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Objectives In this dose-finding study, we sought to compare fondaparinux with enoxaparin in patients with acute coronary syndromes (ACS). Background Fondaparinux is a synthetic pentasaccharide that selectively inhibits activated clotting factor X. It has been demonstrated as effective in preventing thromboembolic complications in orthopedic surgery. Methods Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) and enoxaparin (1 mg/kg twice daily) were compared, both given for three to seven days, in patients with ACS without persistent ST-segment elevation. Results The rates of the combined primary end point of death, myocardial infarction, or recurrent ischemia after nine days were 27.9%, 35.9%, 34.7%, 30.3%, and 35.7% in patients allocated to fondaparinux doses of 2.5, 4, 8, and 12 mg and enoxaparin, respectively (p = NS). In the per-protocol analysis (929 patients who received adequate study drug and had adequate ST-segment monitoring), these figures were 30.0%, 43.5%, 41.0%, 34.8%, and 40.2%. Again, no dose response was observed. The lowest event rates were observed in the 2.5-mg fondaparinux group, which had significantly lower rates than the enoxaparin group as well as for 4 and 8 mg fondaparinux in the per-protocol analysis (p Conclusions This dose-finding study revealed no dose response for different fondaparinux doses ranging from 2.5 to 12 mg subcutaneously and suggests that the efficacy and safety of fondaparinux may be similar to that of enoxaparin. Further studies with fondaparinux in ACS might include the lowest dose (2.5 mg) investigated in this study.

PURPOSE: To investigate the prognostic importance of new small Q waves following an acute coronary syndrome. METHODS: We assessed 6-month mortality in 10,501 patients with non-ST-elevation acute coronary syndromes who had survived 30 days and had both admission and 30-day electrocardiograms. Patients were stratified by whether they had no new Q waves (n = 9447), new 30- to 40-ms Q waves (n = 733), or new ≥40-ms Q waves (n = 321). RESULTS: Mortality was higher in patients with 30- to 40-ms Q waves than in those with no new Q waves (3.4% [25/733] vs. 2.4% [227/9447], P = 0.005), and even higher in those with ≥40-ms Q waves (5.3% [17/321], P = 0.002). After adjustment for baseline risk predictors, mortality remained higher in patients with new 30- to 40-ms Q waves (odds ratio [OR] = 1.30; 95% confidence interval [CI]: 0.85 to 1.98; P = 0.23) and those with new ≥40-ms Q waves (OR = 1.87; 95% CI: 1.13 to 3.09; P = 0.01). CONCLUSION: Patients with new small Q waves following a non-ST-elevation acute coronary syndrome are at increased risk of adverse outcomes. These small Q waves should be considered diagnostic of myocardial infarction. Further research should investigate whether even smaller QRS changes are prognostically important.

OBJECTIVES: Currently, the interatrial septum (IAS) pacing site is indirectly selected by fluoroscopy and P-wave analysis. The aim of the present study was to develop a novel approach for IAS pacing using intracardiac echocardiography (ICE). BACKGROUND: Interatrial septum pacing may be beneficial for the prevention of paroxysmal atrial fibrillation. METHODS: Cross-sectional images are acquired during a pull-back of the ICE transducer from the superior vena cava into the inferior vena cava by an electrocardiogram- and respiration-gated technique. Both atria are then reconstructed using three-dimensional (3D) imaging. Using an "en face" view of the IAS, the desired pacing site is selected. Following lead placement and electrical testing, another 3D reconstruction is performed to verify the final lead position. RESULTS: Twelve patients were included in this study. The IAS pacing was achieved in all patients including six suprafossal (SF) and six infrafossal (IF) lead locations all confirmed by 3D imaging. The mean duration times of a trial lead implantation and fluoroscopy were 70 ± 48.9 min and 23.7 ± 20.6 min, respectively. The IAS pacing resulted in a significant reduction of the P-wave duration as compared to sinus rhythm (98.9 ± 19.3 ms vs. 141.3 ± 8.6 ms; p < 0.002). The SF pacing showed a greater reduction of the P-wave duration than IF pacing (59.4 ± 6.6 ms vs. 30.2 ± 13.6 ms; p < 0.004). CONCLUSIONS: Three-dimensional ICE is a feasible tool for guiding IAS pacing.

