset of pain and thrombolysis--had no effect on the occurrence of early complications. Therefore ST
Figure 3. Schematic representation of the frequency of early complications in patients with anterior or inferior myocardial infarction according to the magnitude of the ST score on the admission ECG.
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score remains the only predictor of the occurrence of early complications in patients with acute MI.
The extent of the ST score is determined by the total number of leads and by the extent of ST-segment elevation in each lead with ST-segment changes. A higher ST score, therefore, can be due to an increase in the total number of leads with ST-segment elevation, an increase in the extent of ST-segment elevation in each lead, or both.
In patients with anterior MI and early complications increased ST score is caused not only by greater ST-segment elevation in each lead but by a higher total number of leads with ST-segment elevations. Therefore ST score may reflect the area of endangered myocardium in patients with anterior MI. Our data are in line with the findings of previously published reports demonstrating a relationship between ST score and infarct size. [19] [20] These reports also showed a correlation between the amount of ST-segment elevation and serious complications or death. [4] [21] [22] Figueras [4] et al reported a significant relationship between high ST-segment elevation and left ventricular rupture in patients with acute inferior MI. [4] Nielsen et al [21] demonstrated that "major ST elevations" were associated with a higher risk of fatal events compared with the patients with "minor ST elevations." These data are confirmed by our findings; the three patients who died in the first 24 hours were characterized by above-average ST scores (mean, 21.3 mm).
In contrast, the higher ST score in patients with inferior MI and early complications is caused by a greater ST-segment elevation in each affected lead; the total number of leads involved was similar in patients with and without early complications. Therefore, in patients with inferior MI, ST score only partially reflects the area of endangered myocardium.
Because ST-segment depressions are frequently observed in patients with inferior MI, [23] the exclusion of ST-segment depressions from ST-score calculation seems to be responsible for the lack of correlation between the area of endangered myocardium and ST score in patients with inferior MI. The calculation of the ST score without ST-segment depressions also contributes to the significant difference in the cutoff values between patients with anterior and inferior MI (9 mm versus 13 mm). However, ST-segment depression may be due to many nonischemic and chronic conditions (eg, left ventricular hypertrophy, treatment with digoxin or digitoxin, bundle-branch block) that may interfere with the acute ST-segment depressions caused by myocardial ischemia. Therefore inclusion of ST-segment depressions in such patients may lead to an increased ST score, resulting in decreased specificity. Currently the ST-scoring system is not suitable for patients with posterior infarction; these patients mainly exhibit ST-segment depressions. Further studies are required to evaluate the effect of the inclusion of ST-segment depressions in the ST score on sensitivity and specificity of our cutoff values in patients with inferior MI.
It must be emphasized that the results of our study are restricted to patients undergoing thrombolysis. The interval between onset of pain and treatment ranged from a minimum of 30 minutes to a maximum of 6 hours. It must also be emphasized that this interval may be too small to have any influence on the relationship between ST score and early complications. Whether longer intervals (eg, 6 to 12 hours between the onset of pain and the start of treatment) have any influence on the occurrence of early complications cannot be answered with our data. Also, the association between the area of endangered myocardium and the extent of ST score may be weak, especially in patients with inferior MI. Other methods such as echocardiography, scintigraphy or even biochemical markers may provide more accurate data about the area of endangered myocardium or infarct size. [24] [25] [26] [27] [28] Therefore these methods may be used to predict early complications more precisely than may the ST score. However, these methods require technical or laboratory skills, which may not be available in all EDs on a 24-hour basis. Additionally, none of these parameters is as easily available at the time of admission as the ST score.
Despite these limitations, our data have important clinical implications in the treatment of patients with acute MI. First, evaluation of the ST score on the initial ECG provides a simple method with which to identify patients at high risk for early complications. It follows that the patient at risk for complications may be transferred to an intermediate care unit with telemetric monitoring and trained nursing personnel. This procedure may save costs without compromising patient care. Second, patients at high risk of complications may be considered for a more aggressive therapeutic approach (eg, angioplasty or coronary artery bypass grafting) to reduce the risk of severe early complications.
