Improved early risk stratification and diagnosis of myocardial infarction, using a novel troponin I assay concept.

BACKGROUND: We evaluated the clinical performance of a novel cardiac troponin I (cTnI) assay specifically designed to improve the very early risk stratification in acute coronary syndromes. SUBJECTS AND METHODS: Serum and plasma samples (taken 0, 6-12 h and 24 h after admission) from 531 patients with suspected acute coronary syndrome were studied using a novel investigational cTnI assay, reference cTnI assay and myoglobin. The lowest cTnI concentration giving a total assay imprecision of 10% was used as the positive myocardial infarction (MI) cut-off value. RESULTS: At the time of admission, the investigational assay was positive in 27.9% of the patients, the reference cTnI assay was positive in only 17.5% (P < 0.001) and myoglobin in 24.1% (P = 0.067). Receiver operating characteristic (ROC) curve analysis for the detection of myocardial injury on admission gave area-under-curve (AUC) values of 0.937, 0.775 and 0.762, respectively (P < 0.001). Of those MI patients who presented within 3 h of symptom onset, 50.0% were identified by the investigational assay at the time of presentation, compared with 44.2% by myoglobin (P = 0.791) but only 11.5% by the reference assay (P < 0.001). CONCLUSIONS: The novel cTnI assay considerably improves the performance of cTnI as an early rule-in biomarker for MI.

Level of circulating phospholipase A2 in prediction of the prognosis of patients with suspected myocardial infarction.

OBJECTIVES: Atherosclerotic lesions result from inflammatory-proliferative responses of the endothelium and smooth muscle of the arterial wall. Poor prognosis of acute myocardial infarction (AMI) patients has been associated with elevated levels of acute phase proteins including C-reactive protein. We investigated the significance of circulating phospholipase A2 in the long-term prognosis of suspected AMI patients. METHODS: The concentration of phospholipase A2 was measured by an immunoassay in sera of 100 suspected AMI patients. Admission phospholipase A2 95 % fractile outliers were excluded to eliminate the effect of acute infectious diseases. The total and atherosclerotic mortalities were followed for a 4-year period. RESULTS: The most powerful prognostic limit for both admission (p = 0.02, RR = 2.6 and 95% CI = 1.2 to 5.6) and maximal (p = 0.06, RR = 2.4 and 95% CI = 0.96 to 5.9) phospholipase A2 groups was > or =8 microg/l. The admission phospholipase A2 level had an independent prognostic significance for atherosclerotic mortality (p = 0.04, RR = 2.4 and CI = 1.02 to 5.8) in multivariate analysis with CK-MB and age. CONCLUSIONS: The elevated serum phospholipase A2 level at admission is an independent predictor of long-term atherosclerotic mortality in patients with suspected AMI. The prognostic significance of phospholipase A2 weakens during hospitalisation concomitant to the onset of the acute inflammatory response to myocardial injury.

Cardiac decompensation during an ischemic event weakens the predictive power of myocardial injury markers.

Our objection was to find determinants of long-term outcome in routine data collected for differential diagnosis of suspected acute myocardial infarction. Study population consisted of 263 discharged patients who were initially hospitalized for differential diagnosis of suspected acute myocardial infarction between October 1992 and January 1993. Follow-up time for all cause and cardiac mortality was 5 years. The variables studied as predictors of outcome were computerized ECG, peak creatine kinase isoenzyme MB, peak troponin I, radiographic evidence of pulmonary congestion (cardiac decompensation), treatment for hyperlipidemia, hypertension or diabetes, smoking, previous myocardial infarction, age and gender. Total mortality was 32% at 5 years, of which 77% (64/83) was of cardiac origin. Pulmonary congestion in chest X-ray was the most powerful predictor of outcome (RR=3.3, 95% CI=2.0-5.2, P<0.001). In multivariate analysis congestion (RR=3.3, CI=2.0-5.2) was the only independent predictor of 5-year total mortality in addition to age (RR=1.06, CI=1.04-1.08). These two variables together with previous myocardial infarction (RR=1.9, CI=1.2-3.1) and hyperlipidemia (RR=2. 0, CI=1.1-3.5) were independent predictors of cardiac mortality. Radiographic evidence of cardiac decompensation during hospitalization is a strong and independent predictor of long-term outcome in unselected patients with suspected AMI. The predictive power of cardiac markers is confined to patients without pulmonary congestion.

Prediction of short-term outcome in patients with suspected myocardial infarction.

STUDY OBJECTIVE: Although specific cardiac injury markers have enhanced early patient classification, the ECG remains a necessary investigation in the acute phase of chest pain. Combined use of both tests could further improve the diagnostic and prognostic accuracy. METHODS: We studied 311 consecutive patients who came to the emergency department of a regional referral hospital for the differential diagnosis of acute chest discomfort. The admission ECG was classified using an automated interpretation program and tested together with elevated admission creatine kinase isoform MB (CK-MB) and cardiac troponin I (TnI) concentration for prediction of final myocardial injury (44%) and in-hospital mortality (14%). RESULTS: Combining the information from the admission ECG and cardiac markers, the sensitivity for becoming final myocardial injury (maximal CK-MB >/=11 microg/L) was 90% and specificity 61%. The proportion of false-negative results (10%) was independent of symptom duration. Age, positive ECG findings, and increased admission TnI levels were predictive for in-hospital mortality. CONCLUSION: The commonly available biochemical and ECG criteria allow risk stratification of patients with a suspected acute ischemic event. The data analysis can easily be automated and is independent of patient delay.