Computer-assisted continuous monitoring of the ST-segment allows detection and quantification of recurrent ischemia in patients with acute coronary syndromes. In a substudy of the PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial, this technique was used to evaluate the effects of the glycoprotein IIb/IIIa inhibitor eptifibatide on the incidence and severity of recurrent ischemia, and to investigate the relationship between recurrent ischemia and the occurrence of subsequent death or myocardial (re)infarction. A total of 258 patients with unstable angina or evolving myocardial infarction without ST elevation were monitored for 24 hours during infusion with either eptifibatide or placebo with a computer-assisted 12-lead ECG-ischemia monitoring device. Recurrent ischemic episodes were identified by an automated computer algorithm. Two hundred and sixteen patients (84%) had ECG recordings suitable for analysis. Ischemic episodes were detected in 35 (33%) of the 105 eptifibatide patients and in 32 (29%) of the 111 placebo patients (not significant). No difference in ischemic burden was apparent between both treatment groups. Patients who exhibited 2 or more episodes of recurrent ischemia more frequently died or suffered a myocardial infarction, both at 7 and 30 days, as well as through the 6-month follow-up. A greater ischemic burden was significantly related to adverse outcome during the 6-month follow-up period. Real-time computer-assisted continuous multilead ECG-ischemia monitoring may help to identify patients with unstable coronary syndromes at increased risk of adverse outcome and, thus, allow for better prognostic triage and more appropriate selection of therapeutic strategies. Integration of these systems in coronary care units and emergency wards should, therefore, be recommended.

Pericardial effusion may originate from a wide variety of underlying pathology. Primary cardiac malignancy should always be considered as a rare underlying cause. Angiosarcoma is the most common cardiac malignancy, which often arises as a mass in the right atrium. We describe a young patient with collapse due to pericardial effusion caused by a primary cardiac angiosarcoma. The case is an example of the difficulties and dilemmas which may be encountered in assessing the diagnosis of cardiac angiosarcoma. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Background The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. Methods and Results The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of α-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST-trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. Conclusions These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy. (Am Heart J 1999;138:525-32.)

I n t r o d u c t i o n Evaluation of patients admitted with acute chest pain is time consuming and expensive, while a substantial proportion of these patients do not really suffer from an acute coronary syndrome (ACS). 1'2 Risk stratification usually takes place in the emergency room and its primary aim is to identify or exclude life-threatening conditions such as myocardial infarction or unstable angina. The traditional approach to the assessment of patients with suspected acute coronary syndrome is based on three criteria: assessment of clinical symptoms, electrocardiographic findings on admission electrocardiogram (ECG), and measurements of biochemical markers.

Objectives. We sought to study the relation between recurrent ST segment shift within 6 to 24 h of initial resolution of ST elevation after thrombolytic therapy and 30-day and 1-year mortality. Background. Rapid and stable resolution of ST segment elevation in relation to thrombolytic therapy in patients with an acute myocardial infarction is an indicator of culprit artery patency. Whether recurrence of ST segment shift during continuous ST monitoring after initial resolution is related to poor prognosis has not been studied. Methods. ST segment monitoring was performed within 30 min after thrombolytic therapy for acute myocardial infarction. The predictive value of a new ST segment shift (assessed as ≥0.1-mV deviation from the baseline) 6 to 24 h after thrombolytic therapy was studied with respect to 30-day and 1-year mortality. Results. Of 734 patients, 243 had a new ST segment shift (33%). The 30-day mortality rate in patients with an ST shift (7.8%) was significantly higher than that in patients without an ST shift (2.25%, p = 0.001), as was the 1-year mortality rate (10.3% vs. 5.7%, respectively, p = 0.025). Multivariable analysis revealed an independent predictive value of ST shift with respect to 30-day mortality (p = 0.008), even after consideration of multiple clinical risk factors in the overall Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO)-I mortality model (p = 0.0001). Moreover, the duration of the ST shift bore a direct relation with 1-year mortality (p = 0.008). Conclusions. Detection of ST segment shift early after thrombolytic therapy for acute myocardial infarction is a simple, noninvasive means of identifying patients at high risk and is superior to other commonly assessed clinical risk factors. Thus, patients with a new ST shift after the first 6 h, but within 24 h, represent a high risk group that may benefit from more aggressive intervention, whereas patients without evidence of an ST shift represent a low risk subgroup.