In conclusion, the absolute ST score is useful in estimating the probability of early complications in patients with acute MI receiving thrombolytic therapy. A cutoff value of 13 mm for anterior MI and 9 mm for inferior MI risk-stratifies patients into high- and low-risk subgroups for development of acute congestive heart failure and severe rhythm disturbances during the first 24 hours of hospitalization. We therefore assume that the calculation of ST-segment elevation score on the admission ECG is clinically relevant because patients with acute MI may be classified as being at high or low risk shortly after ED admission. This stratification may have an important effect on the further treatment of the patient.
569
REFERENCES
1. Brush JE, Brand DA, Acampora D, et al.: Use of the initial electrocardiogram to predict inhospital complications of acute myocardial infarction. N Engl J Med 1985;312:1137-1141.
2. Fesmire FM, Percy RF, Wean RL, et al: Risk stratification according to the initial electrocardiogram in patients with suspected acute myocardial infarction. Arch Intern Med 1989;149:1294-1297.
3. Young MJ, McMahon LF, Stross JK: Prediction rules for patients with suspected myocardial infarction: Applying guidelines in community hospitals. Arch Intern Med 1989;147:1219-1222.
4. Figueras J, Curos A, Cortadellas J, et al: Relevance of electrocardiographic findings, heart failure, and infarct site in assessing risk and timing of left ventricular free wall rupture during acute myocardial infarction. Am J Cardiol 1995;76:543-547.
5. Zalenski RJ, Sloan EP, Chen EH, et al: The ED ECG and immediately life-threatening complications in initially uncomplicated suspected myocardial ischemia. Ann Emerg Med 1988;17:221-226.
6. Stark ME, Vacek JL: The initial electrocardiogram during admission for myocardial infarction: Use as a predictor of clinical course and facility utilization. Arch Intern Med 1987;147:843-846.
7. Slater DK, Hlatky MA, Mark DB, et al: Outcome in suspected acute myocardial infarction with normal or minimally abnormal admission electrocardiographic findings. Am J Cardiol 1987;60: 766-770.
8. Zehender M, Kasper W, Kauder E, et al: Right ventricular infarction as an independent predictor of prognosis after inferior myocardial infarction. N Engl J Med 1993;328:981-988.
9. Zehender M, Kasper W, Kauder E, et al: Eligibility for and benefit of thrombolytic therapy in inferior myocardial infarction: Focus on the prognostic importance of right ventricular infarction. J Am Coll Cardiol 1994;24:362-369.
10. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group: ISIS-4: A randomized factorial trial assessing early captopril, oral mononitrate, and intravenous magnesium sulphate in 58.050 patients with suspected acute myocardial infarction. Lancet 1995;345:669- 685.
11. Neuhaus KL, von Essen R, Tebbe U, et al: Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: Results of the rt-Pa-APSAC patency study (TAPS). J Am Coll Cardiol 1992;19:892-893.
12. Birnbaum Y, Scamvsky S, Blum A, et al: Prognostic significance of the initial electrocardiographic pattern in a first acute anterior wall myocardial infarction. Chest 1993;103:1681-1687.
13. Wellens HJJ, Conover MB: The ECG in Emergency Decision Making, ed 1. Philadelphia: WB Saunders, 1992:1-26.
14. Clemmensen P, Grande P, Saunamaki K, et al: Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts. J Am Coll Cardiol 1990;5:1252-1257.
15. Aldrich HR, Wagner NB, Boswick J, et al: Use of initial ST segment deviation for prediction of final electrocardiographic size of acute myocardial infarcts. Am J Cardiol 1988;61:749-753.
