Drop-out from cardiovascular magnetic resonance in a randomized controlled trial of ST-elevation myocardial infarction does not cause selection bias on endpoints.

BACKGROUND: The extent of selection bias due to drop-out in clinical trials of ST-elevation myocardial infarction (STEMI) using cardiovascular magnetic resonance (CMR) as surrogate endpoints is unknown. We sought to interrogate the characteristics and prognosis of patients who dropped out before acute CMR assessment compared to CMR-participants in a previously published double-blinded, placebo-controlled all-comer trial with CMR outcome as the primary endpoint. METHODS: Baseline characteristics and composite endpoint of all-cause mortality, heart failure and re-infarction after 30 days and 5 years of follow-up were assessed and compared between CMR-drop-outs and CMR-participants using the trial screening log and the Eastern Danish Heart Registry. RESULTS: The drop-out rate from acute CMR was 28% (n = 92). These patients had a significantly worse clinical risk profile upon admission as evaluated by the TIMI-risk score (3.7 (± 2.1) vs 4.0 (± 2.6), p = 0.043) and by left ventricular ejection fraction (43 (± 9) vs. 47 (± 10), p = 0.029). CMR drop-outs had a higher incidence of known hypertension (39% vs. 35%, p = 0.043), known diabetes (14% vs. 7%, p = 0.025), known cardiac disease (11% vs. 3%, p = 0.013) and known renal function disease (5% vs. 0%, p = 0.007). However, the 30-day and 5-years composite endpoint rate was not significantly higher among the CMR drop-out ((HR 1.43 (95%-CI 0.5; 3.97) (p = 0.5)) and (HR 1.31 (95%-CI 0.84; 2.05) (p = 0.24)). CONCLUSION: CMR-drop-outs had a higher incidence of cardiovascular risk factors at baseline, a worse clinical risk profile upon admission. However, no significant difference was observed in the clinical endpoints between the groups.

Prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction and non-significant coronary artery disease.

BACKGROUND AND PURPOSE: We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD). METHODS: From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter <50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T >50ng/l or creatine kinase MB >4µg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion). RESULTS: Of the 871 patients admitted with suspected STEMI, 11% (n=95) had non-significant CAD. Of these, 67% (n=64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n=31) of patients, cardiac biomarkers were normal and ECG changes remained stationary. CONCLUSIONS: Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD.

Clinical significance of abnormal T waves in patients with non-ST-segment elevation acute coronary syndromes.

T-wave abnormalities are common electrocardiographic occurrences in patients with non-ST-segment elevation acute coronary syndromes. Although these abnormalities are considered relatively benign, physicians use them to guide therapies. The study objective was to examine the prognostic predictive information of T-wave abnormalities in the setting of unstable coronary artery disease. The T-wave abnormality criterion was based on a new set of normal T-wave amplitude limits differentiated by gender, age, electrocardiographic lead, and QRS axis. Four hundred sixty-eight patients suspected of an acute ischemic incident and considered ineligible for reperfusion therapy were included. Thirteen categories of T-wave abnormalities were tested prospectively. The primary 30-day end point was the combination of refractory angina, myocardial infarction, or death. Quantitative T-wave analysis in an electrocardiographic core laboratory revealed 6 of 13 prespecified categories of T-wave abnormalities that were significantly associated with an adverse outcome. T-wave abnormalities had no prognostic value when ST-segment depression was also present, but this occurred in only 7.9% of patients. T-wave abnormalities as the sole manifestation of ischemia were common (74.4%). Patients with abnormal T waves in > or =1 of 6 selected abnormality categories (70.3%) had a significantly higher risk of death, acute myocardial infarction, and refractory angina (11% vs 3%; p = 0.018). Thus, T-wave abnormalities in patients presenting with non-ST-segment elevation acute coronary syndromes are common and should not automatically be regarded as benign phenomena. Quantitative T- wave analysis provides optimal risk stratification.

[Eptifibatide (Integrilin)]. / Eptifibatide (Integrilin).

Eptifibatide (Integrilin) is a specific blocker of the glycoprotein IIb/IIIa receptor and an effective inhibitor of platelet aggregation. It reduces coronary events in patients with acute coronary syndromes and no elevation in the electrocardiographic ST segment. The present summary discusses the indications for the use of eptifibatide/Integrilin based on recent clinical trials and cost-benefit analyses.

