Rüdiger Dissmann

Extent of Early ST Segment Elevation Resolution: A Simple but Strong Predictor of Outcome in Patients With Acute Myocardial Infarction

OBJECTIVES This study proposed to verify the prognostic power of early ST segment elevation resolution in patients with acute myocardial infarction from the Intravenous Streptokinase in Acute Myocardial Infarction study data base. BACKGROUND Data from a small prospective study suggested that use of two cutoff points for three different levels of ST segment resolution 3 h after the start of thrombolysis may be an efficient way to predict outcome in an individual patient. METHODS The three groups of ST segment resolution were defined as 1) complete resolution (> or = 70% [552 patients]) or only slight ST segment elevation (127 patients); 2) partial resolution (< 70% to 30% [475 patients]); 3) no resolution (< 30% to > 0% [362 patients]). Infarct size was measured from creatine kinase isoenzyme, MB fraction, release and from the number of Q waves. Left ventricular function was assessed in 818 patients 1 month after infarction. RESULTS For complete, partial and no ST segment resolution 3 h after the start of streptokinase or placebo infusion, enzyme release was 1.2, 1.8 and 2.1 IU/ml x h; number of Q waves 1.7, 2.5 and 3.0; and ejection fraction 60%, 53% and 49%, respectively (all adjusted p = 0.0000). Mortality rate at 21 days was 2.2%, 3.4% and 8.6%, respectively. No ST segment resolution was the most powerful independent predictor of early mortality (p = 0.0001). Survival rate curves at 6-year follow-up showed significant mortality differences with increasing divergence (p = 0.0003 anterior infarction; p = 0.005 inferior infarction). In subgroups with an overall higher risk of dying, mortality was strongly determined by the extent of early ST segment resolution. CONCLUSIONS The extent of ST segment elevation resolution conveys useful early information about outcome in an individual patient after acute myocardial infarction.

Extent of early ST segment elevation resolution: A strong predictor of outcome in patients with acute myocardial infarction and a sensitive measure to compare thrombolytic regimens: A substudy of the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial

OBJECTIVES This study was undertaken to assess prospectively the prognostic power of early ST segment elevation resolution in a large cohort of patients with myocardial infarction and to test the value of differences in ST segment resolution as a surrogate end point. BACKGROUND Previous studies revealed that the use of two cutoff points for three groups of ST segment resolution within 3 h after the start of thrombolysis is most effective in predicting outcome. METHODS The International Joint Efficacy Comparison of Thrombolytics (INJECT) trial compared mortality in 6,010 patients randomized to receive either reteplase or streptokinase. The 1,909 German patients form the basis of this substudy. The three groups of ST segment resolution were defined as complete (> or = 70%), partial (70% to 30%) and no resolution (< 30% to > or = 0%). RESULTS In 1,398 patients presenting < or = 6 h from onset of acute myocardial infarction, the 35-day mortality rate for complete, partial and no ST segment resolution was 2.5%, 4.3% and 17.5%, respectively (p < 0.0001). Peak creatine kinase levels (fraction of normal) were 9.8, 13.4 and 14.0, respectively (p < 0.0001). When baseline characteristics were included, ST segment resolution was the most powerful independent predictor of 35-day mortality. The proportion of patients with complete ST segment resolution was larger, and that with no ST segment resolution smaller, with reteplase than with streptokinase (p = 0.006). CONCLUSIONS No ST segment resolution, indicating failed thrombolysis, predicts very high early mortality, whereas complete resolution is associated with a small infarct area and low mortality. Partial ST segment resolution also predicts larger infarct areas, but early mortality is relatively low. Different extents of ST segment resolution may serve as a sensitive surrogate end point in clinical trials.