16. Swets JA: Measuring the accuracy of diagnostic systems. Science 1988;240:1285-1293.
17. Centor RM: Signal detectability: The use of ROC curves and their analyses. Med Decis Making 1991;11:102-106.
18. Metz CE: ROC methodology in radiologic imaging. Invest Radiol 1986;21:720-733.
19. Mamko PR, Libby P, Covell JW, et al: Precordial ST segment elevation mapping: An atraumatic method for assessing alterations in the extent of myocardial injury: The effect of pharmacologic and hemodynamic interventions. Am J Cardiol 1972;29:223-230.
20. Muller JE, Maroko PR, Braunwald E: Evaluation of precordial mapping as a means of assessing changes in myocardial ischemic injury. Circulation 1975:52:16-27.
21. Nielsen BL: ST segment elevation in acute myocardial infarction: Prognostic importance. Circulation 1973;48:338-345.
22. Mauri F, Gasparini M, Barbonaglia L, et al: Prognostic significance of the extent of myocardial injury in acute myocardial infarction treated by streptokinase (the GISSI trial). Am J Cardiol 1989; 63:1291-1295.
23. Bates ER, Clemmensen PM, Califf RM, et al: Precordial ST-segment depression predicts a worse prognosis in inferior infarction despite reperfusion therapy. J Am Coll Cardiol 1990;16: 1538-1544.
24. Bonow RO, Dilsizian V, Cuocolo A, et al: Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction: Comparison of thallium scintigraphy with reinjection and PET imaging with 18 F-fluorodeoxyglucose. Circulation 1991;83:26-37.
25. Schiller N, Shah P, Crawford M, et al: American Society of Echocardiography Committee on Standards, Subcommittee on Quantification of Two-Dimensional Echocardiograms. J Am Soc Echo 1989;2:358-367.
26. Iliceto S, Marangelli V, Marchese A, et al: Myocardial contrast echocardiography in acute myocardial infarction: Pathophysiological background and clinical applications. Eur Heart J 1996;17:344-353.
27. Hamm CW, Katus HA: New biochemical markers for myocardial cell injury. Curr Opin Cardiol 1995;10:355-360.
28. Hirschl MM, Gwechenberger M, Binder T, et al: Assessment of myocardial injury by serum tumour necrosis factor alpha measurements in acute myocardial infarction. Eur Heart J 1996;17:1852-1859.
APPENDIX
TABLE 3 -- Sensitivity and specificity of different cutoff values in patients with anterior MI Cutoff Value
(ST Score [mm]) Sensitivity Specificity
51 .00 .98
50 .02 .98
42 .04 .97
38 .06 .97
31 .08 .97
30 .13 .97
29 .17 .97
28 .19 .97
27 .23 .97
26 .25 .97
25 .26 .95
24 .32 .95
23 .38 .95
22 .40 .95
21 .45 .95
20 .45 .92
19 .51 .91
18 .53 .89
17 .55 .86
16 .55 .83
15 .60 .82
14 .72 .79
13 .79 .73
12 .79 .68
11 .85 .65
10 .87 .56
9 .87 .50
8 .89 .35
7 .94 .32
6 .96 .27
5 1.00 .23
4 1.00 .15
3 1.00 .08
2 1.00 .02
0 1.00 .00
TABLE 4 -- Sensitivity and specificity of different cutoff values in patients with inferior MI Cutoff Value
(ST Score [mm]) Sensitivity Specificity
30 .02 1.00
21 .02 .99
18 .06 .97
17 .06 .96
16 .08 .96
15 .16 .95
14 .24 .93
13 .30 .93
12 .40 .93
11 .54 .86
10 .56 .80
9 .64 .68
8 .70 .58
7 .78 .53
6 .86 .41
5 .90 .32
4 .96 .22
3 .96 .07
2 .98 .00
1 1.00 .00
Em
Thursday, May 7, 2009
What is an acute myocardial infarction?
Russell V. Luepker
School of Public Health, University of Minnesota, Minneapolis, MN, USA
The accurate diagnosis of acute myocardial infarction (AMI) is crucial for many reasons. For the practicing physician, the diagnosis has clear and directive therapeutic implications. For the hospital administrator, it has important influences on resource allocation and quality assurance. For the clinical trialist, it defines outcomes in studies of new therapies. For the epidemiologist, case definitions are essential for understanding incidence and prevalence and for monitoring disease trends in the population. However, despite its importance, the definition of AMI is in flux, leading to ambiguity and confusion for clinicians, administrators, trialists and epidemiologists.