The selection of ECG leads used for ST monitoring may influence detection and quantitation of ischaemia.We compared on-line continuous 48-h 12-lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI-100). Onset and offset of ST episodes were defined by the lead with the firstor = 100 microV ST change relative to baseline and the lead with the latest return to baseline ST level, respectively. ST episodes were calculated for 12 leads and 3 leads (V2, V5, III) separately.ST episodes were detected in 88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead and 2 (1.6) for 12-lead (P0.0001). The total duration of ischaemia detected during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3) min respectively (P0.0001). The probability of recurrent ischaemia declined most during the first 24 h of monitoring. After a period without ST changes of 1, 12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%, respectively.Continuous 12-lead ST monitoring increases detection rate and duration of ST episodes compared to 3-lead ST monitoring. The use of continuous 12-lead ECG monitoring devices on emergency wards and coronary care units is recommended.

Low heart rate variability is associated with high risk of sudden death in myocardial infarction patients. This has been attributed to unfavorable autonomic cardiac control. In the present study, the predictive value of heart rate variability for sudden death, mortality from coronary heart disease, and from all causes was investigated in the general population, using brief electrocardiographic recordings. From 1960 to 1985, 878 middle-aged Dutch men, aged 40-60 years, were followed and repeatedly examined as part of the Zutphen Study. In 1985 the remaining cohort was extended to 885 elderly men, aged 65-85 years, and followed until 1990. Heart rate variability (standard deviation of duration of normal RR intervals) was determined from the resting 12-lead electrocardiogram. The 5-year age-adjusted relative rate of total mortality of men with heart rate variability of < 20 milliseconds (msec) compared with men with heart rate variability of 20-39 msec was 2.1 (95 percent confidence interval 1.4-3.0) in middle-aged men and 1.4 (95% confidence interval 0.9-2.2) in elderly men. Death from noncoronary causes, especially cancer, contributed significantly to this elevated risk. The association of low heart rate variability with sudden death or coronary heart disease mortality was less consistent. In conclusion, in middle-aged men and probably in elderly men, low heart rate variability is predictive of mortality from all causes. This suggests that low heart rate variability is an indicator of compromised health in the general population.

OBJECTIVE: Reperfusion of the infarct-related artery in patients with acute myocardial infarction limits infarct size, but also causes accelerated release into plasma of cardiac tissue proteins. The latter effect could reflect either enhanced protein washout from the heart or abrupt disruption of myocyte membranes. The present study indicates that the latter mechanism prevails. METHODS: In 26 patients, patency of the infarct-related artery was determined by coronary angiography 90 min and 5-7 days after thrombolytic treatment. Continuous electrocardiography was performed during the first 24 h after admission. Cumulative release of myoglobin (Mb) and creatine kinase (CK) into plasma was calculated from frequently sampled plasma concentrations. RESULTS: In patients with a patent infarct-related artery after 90 min, onset of a rapid (> 50%) decrease in ST-vector magnitude coincided with an equally rapid increase in QRS-vector magnitude, and with a sudden onset of release into plasma of Mb as well as CK. In these patients, a maximal initial release rate was observed and cumulative release conformed closely to a simple model for sudden interstitial liberation of proteins. In contrast, protein release started more gradually and could not be fitted to this model, in patients with persistent occlusion of the infarct-related artery at 90 min and absence of ST-vector normalisation. CONCLUSIONS: Previous studies have demonstrated significant myocardial salvage by timely reperfusion therapy. Nevertheless, this study indicates that the moment of recanalisation of the infarct-related artery coincides with sudden and massive disruption of myocyte membranes. Attenuation of this effect, if possible, could further improve the benefits of reperfusion therapy.