Circadian variation of sustained ventricular tachyarrhythmias terminated by appropriate shocks in patients with an implantable cardioverter defibrillator

To determine the circadian variation of sustained ventricular tachyarrhythmias, 78 consecutive patients with an implanted cardioverter defibrillator were analyzed with regard to the occurrence of spontaneous shock episodes during a mean follow-up period of 18 +/- 12 months. In 39 patients 207 shock episodes that terminated potentially life-threatening ventricular tachyarrhythmias could be related to an exact time of onset. A circadian variation (p < 0.001) of these events was demonstrated, with a primary morning peak between 7 hours and 11 hours and a secondary, much smaller peak between 16 hours and 20 hours. This finding indicates the relevance of endogeneous or exogeneous triggers in the cause of malignant arrhythmias that potentially lead to sudden cardiac death. Subgroup analyses revealed an association of the circadian pattern to the New York Heart Association functional classification, indicating perhaps a different role of triggers in different patient populations.

Risk stratification following myocardial infarction in the thrombolytic era: a two-step strategy using noninvasive and invasive methods☆

OBJECTIVES We prospectively performed a two-step risk assessment in patients in the early phase after acute myocardial infarction (MI). BACKGROUND Noninvasive methods like Holter electrocardiographic monitoring (HM) and determination of the left ventricular ejection fraction (EF) as well as the invasive technique of programmed ventricular stimulation (PVS) have been used to identify patients in the late phase after MI as candidates for prophylactic implantation of a cardioverter/defibrillator. However, it is unclear whether these results can be transferred to patients following acute MI. METHODS A series of 657 patients with acute MI (< or = 75 years) underwent HM and EF. If one of the two methods yielded abnormal findings (HM > or = 20 ventricular ectopic beats/h/> or =10 ventricular pairs/day/ventricular tachycardia; EF < or = 40%), PVS was done (abnormal PVS: induction of monomorphic ventricular tachycardia, duration >10 s, cycle length > or = 230 ms). RESULTS Of 657 patients, 304 (46%) had either an abnormal HM or EF. The PVS performed in 146 of 304 patients was abnormal in 22. During a mean follow-up of 37 months, there were 106 (16%) deaths, being sudden in 24 (3.6%), nonsudden cardiac in 45 (6.8%). The incidence of arrhythmic events (sudden cardiac death, symptomatic ventricular tachycardia, cardiac arrest) was 18% (4/22) with an abnormal PVS and only 4% (5/124) with a normal PVS (odds ratio 4.0, p=0.032). CONCLUSIONS The rate of arrhythmic events is low in post-MI patients in the 1990s. Nevertheless, a two-step risk stratification is helpful in selecting candidates for a defibrillator trial aiming at primary prevention of sudden cardiac death after MI.

Estimation of enzymatic infarct size: Direct comparison of the marker enzymes creatine kinase and α-hydroxybutyrate dehydrogenase

BACKGROUND Estimation of infarct size with serum-time activity curves of creatine kinase (CK) (or CKMB) or alpha-hydroxybutyrate dehydrogenase (HBDH) is widely used in clinical trials. However, an independent variable such as left ventricular function has not been directly compared with CK and HBDH infarct size measurements in the same group of patients. METHODS AND RESULTS Infarct size was calculated by the CK area under the curve (AUC) and by the cumulative release of HBDH in 90 patients with acute myocardial infarction undergoing early thrombolysis. Infarct size estimates by CK AUC and HBDH release were closely correlated (r = 0.88, p < 0.0001). HBDH release was significantly better (p < 0.001) correlated to angiographically assessed ejection fraction 8 days after infarction (r = 0.74) than to CK AUC (r = 0.60), as was maximum HBDH (r = 0.71) compared with CK maximum (r = 0.59). In contrast to CK, maximum levels of HBDH only slightly overestimate myocardial damage in patients with early reperfusion. Data reanalyzed from the former placebo-controlled Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) study revealed significant differences in favor of streptokinase for CK and CKMB AUC and for HBDH maximum, but no difference for CK and CKMB maximums. CONCLUSIONS For comparative clinical trials HBDH appears to be the preferable marker enzyme for estimates of infarct size and measure of reperfusion effectiveness. In clinical practice one routine measure of HBDH serum activity on the second day after infarction may be a useful approximate value of infarct size.