Common case-criteria for AMI developed in the 1960s from a need to establish heart disease registries. Most of these efforts focused on discharge diagnoses and retrospective surveillance. The criteria became the widely used 'World Health Organization (WHO) criteria' [1,2], and included a triad of elements: classical symptoms, enzyme elevation and electrocardiographic (ECG) changes, particularly the newly developed Q-waves. But these were ambiguous ‘criteria’, enabling clinicians and investigators to use them as they saw fit, and yet still claim to be using the WHO standard. This ambiguity meant that comparisons of AMI between centers and over time were difficult and often invalid.
The field advanced in the 1980s with the advent of large surveillance projects that developed explicit definitions for symptoms, enzyme levels and ECG patterns. The WHO MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease) study and parallel efforts in the United States exemplified this advance [3,4].
Unfortunately, the discharge diagnoses approach and retrospective chart abstraction used in these trials did not allow for an immediate diagnosis, which is needed for acute therapy, where clinicians must make decisions with limited information. Furthermore, the changing presentation of AMI was not taken into account, and the various new biomarkers were not used.
Changing treatments
The emergence of acute reperfusion therapies implied a need for rapid diagnosis. Thrombolysis and percutaneous angioplasty, early treatment interventions designed to restore blood flow, were highly effective but only when performed within hours of the onset of symptoms.
New biomarkers
The advent of new biomarkers, specifically troponins, also dramatically altered the field. Troponins are highly sensitive and specific blood markers of cardiac myocyte damage [5-7]. In comparison with older enzyme markers such as lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT), creatine kinase (CK) and CK isoenzyme MB, they represent a ‘sea change’ in diagnosis, because they allow smaller infarcts to be detected - and to be detected more quickly.
Changing presentation
Finally, the presentation of the disease began to change as traditional Q-wave infarctions diminished and a more subtle form of ECG-based AMI became prevalent [8].
This combination of clinical needs, improved diagnostic technology and changes in the presentation led to widespread interest in revising the diagnostic criteria for AMI, resulting in a series of new and widely endorsed AMI definitions.
In 2000, a joint working group of the European Society of Cardiology and American College of Cardiology developed a statement on the redefinition of myocardial infarction [9]. It addressed both the need for a more rapid diagnosis and the advent of new biomarker technologies. It also suggested that diagnostic imaging would play a role in case definitions.
Later on, in 2003, an American Heart Association (AHA), WHO and US National Institutes of Health (NIH) group put forward definitions necessary for population surveillance of cardiovascular disease [10]. These epidemiological criteria focused on longer-term surveillance issues, in which consistency of case definition is crucial. The group also considered comparisons between modern and earlier enzyme-defined cases.
Most recently, in 2007, a combined group of all these organizations discussed a universal definition of myocardial infarction. It refined and better described a number of clinical situations in which myocardial infarction might be considered, including inadequate oxygen supply, trauma, and myocardial infarction associated with cardiac procedures [11].
The results of the technological advances and the new definitions are dramatic. A number of studies have demonstrated that the use of troponins can lead to substantial increases in the number of patients hospitalized with AMI. In one study, using troponin as a biomarker instead of CK or CK-MB resulted, respectively, in a 0-320% or 3.9-195% increase in AMI hospitalizations [12].
These differences are debated in the literature, but most investigators suggest that using troponin as a biomarker results in the detection of milder myocardial infarctions [13-15]. These ’small‘ AMIs nonetheless carry prognostic significance, because long-term follow-up demonstrates that even minor perturbations are associated with increased long-term mortality [16].