The correlation between presenting ST-segment depression and the final size of acute myocardial infarcts in patients with acute coronary syndromes.

The use of reperfusion therapy in patients with ST elevation acute coronary syndromes had been established. However, reperfusion therapy is usually considered contra-indicated in those with ST depression, despite the knowledge that regional posterior infarction is typically indicated by ST depression maximal in leads V1 to V3 and nonregional subendocardial infarction is typically indicated by marked ST depression maximal in other leads. This study of patients with non-ST-elevation acute coronary syndromes investigates the quantitative relationship between presenting ST depression and final QRS changes in both of these subgroups. The final QRS score was significantly higher (2.44 points) than that of a control group with not ST depression, (1.55 points) in the group with maximal ST depression in V1 to V3 (P = 0.04). However, in the entire population, there was a highly significant correlation (P = .003) between the sum of the presenting ST depression and the final QRS score. Trials of reperfusion therapy will be required to determine if such evolution to electrocardiogram documented acute myocardial infarction can be prevented in patient with marked ST depression acute coronary syndromes.

Reduction of myocardial damage by prolonged treatment with subcutaneous low molecular weight heparin in unstable coronary artery disease. FRISC study group. Fragmin during Instability in Coronary Artery Disease.

AIMS: Several studies have proved heparin useful in treating patients with unstable coronary artery disease. The present study investigates whether Selvester QRS scoring for estimation of myocardial infarct size increases the incidence of detection of acute myocardial infarction during follow-up in a trial of patients with unstable angina/non-Q wave myocardial infarction treated with low molecular weight heparin or placebo. Finally it will be discussed how the QRS score, used for end-point identification, impacts on the power calculation in clinical trials. METHODS AND RESULTS: Electrocardiographic data on 1276 patients (644 in the placebo group, 632 in the low molecular weight heparin treatment group) were available. All ECGs were scored according to the Selvester QRS scoring method. At 40 days, more patients in the placebo than in the heparin group had achieved a threshold level of QRS score (25.9% vs 21.1%, P=0.05). Myocardial infarction, diagnosed as per the classic Q wave criteria, occurred in 3.7% of patients in the placebo group and in 0.9% in the low molecular weight heparin group at 6 days (P=0.002). At 40 days, the rates were 8.2% (placebo) and 5.7% (low molecular weight heparin, P=0.2). By combining the classic criteria with the Selvester method the myocardial infarction end-point rate in both groups was almost doubled (8.2% to 14.4% in the placebo group and 5.7% to 11.1% in the low molecular weight heparin group, P=0.07). The 216 patients with non-evaluable electrocardiograms did not differ from the 1276 patients as regards baseline characteristics; however, they had a significantly poorer prognosis, with a death/myocardial infarction rate of 20% at 40 days, compared with 8% among the patients with evaluable electrocardiograms (P<0.00001). CONCLUSION: Long-term subcutaneous treatment with low molecular weight heparin decreases the number of subsequent myocardial infarctions - determined both conventionally and by an increase in QRS score - in patients with unstable coronary artery disease. Silent myocardial infarctions detected by QRS score, as well as clinical myocardial infarctions, could be used as end-points in clinical trials of ischaemic heart disease and thus lower the population needed for obtaining statistical power.

Relative contributions of a single-admission 12-lead electrocardiogram and early 24-hour continuous electrocardiographic monitoring for early risk stratification in patients with unstable coronary artery disease.

Patients with unstable coronary syndromes are a heterogeneous group with varying degrees of ischemia and prognosis. The present study compares the prognostic value of a standard electrocardiogram (ECG) obtained at admission to the hospital with the information from 24-hour continuous electrocardiographic monitoring obtained immediately after admission. The admission ECGs and 24 hours of vectorcardiographic (VCG) monitoring from 308 patients admitted with unstable coronary artery disease were analyzed centrally regarding standard electrocardiographic ST-T changes, ST-vector magnitude (ST-VM), and ST change vector magnitude episodes. End points were death, acute myocardial infarction, and refractory angina pectoris within a 30-day follow-up period. ST-VM episodes (> or = 50 microV for > or = 1 minute) during VCG monitoring was the only independent predictor of death or acute myocardial infarction by multivariate analysis. ST-VM episodes during vectorcardiography was associated with a relative risk of 12.7 for having a cardiac event, hypertension was associated with a relative risk of 1.7, and ST depression on the admission ECG was associated with a relative risk of 5.7. Patients with ST depression at admission had an event rate (death or acute myocardial infarction) of 17% at 30-day follow-up. Patients without ST depression could further be risk stratified by 24 hours of VCG monitoring into a subgroup with ST-VM episodes at similar (8%) risk and a subgroup without ST-VM episodes at low (1%) risk (p = 0.00005). Continuous VCG monitoring provides important information for evaluating patients with unstable coronary artery disease. It is recommended that patients not initially estimated at high risk based on the admission ECG are referred for 24 hours of VCG monitoring for further risk stratification.

