Peter Klootwijk

Myocardial infarction redefined - A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee f or the redefinition of myocardial infarction

This document was developed by a consensus conference initiated by Kristian Thygesen, MD, and Joseph S. Alpert, MD, after formal approval by Lars Rydén, MD, President of the European Society of Cardiology (ESC), and Arthur Garson, MD, President of the American College of Cardiology (ACC). All of the participants were selected for their expertise in the field they represented, with approximately one-half of the participants selected from each organization. Participants were instructed to review the scientific evidence in their area of expertise and to attend the consensus conference with prepared remarks. The first draft of the document was prepared during the consensus conference itself. Sources of funding appear in Appendix A. The recommendations made in this document represent the attitudes and opinions of the participants at the time of the conference, and these recommendations were revised subsequently. The conclusions reached will undoubtedly need to be revised as new scientific evidence becomes available. This document has been reviewed by members of the ESC Committee for Scientific and Clinical Initiatives and by members of the Board of the ESC who approved the document on April 15, 2000.*

Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study.

BackgroundHeart-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 ResultsFrom 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. Ageadjusted 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. ConclusionsThese 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.

High-Dose β-Blockers and Tight Heart Rate Control Reduce Myocardial Ischemia and Troponin T Release in Vascular Surgery Patients

Background— Adverse perioperative cardiac events occur frequently despite the use of beta (&bgr;)-blockers. We examined whether higher doses of &bgr;-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 &bgr;-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 &bgr;-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 &bgr;-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.

QTc duration is associated with levels of insulin and glucose intolerance. The Zutphen elderly study.

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.

Reduction of Recurrent Ischemia With Abciximab During Continuous ECG-Ischemia Monitoring in Patients With Unstable Angina Refractory to Standard Treatment (CAPTURE)

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<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. 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.

Prognostic significance of ST segment shift early after resolution of ST elevation in patients with myocardial infarction treated with thrombolytic therapy: the GUSTO-I ST Segment Monitoring Substudy.

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 > or = 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.

Comparison of monophasic and biphasic shocks for transthoracic cardioversion of atrial fibrillation

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.

ST segment and T wave characteristics as indicators of coronary heart disease risk: The Zutphen study

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 > or = 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 < or = 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 association 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.

Noninvasive assessment of reperfusion and reocclusion after thrombolysis in acute myocardial infarction

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.

Significance of Acute versus Chronic Troponin T Elevation in Dialysis Patients

Introduction: Cardiac troponin T (cTnT) is often elevated in hemodialysis (HD) patients without acute coronary syndrome (ACS). The aim was to assess the predictive value for mortality of pre-dialysis cTnT in asymptomatic patients. If patients became symptomatic during follow-up, cTnT was followed to assess its diagnostic value for ACS. Methods: Forty-nine asymptomatic HD patients were included: 30 patients with a history of cardiovascular disease (CV+) and 19 without (CV–). In 11 patients cTnT, myoglobin and creatine kinase (CK) were measured before and during HD. During ACS, cTnT was followed until recovery. A cTnT of ≧0.03 µg/l was considered elevated. Follow-up was 2 years. Results: cTnT was elevated in 82% (40/49). More CV+ patients had an elevated cTnT (28/30) than CV– patients (12/19; p = 0.02). There was no change in cTnT, myoglobin and CK during HD. During ACS, cTnT increased above baseline, and tended to return to baseline after recovery. Mortality was 33% (16/49). Patients with elevated cTnT had a higher mortality rate (16/40) than patients with negative cTnT (0/9; p = 0.02). Conclusions: Elevated cTnT levels in asymptomatic HD patients are not caused by acute myocardial injury or by HD itself. They may be related to chronic myocardial damage and decreased clearance, and are of prognostic value. During ACS, however, a cTnT rise above the individual baseline is diagnostic of acute myocardial injury.