This trend will be enhanced by the advent of ultrasensitive cardiac troponin markers, which enable clinicians to reliably detect even lower levels of troponin [17]. One result of more sensitive markers is the revelation that a mild elevation in troponins is associated with other cardiac and non-cardiac diseases. These include a variety of pathologies, from heart failure to pulmonary embolisms and renal failure. In addition, extreme exertion is associated with a mild elevation in troponins [11]. These observations add confusion to the field.
Given these recent changes, what are reasonable recommendations? It is apparent that the contemporary diagnosis of AMI is driven by biomarkers, specifically troponins. Using these markers in combination with symptoms will result in the diagnosis of AMI even in the setting of negative cardiograms. For the emergency reperfusion situation, a single biomarker and/or cardiographic changes might be all that is available and adequate to make a diagnosis for reperfusion treatment. For monitoring disease trends and for trials, multiple markers - at least 2 - in an ascending or descending pattern in association with symptoms are essential for making the diagnosis.
Conclusions
In the future, we will see a continuing evolution of the definition of AMI as more sensitive measures of myocardial damage emerge. Disease rates will rise in the setting of milder cases, as a result of more-sensitive measures. These changes should provide direction for clinicians to implement the most effective therapies for their patients, based on an improved understanding of the underlying pathophysiology. For those interested in disease outcomes, a continuing evolution of data-based criteria is needed.
References
1. Weinstein BJ, Epstein FH. Comparability of criteria and methods in the epidemiology of cardiovascular disease. Report of a survey. Circulation 1964;30:643-653.
2. World Health Organization. Working group on the establishment of ischaemic heart disease registers: Report of the fifth working group. 1971; WHO Report No. Eur 8201(5); Copenhagen.
3. Gillum RF, Folsom A, Luepker RV, et al. Sudden death and acute myocardial infarction in a metropolitan area, 1970-1980. The Minnesota Heart Survey. N Engl J Med 1983;309:1353-1358.
4. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, et al. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 1994;90:583-612.
5. Apple FS. Cardiac troponin monitoring for detection of myocardial infarction: Newer generation assays are here to stay. Clinica Chimica Acta 2007;380:1-3.
6. Apple FS, Jesse RL, Newby LK, et al. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Clin Chem 2007;53:547-551.
7. Saenger AK, Jaffe AS. Requiem for a heavyweight: the demise of creatine kinase-MB. Circulation 2008;118:2200-2206.
8. Crow RS, Hannan PJ, Jacobs DR Jr, et al. Eliminating diagnostic drift in the validation of acute in-hospital myocardial infarction - implication for documenting trends across 25 years: the Minnesota Heart Survey. Am J Epidemiol 2005;161:377-388.
9. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined - a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-969.
10. Luepker RV, Apple FS, Christenson RH, et al. Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation 2003;108:2543-2549.
11. Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007;28:2525-2538.
12. White HD. Evolution of the definition of myocardial infarction: What are the implications of a new universal definition? Heart 2008;94:679-684.
13. Polanczyk CA, Schneid S, Imhof BV, et al. Impact of redefining acute myocardial infarction on incidence, management and reimbursement rate of acute coronary syndromes. Int J Cardiol 2006;107:180-187.
14. Salomaa V, Ketonen M, Koukkunen H, et al. The effect of correcting for troponins on trends in coronary heart disease events in Finland during 1993-2002: the FINAMI study. Eur Heart J 2006;27:2394-2399.
15. Salomaa V, Koukkunen H, Ketonen M, et al. A new definition for myocardial infarction: what difference does it make? Eur Heart J 2005;26:1719-1725.
16. Hochholzer W, Buettner HJ, Trenk D, et al. New definition of myocardial infarction: impact on long-term mortality. Am J Med 2008;121:399-405.
17. Casals G, Filella X, Auge JM, Bedini JL. Impact of ultrasensitive cardiac troponin I dynamic changes in the new universal definition of myocardial infarction. Am J Clin Pathol 2008;130:964-968.