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems. Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were performed as a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up to the time of angiography. Predictive values at 90 and 180 min after the start of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion, respectively. In retrospect, accuracy appeared greatest (79-100%) in patients with extensive ST segment elevation (> or = 400 microV), if both speed of ST recovery and extent of ST segment elevation were taken into account. Although the three recording systems differed considerably in signal processing, no significant difference in accuracy was demonstrated among these systems. We conclude that continuous ECG monitoring may help select high risk patients without apparent reperfusion who may benefit from additional reperfusion therapy. As ST recovery may occur early after the start of thrombolytics and accuracy of the test is related to peak ST levels, the use of on-line ECG monitoring devices on emergency wards and cardiac care units is recommended.

The clinical significance of ST-segment changes and of the time course of appearance in serum of different cardiac proteins has been reviewed for the diagnosis of coronary reperfusion and reocclusion after thrombolysis. In particular, the value of serial 12-lead electrocardiographic (ECG) studies, of Holter monitoring, and of continuous multilead computer-assisted ECG monitoring is compared. Regarding the serum proteins, the clinical significance of reperfusion indices described so far for serum creatine kinase (CK), its isoenzyme serum creatinine kinase MB, the CK isoforms, and myoglobin is reviewed. Emphasis is placed on (1) the calculation method used for deriving the reperfusion indices; (2) the sensitivity and the specificity of the reperfusion indices; (3) the minimum turn-around time needed to produce the reperfusion indices (depending on the practicability of the analytical and calculation methods and their applicability in an emergency laboratory); (4) the ability of the indices to produce reliable estimates of reperfusion efficacy of the thrombolytic agents under study; and (5) the ability of the marker proteins to detect reinfarction as well as the suitability of the markers to detect real-time necrosis.

The European Society of Cardiology and American College of Cardiology established their initial Joint Consensus Conference in July 1999 to develop a new definition of Acute Myocardial Infarction. This action was deemed necessary because of the development of new sensitive biochemical markers of myocardial necroses: Troponins T and I. There were 5 working groups, including one in Electrocardiography. The Conference adopted a definition that required only a history of "ischemic symptoms" and "a typical rise and fall" of at least one of the biochemical markers. The ECG Working Group strongly advised that a term distinctive from "myocardial infarction" such as "myocardial necrosette" be adopted as the diagnosis for an acute coronary event during which the peak biochemical marker level is below that which occurs when serial evolutionary ECG changes are observed. A pilot substudy from the GUSTO IIa Clinical Trial has identified the low end of the "ECG Change Range" to be: >2x the upper limit of normal for CK-MB, > 11 x for Troponin T, and >6 x for Troponin I.

Background— Adverse perioperative cardiac events occur frequently despite the use of beta (β)-blockers. We examined whether higher doses of β-blockers and tight heart rate control were associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome. Methods and Results— In an observational cohort study, 272 vascular surgery patients were preoperatively screened for cardiac risk factors and β-blocker dose. Beta-blocker dose was converted to a percentage of maximum recommended therapeutic dose. Heart rate and ischemic episodes were recorded by continuous 12-lead electrocardiography, starting 1 day before to 2 days after surgery. Serial troponin T levels were measured after surgery. All-cause mortality was noted during follow-up. Myocardial ischemia was detected in 85 of 272 (31%) patients and troponin T release in 44 of 272 (16.2%). Long-term mortality occurred in 66 of 272 (24.2%) patients. In multivariate analysis, higher β-blocker doses (per 10% increase) were significantly associated with a lower incidence of myocardial ischemia (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.51 to 0.75), troponin T release (HR, 0.63; 95% CI, 0.49 to 0.80), and long-term mortality (HR, 0.86; 95% CI, 0.76 to 0.97). Higher heart rates during electrocardiographic monitoring (per 10-bpm increase) were significantly associated with an increased incidence of myocardial ischemia (HR, 2.49; 95% CI, 1.79 to 3.48), troponin T release (HR, 1.53; 95% CI, 1.16 to 2.03), and long-term mortality (HR, 1.42; 95% CI, 1.14 to 1.76). Conclusion— This study showed that higher doses of β-blockers and tight heart rate control are associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome in vascular surgery patients.