Is routine echocardiography useful in patients hospitalized for chest pain? Evidence of areal myocardial dysfunction detected only by echocardiography.

To assess the diagnostic value of routine two-dimensional echocardiography in the coronary care unit setting, we studied 81 unselected patients admitted for acute chest pain. Using electrocardiography (ECG), clinical history and serum markers of myocardial injury, the patients were retrospectively diagnosed as having had definite acute myocardial infarction (AMI) with (n=13) or without (n=31) previous infarction, possible AMI with (n=14) or without (n=15) previous infarction, and non-coronary cardiac or other causes of chest pain (n=8). Abnormal wall motion was observed in 75/77 patients with a cardiac origin of symptoms (sensitivity 97%), and there were no false-positive wall motion findings. In the 73 patients who were finally diagnosed with coronary artery disease (CAD), echocardiography showed wall motion abnormality in at least one additional coronary territory area in which there were no diagnostic ECG changes for 56% of patients with CAD (41/73) (P<0. 001). These areas were considered to be indicative of the presence of myocardium at risk for future cardiac events. We conclude that in addition to being a sensitive and accurate tool for detection of ischaemic wall motion abnormalities, two-dimensional echocardiography can give valuable information about the area of myocardium at risk. Therefore, therapeutic decisions can be affected by the findings of the routine echocardiographic examination, which is recommended even in unselected coronary care unit patients.

Epidemiological classification of acute myocardial infarction: time for a change?

AIMS: The classification of an acute ischaemic cardiac event is traditionally based on cardiac enzymes, electrocardiography (ECG) and clinical symptoms. The impact of new specific cardiac markers on the diagnostic classification of suspected acute myocardial infarction remains poorly studied. We therefore set out to compare the diagnostic and prognostic information provided by the MONICA code and a patient classification based on the maximal level of creatine kinase MB isoenzyme. The significance of typical pain and various ECG algorithms were separately analysed. METHODS AND RESULTS: The study population consisted of 311 consecutive patients who were evaluated for suspected acute myocardial infarction in a regional referral hospital. Patients were retrospectively classified according to the MONICA criteria, by a simplified code combining symptoms and creatine kinase MB, and solely using the maximal creatine kinase MB concentration. Total mortality was followed for 1 and 5 years. The creatine kinase MB based classification was shown to be the strongest predictor of mortality (OR=2.8-3.7, p<0.001) for outcome both at 1 and 5 years. Typical pain and a positive Minnesota ECG had no prognostic relevance. However, an analysis algorithm of the admission ECG was predictive of 1- and 5-year survival. CONCLUSIONS: The epidemiological classification of suspected acute myocardial infarction could be based solely on a specific cardiac marker, such as creatine kinase MB mass. This approach contains prognostic information and is accurate enough for the structured diagnosis of acute myocardial infarction. Other outcome predictors could be used to identify patient subgroups and assess therapy.

Computer-assisted electrocardiography in structured diagnosis of acute myocardial infarction.

The purpose of this study was to investigate the applicability of computerized electrocardiogram interpretation in classifying patients with suspected acute myocardial infarction. Computerized acquisition and analysis of the 12-lead electrocardiogram can increase the consistency and reduce the workload of patient classification. The serial electrocardiograms of 311 consecutive patients with suspected myocardial infarction were studied and a new computerized myocardial infarction (CMI) electrocardiographic classification was developed and compared with one commercially available and two manual codes. Statistically, there was almost no correlation between the four ECG codes. Compared with the WHO enzymatic criteria, the sensitivity of the CMI code toward detecting definite and possible infarction was 69.2% and 29.8% with a specificity of 62.1% and 79.7%, respectively. In subjects without previous infarction (n = 214) the sensitivity of the CMI code for definite enzymatic infarction was 71.9% and specificity 77.6%. Substituting the CMI for the Minnesota code had no effect on patient classification by the WHO MONICA criteria in 78% of patients with first infarction. Judged by cardiac macromolecular leakage, all electrocardiographic classifications of possible infarction were poorly correlated with myocardial tissue injury. We have developed a new computerized coding system to detect electrocardiographic myocardial infarction. The structure of the code allows interactive redefinition of criteria to meet user-defined needs. However, because of the weak relationship between electrocardiographic and biochemical criteria of myocardial injury, the role of ECG in the diagnostic classification of acute ischemic syndromes should be re-evaluated.

Automated electrocardiographic scores to estimate myocardial injury size during the course of acute myocardial infarction.

The automated ST-elevation score at admission and maximal QRS score during hospitalization provide good estimates of biochemical injury size during the course of first myocardial infarction. Being easily computerized, such scores could be used routinely to monitor the effect of injury-limiting therapy.