School of Public Health, University of Minnesota, Minneapolis, MN, USA
The accurate diagnosis of acute myocardial infarction (AMI) is crucial for many reasons. For the practicing physician, the diagnosis has clear and directive therapeutic implications. For the hospital administrator, it has important influences on resource allocation and quality assurance. For the clinical trialist, it defines outcomes in studies of new therapies. For the epidemiologist, case definitions are essential for understanding incidence and prevalence and for monitoring disease trends in the population. However, despite its importance, the definition of AMI is in flux, leading to ambiguity and confusion for clinicians, administrators, trialists and epidemiologists.
Common case-criteria for AMI developed in the 1960s from a need to establish heart disease registries. Most of these efforts focused on discharge diagnoses and retrospective surveillance. The criteria became the widely used 'World Health Organization (WHO) criteria' [1,2], and included a triad of elements: classical symptoms, enzyme elevation and electrocardiographic (ECG) changes, particularly the newly developed Q-waves. But these were ambiguous ‘criteria’, enabling clinicians and investigators to use them as they saw fit, and yet still claim to be using the WHO standard. This ambiguity meant that comparisons of AMI between centers and over time were difficult and often invalid.
The field advanced in the 1980s with the advent of large surveillance projects that developed explicit definitions for symptoms, enzyme levels and ECG patterns. The WHO MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease) study and parallel efforts in the United States exemplified this advance [3,4].
Unfortunately, the discharge diagnoses approach and retrospective chart abstraction used in these trials did not allow for an immediate diagnosis, which is needed for acute therapy, where clinicians must make decisions with limited information. Furthermore, the changing presentation of AMI was not taken into account, and the various new biomarkers were not used.
Changing treatments
The emergence of acute reperfusion therapies implied a need for rapid diagnosis. Thrombolysis and percutaneous angioplasty, early treatment interventions designed to restore blood flow, were highly effective but only when performed within hours of the onset of symptoms.
New biomarkers
The advent of new biomarkers, specifically troponins, also dramatically altered the field. Troponins are highly sensitive and specific blood markers of cardiac myocyte damage [5-7]. In comparison with older enzyme markers such as lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT), creatine kinase (CK) and CK isoenzyme MB, they represent a ‘sea change’ in diagnosis, because they allow smaller infarcts to be detected - and to be detected more quickly.
Changing presentation
Finally, the presentation of the disease began to change as traditional Q-wave infarctions diminished and a more subtle form of ECG-based AMI became prevalent [8].
This combination of clinical needs, improved diagnostic technology and changes in the presentation led to widespread interest in revising the diagnostic criteria for AMI, resulting in a series of new and widely endorsed AMI definitions.
In 2000, a joint working group of the European Society of Cardiology and American College of Cardiology developed a statement on the redefinition of myocardial infarction [9]. It addressed both the need for a more rapid diagnosis and the advent of new biomarker technologies. It also suggested that diagnostic imaging would play a role in case definitions.
Later on, in 2003, an American Heart Association (AHA), WHO and US National Institutes of Health (NIH) group put forward definitions necessary for population surveillance of cardiovascular disease [10]. These epidemiological criteria focused on longer-term surveillance issues, in which consistency of case definition is crucial. The group also considered comparisons between modern and earlier enzyme-defined cases.
Most recently, in 2007, a combined group of all these organizations discussed a universal definition of myocardial infarction. It refined and better described a number of clinical situations in which myocardial infarction might be considered, including inadequate oxygen supply, trauma, and myocardial infarction associated with cardiac procedures [11].
The results of the technological advances and the new definitions are dramatic. A number of studies have demonstrated that the use of troponins can lead to substantial increases in the number of patients hospitalized with AMI. In one study, using troponin as a biomarker instead of CK or CK-MB resulted, respectively, in a 0-320% or 3.9-195% increase in AMI hospitalizations [12].
These differences are debated in the literature, but most investigators suggest that using troponin as a biomarker results in the detection of milder myocardial infarctions [13-15]. These ’small‘ AMIs nonetheless carry prognostic significance, because long-term follow-up demonstrates that even minor perturbations are associated with increased long-term mortality [16].