An application "Pocket WinView" was developed for a Pocket PC personal digital assistant device, which allows remote access to near real-time physiological information from a patient monitor on a commercial handheld device (iPAQ, Pocket PC). The application provides continuous display of up to six monitored physiological waveforms and parameter values. Wireless communication can be established using Wireless LAN and general packet radio service (GPRS). Data is protected with hybrid public key encryption. User authentication is required every time the application is started. Patient data can also be stored on Compact Flash memory cards for data collection purposes. Additional integration with Web-based applications on the hospital intranet make it possible to combine the near realtime signals with previously recorded 12-lead ECGs, laboratory test results, and charting information.

In this dose-finding study, we sought to compare fondaparinux with enoxaparin in patients with acute coronary syndromes (ACS).Fondaparinux is a synthetic pentasaccharide that selectively inhibits activated clotting factor X. It has been demonstrated as effective in preventing thromboembolic complications in orthopedic surgery.Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) and enoxaparin (1 mg/kg twice daily) were compared, both given for three to seven days, in patients with ACS without persistent ST-segment elevation.The rates of the combined primary end point of death, myocardial infarction, or recurrent ischemia after nine days were 27.9%, 35.9%, 34.7%, 30.3%, and 35.7% in patients allocated to fondaparinux doses of 2.5, 4, 8, and 12 mg and enoxaparin, respectively (p = NS). In the per-protocol analysis (929 patients who received adequate study drug and had adequate ST-segment monitoring), these figures were 30.0%, 43.5%, 41.0%, 34.8%, and 40.2%. Again, no dose response was observed. The lowest event rates were observed in the 2.5-mg fondaparinux group, which had significantly lower rates than the enoxaparin group as well as for 4 and 8 mg fondaparinux in the per-protocol analysis (p0.05). Bleeding rates were low and not different among the patient groups. No differences were observed in fondaparinux concentrations in patients with or without death, myocardial infarction, recurrent ischemia, or bleeding events.This dose-finding study revealed no dose response for different fondaparinux doses ranging from 2.5 to 12 mg subcutaneously and suggests that the efficacy and safety of fondaparinux may be similar to that of enoxaparin. Further studies with fondaparinux in ACS might include the lowest dose (2.5 mg) investigated in this study.

Objective: To compare the efficacy of cardioversion in patients with atrial fibrillation between monophasic damped sine waveform and rectilinear biphasic waveform shocks at a high initial energy level and with a conventional paddle position. Design: Prospective randomised study. Patients and setting: 227 patients admitted for cardioversion of atrial fibrillation to a tertiary referral centre. Results: 70% of 109 patients treated with an initial 200 J monophasic shock were cardioverted to sinus rhythm, compared with 80% of 118 patients treated with an initial 120 J biphasic shock (NS). After the second shock (360 J monophasic or 200 J biphasic), 90% of the patients were in sinus rhythm in both groups. The mean cumulative energy used for successful cardioversion was 306 J for monophasic shocks and 159 J for biphasic shocks (p < 0.001). Conclusions: A protocol using monophasic waveform shocks in a 200–360 J sequence has the same efficacy (90%) as a protocol using rectilinear biphasic waveform shocks in a 120–200 J sequence. This equal efficacy is achieved with a significantly lower mean delivered energy level using the rectilinear biphasic shock waveform. The potential advantage of lower energy delivery for cardioversion of atrial fibrillation needs further study.