Comparison of the diagnostic potential of four echocardiographic stress tests shortly after acute myocardial infarction: submaximal exercise, transesophageal atrial pacing, dipyridamole, and dobutamine-atropine

This study assessed and compared the diagnostic potential of submaximal exercise, transesophageal atrial pacing, dipyridamole, and dobutamine-atropine stress echocardiography tests shortly after acute myocardial infarction. In 121 study patients, 325 digital echocardiographic stress tests were attempted 10 to 11 days after acute myocardial infarction: 83 submaximal exercise tests, 121 high-dose dipyridamole echocardiography tests (DET), 69 transesophageal atrial pacing tests (< 150 beats/min), and 52 dobutamine tests, starting at 10 microgram/kg per minute, increasing stepwise to 40 microgram kg/min, and coadministering atropine in 12 patients (dobutamine-atropine stress echocardiography [DASE]). Results were correlated to a coronary artery diameter stenosis > or = 50% as determined by quantitative angiography. Feasibility to perform submaximal exercise echocardiography, atrial pacing echocardiography, DET, and DASE was 89%, 52%, 98%, and 88%, respectively. Atrial pacing was not tolerated by 18 patients and refused by 6 (9%). Severe but not life-threatening side effects were hypotension in DET (2%) and tachyarrhythmias in DASE (6%). Test positivity in multivessel disease with submaximal exercise, DET, and DASE was 55%, 93%, and 90%, respectively, and in 1-vessel disease 47%, 65%, 71%, and for atrial pacing, 82%, respectively. We conclude that submaximal exercise has limited sensitivity and atrial pacing limited feasibility. The pharmacologic stressors provide a useful, safe diagnostic approach: DET with slightly lower sensitivity in 1-vessel disease and DASE with insignificantly less feasibility.

Early assessment of outcome by ST-segment analysis after thrombolytic therapy in acute myocardial infarction

As an early marker of outcome, the sum of ST-segment elevation resolution between the electrocardiogram before and 3 hours after initiation of thrombolysis was investigated in 77 patients with acute myocardial infarction. Prospectively, three groups were defined according to complete (> or = 70%, n = 34), partial (< 70% to > or = 30%, n = 26), or no (< 30%, n = 17) ST resolution. There were considerable differences in the enzyme-determined infarct size (alpha-hydroxybutyrate dehydrogenase release for complete, partial, and no ST resolution: 529 +/- 397 IU/L, 689 +/- 484 IU/L, and 1293 +/- 742 IU/L, respectively; p = 0.0001) and the angiographic left ventricular function 1 week later (ejection fraction 58% +/- 10%, 53% +/- 13%, and 43% +/- 12%, respectively, p < 0.01; regional dyssynergic area 24 +/- 19, 39 +/- 23, and 50 +/- 21 U2, respectively, p < 0.01). Early reperfusion as assessed by creatine kinase release measured in 15-minute intervals was 90%, 65%, and 18%, respectively (p = 0.0001). Differences in degrees of ST-elevation resolution at 3 hours may help facilitate timely screening of patients for appropriate therapeutic intervention. Patients with complete ST resolution may be considered for early discharge, and patients with no ST resolution may be candidates for an early invasive approach or additional thrombolytic therapy.

Sudden increase of the ST segment elevation at time of reperfusion predicts extensive infarcts in patients with intravenous thrombolysis

Within 4 hours from the onset of symptoms in 61 patients with myocardial infarction and intravenous thrombolysis, ST segment elevation and creatine phosphokinase (CK) were measured every 15 minutes. Because of a premature enzyme rise, 42 patients (69%) were reperfused early (group 1). Immediately following reperfusion, eight of them (13%, group 1a) showed a marked increase of the ST elevation, in six of whom it was associated with clearly intensified chest pain. These patients exhibited a much steeper enzyme release and developed a larger enzymatic infarct size than patients (group 1b) without an additional transient ST elevation at reperfusion (CK peak 5.1 +/- 1.6 vs 9.8 +/- 4.2 hours after the start of thrombolysis; CK release 48 +/- 22 vs 19 +/- 18 IU/ml x hours, both p < 0.005). At angiography 11 days later, left ventricular function was significantly worse in group 1a than in group 1b (regional dyssynergic area 51 +/- 24 vs 21 +/- 18, global ejection fraction 39 +/- 14 vs 58 +/- 11; both p < 0.0005). During intravenous thrombolysis in acute myocardial infarction, some patients show a marked transient increase of the ST segment elevation at reperfusion. Their enzyme rise is very rapid and suggests a special reperfusion pattern. Most of these patients suffered large infarcts.