Effects of revascularization after first acute myocardial infarction on the evolution of QRS complex changes (the DANAMI trial). DANish Trial in Acute Myocardial Infarction.

The changes in QRS complex morphology associated with acute myocardial infarction (AMI) can resolve spontaneously over time. Whether complete revascularization of the infarct-related myocardial territory after AMI affects this QRS resolution has not been studied adequately. The present study compares the evolution of the changes in the QRS complex associated with AMI during 1-year follow-up in patients treated with or without revascularization after their first thrombolyzed AMI. The study is a substudy of the DANish Trial in Acute Myocardial Infarction (DANAMI) (n = 1,008) that randomized patients with inducible ischemia after their first AMI, treated with intravenous thrombolytic therapy, to conservative treatment or coronary angiography followed by the appropriate revascularization strategy. A total of 817 patients had complete sets of evaluable electrocardiograms. Electrocardiograms were obtained at randomization, and at 3, 6, and 12 months of follow-up and subjected to blinded core-laboratory evaluation according to the Selvester QRS scoring method. This score considers Q-, R-, and S-wave duration and ratios to provide a semiquantitative estimate of AMI size. The median electrocardiographic estimated infarct size in the entire population was 15% of the left ventricle at randomization. At the end of the follow-up period this estimate had decreased to 12% (p < 0.00001). There was no difference in the rate of QRS resolution whether the patients were subgrouped according to randomization or subgrouped according to actual treatment with or without revascularization. The present study confirms the findings from previous studies conducted in the prethrombolytic era, that considerable normalization of the QRS complex also occurs after AMI treated with thrombolytic therapy. This QRS normalization seems unaffected by an aggressive treatment strategy with revascularization via balloon angioplasty or bypass surgery.

Admission standard electrocardiogram for early risk stratification in patients with unstable coronary artery disease not eligible for acute revascularization therapy: a TRIM substudy. ThRombin Inhibition in Myocardial Infarction.

OBJECTIVES: The purpose of this study was to determine the prognostic capacity of a single electrocardiogram (ECG) obtained early after admission to the hospital in patients suspected of non-Q-wave myocardial infarction and unstable angina pectoris. METHODS: Six hundred twenty-nine patients from the TRIM study were included. The patients were divided into subgroups on the basis of ST-segment changes in the inclusion ECG. Death, acute myocardial infarction, or refractory angina (despite treatment) were registered during a follow-up period of 30 days. RESULTS: Patients with ST depression had a significantly higher event rate compared with patients with other ECG changes or with normal ECG results. The difference in event rates between patients with ST depression and patients without ST depression regarding the composite of death and acute myocardial infarction was highly significant (P =.0008). A significant association between the magnitude of the ST-segment depression (in millimeters) and the risk of cardiac events was also demonstrated. Multivariate analysis proved ST depression early after admission to be an independent predictor of high risk. CONCLUSION: In patients with unstable coronary artery disease, ST-segment depression at admission is a strong predictor of early (30 days) cardiac events and the extent of ST depression carries important prognostic information as well.

Very early risk stratification using combined ECG and biochemical assessment in patients with unstable coronary artery disease (A thrombin inhibition in myocardial ischemia [TRIM] substudy). The TRIM Study Group.