It is well known that changes in the body position (BPC) can have marked changes on the electrical axis of the heart. This may cause ST-segment shifts and/or T-wave inversions, triggering false alarms during continuous ECG monitoring. To investigate the effects in the CCU setting, a body position test (BPT) has been set up to measure the effect during controlled BPC. The ECG obtained in the supine position was used as reference. A scalar and spatial approaches were used. The scalar approach uses linear regression analysis, the supine position being the reference mapping all measurements to the supine position. The spatial approach uses the derived VCG by applying the inverse Dower transformation. This paper describes the results of the first 54 patients done so far. Marked ST-changes (>100 /spl mu/V) were observed in 11 patients out of the 54 when turning to their left side. Other positions appear to have much less effect. A concomitant axis shift in the frontal plane of more than 15 degrees was present in 5 of these 11 patients with ST-changes. Two patients showed T-wave inversion when turning from supine to the left side.

An academic 12-lead electrocardiogram (ECG) core laboratory aims to provide the highest possible quality ECG recording, measurement, and storage to aid clinicians in research into important cardiovascular outcomes and to maximize the credibility of scientific results based solely, or in part, on ECG data. This position paper presents a guide for the structure and function of an academic ECG core laboratory. The key functional aspects are: 1) Data collection, 2) Staff composition, 3) Diagnostic measurement and definition standards, 4) Data management, 5) Academic considerations, 6) Economic consideration, and 7) Accreditation. An ECG Core Laboratory has the responsibility for rapid and accurate analysis and responsible management of the electrocardiographic data in multicenter clinical trials. Academic Laboratories, in addition, provide leadership in research protocol generation and production of research manuscripts for submission to the appropriate peer-review journals.

Aims Recurrent ischaemia, detected by continuous ECG monitoring, in patients with unstable angina increases the risk of unfavourable outcome. Studies that evaluated this relationship have been limited by the small series of patients. By combining data from three studies, the present analysis aims to provide an accurate assessment of the impact of recurrent ischaemia detected by multilead ECG-ischaemia monitoring on the occurrence of death and myocardial infarction in patients with acute coronary syndromes. Methods and Results Data were obtained from CAPTURE, PURSUIT and FROST, three trials evaluating glycoprotein IIb/IIIa blockers in patients with non-ST-elevation acute coronary syndromes. Patients were monitored for 24h after enrolment with a computer-assisted 12-lead or a vectorcardiographic ECG–ischaemia monitoring device. In a retrospective blinded analysis, recurrent ischaemic episodes were identified by a computer algorithm. The number of ischaemic episodes was normalized to 24h. Ischaemic episodes were detected in 271 (27%) of 995 patients. There was a direct proportional relationship between the number of ischaemic episodes per 24h and the probability of cardiac events at 5 and 30 days. The 30-day composite of death and myocardial infarction occurred in 5·7% of patients without episodes and increased to 19·7% in patients with ≥5 episodes. After adjustment for baseline predictors of adverse outcome, the relative risk of death or myocardial infarction at 5 and 30 days increased by 25% for each additional ischaemic episode per 24h. Conclusions This analysis emphasizes the need for integration of multilead ECG–ischaemia monitoring systems in coronary care units and emergency wards to improve early risk stratification in patients with acute coronary syndromes.

Aims Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and eYcacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. Methods Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0·105 mg . kg "1 .h "1 to 1·2 mg . kg "1 .h "1 over 48 h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. EYcacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. Results Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1·2 mg . kg "1 .h "1 resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant diVerences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients. Conclusion Administration of efegatran sulphate at levels of at least 0·63 mg . kg "1 .h "1 provided an antithrombotic eVect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent. (Eur Heart J 1999; 20: 1101‐1111)