Implementation of evidence–based therapy in patients with systolic heart failure from 1998–2000

SummaryBackgroundIn recent years, the incidence of systolic heart failure has increased. Besides a complete revascularization, guideline–based medication represents the most effective therapeutic approach.AimAnalysis of adherence of guideline–recommended and actual medication during inpatient cardiac rehabilitation as well as under subsequent outpatient conditions.MethodsFrom 01/1998 to 12/ 2000, 1346 consecutive patients (64 ± 10 years, 73% male, LVEF 36.3 ± 8%, 88% ischemic, 6.7% valvular cardiomyopathy, 5.3% other causes, 11.8% atrial fibrillation) were included in a singlecenter prospective register. Medication was recorded at discharge and after the follow–up period of 731 ± 215 days. Trends in prescription rates were analyzed based on nonparametric correlations (Spearmans–Rho). Changes in medication from in– to outpatient settings were analyzed using exact McNemar test.ResultsAt discharge 75.3% (67.9%/68.9%/ 86.6% in 1998/1999/2000, p <0.001) of the patients were treated as recommended. This rate dropped to 68.3% at followup (p <0.0001). Mortality within the follow–up period was low (12.6%).ConclusionIt could be shown that from 1998 to 2000 inpatient guideline conformity was implementable adequately. Outpatient conformity was significantly lower. Although a high proportion of correctly prescribed CHF medication could be demonstrated, a further effort to improve guideline adherence in the management of heart failure patients is desirable.