This trend will be enhanced by the advent of ultrasensitive cardiac troponin markers, which enable clinicians to reliably detect even lower levels of troponin [17]. One result of more sensitive markers is the revelation that a mild elevation in troponins is associated with other cardiac and non-cardiac diseases. These include a variety of pathologies, from heart failure to pulmonary embolisms and renal failure. In addition, extreme exertion is associated with a mild elevation in troponins [11]. These observations add confusion to the field.
Given these recent changes, what are reasonable recommendations? It is apparent that the contemporary diagnosis of AMI is driven by biomarkers, specifically troponins. Using these markers in combination with symptoms will result in the diagnosis of AMI even in the setting of negative cardiograms. For the emergency reperfusion situation, a single biomarker and/or cardiographic changes might be all that is available and adequate to make a diagnosis for reperfusion treatment. For monitoring disease trends and for trials, multiple markers - at least 2 - in an ascending or descending pattern in association with symptoms are essential for making the diagnosis.
Conclusions
In the future, we will see a continuing evolution of the definition of AMI as more sensitive measures of myocardial damage emerge. Disease rates will rise in the setting of milder cases, as a result of more-sensitive measures. These changes should provide direction for clinicians to implement the most effective therapies for their patients, based on an improved understanding of the underlying pathophysiology. For those interested in disease outcomes, a continuing evolution of data-based criteria is needed.
References
1. Weinstein BJ, Epstein FH. Comparability of criteria and methods in the epidemiology of cardiovascular disease. Report of a survey. Circulation 1964;30:643-653.
2. World Health Organization. Working group on the establishment of ischaemic heart disease registers: Report of the fifth working group. 1971; WHO Report No. Eur 8201(5); Copenhagen.
3. Gillum RF, Folsom A, Luepker RV, et al. Sudden death and acute myocardial infarction in a metropolitan area, 1970-1980. The Minnesota Heart Survey. N Engl J Med 1983;309:1353-1358.
4. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, et al. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 1994;90:583-612.
5. Apple FS. Cardiac troponin monitoring for detection of myocardial infarction: Newer generation assays are here to stay. Clinica Chimica Acta 2007;380:1-3.
6. Apple FS, Jesse RL, Newby LK, et al. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Clin Chem 2007;53:547-551.
7. Saenger AK, Jaffe AS. Requiem for a heavyweight: the demise of creatine kinase-MB. Circulation 2008;118:2200-2206.
8. Crow RS, Hannan PJ, Jacobs DR Jr, et al. Eliminating diagnostic drift in the validation of acute in-hospital myocardial infarction - implication for documenting trends across 25 years: the Minnesota Heart Survey. Am J Epidemiol 2005;161:377-388.
9. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined - a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-969.
10. Luepker RV, Apple FS, Christenson RH, et al. Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation 2003;108:2543-2549.
11. Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007;28:2525-2538.
12. White HD. Evolution of the definition of myocardial infarction: What are the implications of a new universal definition? Heart 2008;94:679-684.
13. Polanczyk CA, Schneid S, Imhof BV, et al. Impact of redefining acute myocardial infarction on incidence, management and reimbursement rate of acute coronary syndromes. Int J Cardiol 2006;107:180-187.
14. Salomaa V, Ketonen M, Koukkunen H, et al. The effect of correcting for troponins on trends in coronary heart disease events in Finland during 1993-2002: the FINAMI study. Eur Heart J 2006;27:2394-2399.
15. Salomaa V, Koukkunen H, Ketonen M, et al. A new definition for myocardial infarction: what difference does it make? Eur Heart J 2005;26:1719-1725.
16. Hochholzer W, Buettner HJ, Trenk D, et al. New definition of myocardial infarction: impact on long-term mortality. Am J Med 2008;121:399-405.
17. Casals G, Filella X, Auge JM, Bedini JL. Impact of ultrasensitive cardiac troponin I dynamic changes in the new universal definition of myocardial infarction. Am J Clin Pathol 2008;130:964-968.
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