Decreased heart rate variability has been associated with an adverse prognosis in patients after myocardial infarction. Studies carried out in the population at large show contradictory results. The authors examined the association between heart rate variability on a standard 10-second electrocardiogram and cardiac and all-cause mortality in the Rotterdam Study, a population-based cohort study of men and women aged > or =55 years, using data collected between 1990 and 1996 (mean follow-up = 4 years). Heart rate variability, taken as the standard deviation of normal R-R intervals (SDNN), was computed by means of the Modular ECG Analysis System. After exclusion of subjects with arrhythmia and those with fewer than six normal R-R intervals, the study population consisted of 2,088 men and 3,184 women. Cox's proportional hazards model was used to examine the age- and sex-adjusted risk for cardiac, noncardiac, and total mortality in relation to quartiles of SDNN, using the third quartile of SDNN as the reference category. Subjects in the lowest quartile of SDNN relative to those in the third quartile had an 80 percent age- and sex-adjusted increased risk for cardiac mortality (hazard ratio = 1.8; 95% confidence interval: 1.0, 3.2). Interestingly, for subjects in the highest quartile of SDNN, an even more pronounced risk for cardiac mortality was present (hazard ratio = 2.3; 95% confidence interval: 1.3, 4.0). Additional adjustment for possible confounders did not materially change the risk estimates. The authors conclude that heart rate variability measured on the standard 10-second electrocardiogram can be used to identify older men and women with an increased risk for cardiac mortality. In the elderly, increased heart rate variability is an even stronger indicator of cardiac mortality than decreased heart rate variability. Further studies are needed to confirm these findings and to elucidate their physiologic meaning.

The Cardiac Infarction Injury Score (CIIS) is an electrocardiographic classification system that was developed as a diagnostic tool to assess the extent of cardiac injury in acute myocardial infarction. We investigated the prognostic value of the CIIS in post-myocardial infarction patients.The prognostic values of the CIIS for total and cardiac mortality was assessed in a large series (n = 3395) of patients who were enrolled in the ASPECT trial. Standard 12-lead electrocardiograms, recorded prior to hospital discharge were coded according to the CIIS and the Minnesota Code. Mean CIIS was 26 (range--8 to 59). After adjustment for other baseline characteristics, the CIIS was directly related to the risk of total mortality and cardiac mortality. At one-year follow-up the relative risks of CIISor = 40, CIIS 30-40 and CIIS 20-30 were significantly higher than in those with a CIIS20. The relative risks were, respectively, 2.3 (1.2-4.4), 2.2 (1.3-3.9) and 1.6 (0.9-2.9). At 3 year follow-up, the relative risks were, respectively, 2.1 (1.4-3.2), 1.7 (1.2-2.4) and 1.5 (1.0-2.1). The relative risks for total mortality were similar. When patients with major ECG abnormalities, as defined by the Minnesota code, were excluded, the associations were still significant in the CIIS classes 30-40 and40.The CIIS ECG scoring system is an important predictor for long-term cardiac mortality in post myocardial infarction patients. It can easily be automated and is efficient for classifying cardiac injury in epidemiological studies.

Background —In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. Methods and Results —Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had ≥2 ST episodes ( P P Conclusions —Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.

Prolongation of heart rate-adjusted QT length (corrected QT interval [QTc]) is associated with elevated risk of coronary heart disease and sudden death. This may have to do with autonomic cardiac control. Because insulin is known to stimulate sympathetic activity, we studied the association of insulin level and glucose tolerance with QTc. In 1990, 383 elderly men 70–89 years of age without previous myocardial infarctions or known diabetes had a 12-lead electrocardiogram recorded and glucose tolerance determined in the frame of an ongoing follow-up study. QTc was significantly associated with fasting glucose, insulin, and C-peptide and glucose levels 60 and 120 min after an oral glucose load. For fasting C-peptide and the area under the glucose curve (AUGC), this association could not be explained by the concomitant occurrence of other risk factors of coronary heart disease. Furthermore, fasting C-peptide and the AUGC were independently additive predictors of QTc duration. The difference in QTc between men in the extreme quintiles of both variables was 22 ms. QTc prolongation seems to be part of the insulin resistance syndrome. The association may be explained by increased sympathetic activity induced by high insulin levels. An additional explanation could be an effect of high insulin, impaired glucose utilization, or both on membrane activity of myocardial cells.