Prognostische Bedeutung der ST-Strecken-Veränderung beim akuten Myokardinfarkt

The extent of ST segment elevation resolution (STR) 180 minutes after initiation of streptokinase treatment for acute myocardial infarction within 6 hours after onset of symptoms is an excellent early prognostic indicator that can be easily determined in all patients. This presentation is based on a meta-analysis from 3 thrombolysis studies including 3,912 patients. About 50% of patients had complete STR (> or = 70%). They had small enzymatic infarct sizes and well preserved left ventricular function associated with an excellent chance of survival. Patients with partial STR (< 70 to 30%) developed larger infarcts, but had still a relatively low mortality. To assess the optimal cut-off point that best predicts an increased mortality risk, the squared standardized log odds ratio statistics as a function of the hypothetical cut-off points in STR was used. A cut-off point around 30% STR was associated with an extraordinarily strong predictive power. The 35-day cardiac mortality with STR < 30% was 12.7% as compared to 2.1% for patients who had complete STR and 4.2% for those who had partial STR. Based on STR, age, medical history, and simple parameters at admission, a low risk population can be defined that includes about 50% of all patients aged < or = 70 years, and 20% of older patients. The 35-day and 1-year mortality rates for the group of younger patients was 1.4% and 2.7%, respectively, and for the older age group 5.0% and 7.9%. It appears highly unlikely that aggressive testing and interventions would have any measurable beneficial effect on such a good outcome. In thrombolytic therapy comparative trials STR may perform well as a surrogate endpoint, since it is more powerful than 90 minutes post-thrombolytic patency rates and early mortality, in a statistical sense. This is especially true for Phase-II dose-finding studies and the use as a surrogate or even primary endpoint in phase-III trials. In addition, STR may be very helpful for safety monitoring, interim analyses, and subgroup analyses in megatrials with the endpoint mortality. Use of STR can result in a substantial reduction in the required sample size. However, at least 1 pivotal mortality trial cannot be replaced by STR trials, since STR does not reflect the risk of intracranial hemorrhages and other bleeding complications.ZusammenfassungDas Ausmaß der Rückbildung der ST-Strecken-Hebung (STR) 180 Minuten nach Beginn einer Streptokinasebehandlung bei akutem Myokardinfarkt bis sechs Stunden nach Symptombeginn ist ein exzellenter prognostischer Frühindikator. In einer Metaanalyse von 3 912 Infarktpatienten wiesen etwa 50% eine komplette STR (STR≥70%) auf. Diese Patienten entwickeln kleine Infarkte und haben eine sehr hohe Überlebenswahrscheinlichkeit. Etwa 20% weisen keine STR (STR<30%) auf. Sie entwickeln große Infarkte und haben ein hohes Sterberisiko. Patienten mit partieller STR haben zwar größere Infarkte, aber die Überlebenschancen sind noch relativ gut.Mit Hilfe der STR ließ sich unter Berücksichtigung des Alters und der Anzahl weiterer bekannter Risikofaktoren aus Anamnese und Akutphase ein Niedrigrisikokollektiv mit einer so geringen Akut- und Ein-Jahres-Sterblichkeit ermitteln, daß zumindest für dieses Subkollektiv eine routinemäßige Koronarographie in der frühen Postinfarktphase nicht gerechtfertigt ist. Darüber hinaus ist STR geeignet, auch in Hochrisikokollektiven zwischen relativ stärker und weniger stark gefährdeten Patienten zu unterscheiden.In der Thrombolyseforschung ist STR hervorragend als Surrogatparameter einzusetzen. Insbesondere trifft das für Dosisfindungsstudien, als primärer Endpunkt in Phase-III-Studien und für Interimsanalysen, Subgruppenanalysen, Substudien und Sicherheitsanalysen in großen Mortalitäts-studien zu. STR kann erheblich zur Reduktion der erforderlichen Stichprobenumfänge in klinischen Studien beitragen. Allerdings ist zumindest eine große Mortalitätsstudie unerläßlich, um das Risiko von Hirnblutungen und anderen Blutungskomplikationen zu erfassen.AbstractThe extent of ST segment elevation resolution (STR) 180 minutes after initiation of streptokinase treatment for acute myocardial infarction within 6 hours after onset of symptoms is an excellent early prognostic indicator that can be easily determined in all patients. This presentation is based on a meta-analysis from 3 thrombolysis studies including 3 912 patients. About 50% of patients had complete STR (≥70%). They had small enzymatic infarct sizes and well preserved left ventricular function associated with an excellent chance of survival. Patients with partial STR (<70 to 30%) developed larger infarcts, but had still a relatively low mortality. To assess the optimal cut-off point that best predicts an increased mortality risk, the squared standardized log odds ratio statistics as a function of the hypothetical cut-off points in STR was used. A cut-off point around 30% STR was associated with an extraordinarily strong predictive power. The 35-day cardiac mortality with STR <30% was 12.7% as compared to 2.1% for patients who had complete STR and 4.2% for those who had partial STR.Based on STR, age, medical history, and simple parameters at admission, a low risk population can be defined that includes about 50% of all patients aged≤70 years, and 20% of older patients. The 35-day and 1-year mortality rates for the group of younger patients was 1.4% and 2.7%, respectively, and for the older age group 5.0% and 7.9%. It appears highly unlikely that aggressive testing and interventions would have any measurable beneficial effect on such a good outcome.In thrombolytic therapy comparative trials STR may perform well as a surrogate endpoint, since it is more powerful than 90 minutes post-thrombolytic patency rates and early mortality, in a statistical sense. This is especially true for Phase-II dosefinding studies and the use as a surrogate or even primary endpoint in phase-III trials. In addition, STR may be very helpful for safety monitoring, interim analyses, and subgroup analyses in megatrials with the endpoint mortality. Use of STR can result in a substantial reduction in the required sample size. However, at least 1 pivotal mortality trial cannot be replaced by STR trials, since STR does not reflect the risk of intracranial hemorrhages and other bleeding complications.