BACKGROUND: The diagnostic capability of troponin T (TnT), troponin I (TnI), myoglobin, and creatine kinase (CK)-MB mass for detection of myocardial injury seems evident. Newer studies have found these sensitive markers to carry independent prognostic information in patients with unstable coronary artery disease as well. ST-segment depression in the admission ECG is known to be an important indicator of poor outcome in these patients. The present study investigates the prognostic capacities of the ECG in combination with biochemical admission measurements in 516 patients admitted to hospital with unstable coronary artery disease. METHODS AND RESULTS: Baseline ECG recordings and blood samples were collected for central analysis. The patients were followed up for 30 days, and predefined end points, ie, death, myocardial infarction, and refractory angina, were registered as end points. By univariate analysis, ST-segment depression, inverted T waves in >/=5 leads, TnT >/=0.1 microg/L, TnI >/=0.5 microg/L, myoglobin >/=40 microg/L, female sex, and age >/=65 years were predictors of death and myocardial infarction at 30 days. By multivariate analysis, female sex, ST-segment depression at randomization, or inverted T-waves in >/=5 leads were the only independent predictors of death or myocardial infarction. On the basis of baseline ECG ST-T changes and CK-MB mass/TnT/TnI/myoglobin levels, the patients were divided into 3 subgroups at high (14% event rate), intermediate (6%), and low (3%) risk of early death/myocardial infarction. CONCLUSIONS: The present study found the combination of baseline values of TnT, TnI, CK-MB mass, and ST-T changes in the ECG to be effective for early risk stratification in patients with unstable coronary artery disease.

Differences between local investigator and core laboratory interpretation of the admission electrocardiogram in patients with unstable angina pectoris or non-Q-wave myocardial infarction (a Thrombin Inhibition in Myocardial Ischemia [TRIM] substudy).

The present study compares the on-site interpretation of an admission electrocardiogram (ECG) with core laboratory results in a large, multicenter trial of 516 patients diagnosed with unstable angina pectoris or non-Q-wave myocardial infarction. The local investigators evaluated the admission ECG regarding ST-T changes before the ECGs were sent to the core laboratory for blinded interpretation. The strength of agreement between the observations was described by kappa statistics. There was a poor agreement regarding identification of ST-segment elevation, with 17 patients identified by the local investigator versus 92 by the core laboratory (kappa = 0.05). There was a fair agreement on ST-segment depression with 158 patients diagnosed on-site versus 64 by the core laboratory (kappa = 0.38). Identification of T-wave inversion demonstrated good agreement with 306 patients diagnosed on-site versus 280 by the core laboratory (kappa = 0.63). A moderate agreement regarding identification of a normal ECG was found with 101 patients on-site versus 135 in the core laboratory (kappa = 0.42). Independent variables, including peak creatine kinase-MB and 30-day outcome, were more closely related to core laboratory results than the local investigator's interpretation of the admission ECG. Thus, in the present study, considerable differences were demonstrated between the on-site interpretation of the admission ECG and the blinded evaluation performed in the core laboratory regarding relatively simple electrocardiographic variables. The results suggest that more widespread use of independent evaluation of clinical data should be incorporated in future clinical trials.

Serial prognostic capabilities of electrocardiographic indices of infarcted and hibernating myocardium in predicting short- and long-term outcome following coronary artery bypass surgery.

The present study was performed to test the hypothesis that patients with a large amount of ischemic (hibernating) myocardium are most likely to develop a perioperative myocardial infarction undergoing coronary artery bypass grafting (CABG). Furthermore, we evaluated the Selvester QRS scoring system as a postoperative prognostic tool. A relationship between a high amount of hibernating myocardium determined by ventriculographic and electrocardiographic investigations and an increased risk of perioperative myocardial infarction was found. The Selvester QRS scoring system used in diagnosing and prognosing after acute myocardial infarction was proven valid in predicting prognosis after CABG as well.

[Thrombocyte aggregation and serum thromboxane B2 in patients with unstable angina pectoris treated with diltiazem or verapamil]. / Trombocytaggregation og serum-tromboxan-B2 hos patienter med ustabil angina pectoris behandlet med diltiazem eller verapamil.

Patients with unstable angina pectoris have increased thrombocyte aggregation and disturbances in serum prostaglandin balance. As a pilot project, we conducted a single-blind investigation of 24 patients with unstable angina pectoris treated with dilthiazem (n = 12, 240-360 mg) or verapamil (n = 12, 240-360 mg) for ten days. At the commencement of the investigation, both patient groups had hyperaggregating thrombocytes and increased serum-thromboxan-B2 (TXB2) as compared to healthy individuals (p < 0.01). In the patient group treated with dilthiazem, the aggregation threshold rose (p < 0.01), and the serum TXB2 values fell to approximately normal (p < 0.05). In the patient group treated with verapamil, no significant changes were observed in the measurements registered. The difference between the two groups remained significant during the entire therapeutic period (p < 0.01). Thus, dilthiazem appears to counteract thrombocyte aggregation in patients with unstable angina pectoris.