The Cardiac Infarction Injury Score (CIIS), based on electrocardiographic characteristics, was developed as a measure to determine the presence of myocardial infarctions. In the present study the association of the CIIS with coronary morbidity and mortality was investigated among middle-aged and elderly men. A cohort of 877 men, born between 1900 and 1919, was followed and repeatedly examined from 1960 onwards. In 1985 the remaining cohort was extended to 836 elderly men from the same birth cohort, and followed until 1990. In both middle-aged and elderly men with high CIIS the prevalence of (silent) previous myocardial infarction and the occurrence of ST-T abnormalities were increased. Five-year relative risks of men with CIIS 20 or more relative to men with CIIS5 were 2.2 (95% confidence interval: 1.2-4.1) for angina pectoris, 2.4 (1.4-4.0) for myocardial infarction and 5.8 (3.4-9.9) for coronary heart disease death. Thus, the CIIS is associated with risk of coronary heart disease in apparently healthy middle-aged as well as elderly men.

Objectives. This study evaluated the predictive value of T wave amplitude and ST segment level on lead I for angina pectoris, a first myocardial infarction, sudden death and coronary heart disease death in middle-aged and elderly men. Background. Certain ST-T wave characteristics may reflect favorable autonomic cardiac control. Slight ST segment elevation has been reported to indicate a low risk of coronary heart disease mortality. Methods. A total of 876 men, born between 1900 and 1920, participated in periodic medical examinations and were followed up with respect to morbidity and mortality from 1960 to 1985. In 1985, the remaining cohort was extended to 836 elderly men from the same birth cohort who were followed up until 1990. Relative risks in categories of T wave amplitude and ST segment level were estimated by survival analysis. Results. Both middle-aged and elderly men with T wave amplitudes ≥0.15 mV had a lower risk of myocardial infarction, coronary heart disease death and sudden death than men with T wave amplitudes 0.05 to 0.15 mV. The adjusted relative risk of coronary heart disease death was 0.5 (95% confidence interval [CI] 0.2 to 1.0); in men with T wave amplitude ≤0.05 mV, relative risk was 2.0 (95% CI 1.3 to 3.1). Slight ST segment elevation was also associated with decreased risk: relative risk 0.5 (95% CI 0.3 to 1.0) compared with the isoelectric ST segment level. In men with ST segment depression, relative risk was 2.2 (95% CI 1.4 to 3.4). The associations of T wave amplitude and ST segment level were independent of each other. Conclusions. In addition to the elevated risk of coronary heart disease that is associated with ST-T wave abnormalities, we observed that normal variations in repolarization characteristics are predictive of future heart disease.

BACKGROUND Heart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men. METHODS AND RESULTS From 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Age-adjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors. CONCLUSIONS These results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.

A65-year-old woman complained of nocturnal dyspnea, a period of stabbing pain between the shoulder blades, and swollen ankles that had persisted for 3 days. Physical examination revealed an irregular heart rate of 120 bpm; a blood pressure of 140/90 mm Hg in both arms; basal crepitations over both lungs; a grade 3/6 diastolic murmur maximal at the left sternal border; no abnormalities of the abdominal region; normal pulses of the radial, femoral, and carotid arteries; and ankle edema. An ECG showed atrial flutter with variable ventricular response and normal QRS-T complexes. Complete blood cell count, renal and hepatic function tests, and serological studies gave normal results. Chest radiograph showed an enlarged heart, an elongated aorta, normal lungs, and thoracic kyphosis. Transthoracic …

One hundred patients with sporadically occurring symptoms suggesting cardiac arrhythmias were evaluated with the aid of a transtelephonic electrocardiographic recording device (Cardiomemo). In 83 patients, 124 episodes with symptoms were documented and a correlation with electrocardiographic findings could be established. Forty of these patients (48%) had a cardiac arrhythmia and 43 (52%) had a normal heart rhythm. It appears that, for the assessment of sporadically occurring symptoms, transtelephonic electrocardiographic recording is a valuable supplement to 24-hour ambulatory electrocardiographic monitoring.