Thomas Linderer

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.

Increased morning incidence of myocardial infarction in the ISAM Study: absence with prior beta-adrenergic blockade. ISAM Study Group.

The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves. The incidence of myocardial infarction was markedly increased between 6:00 AM and 12:00 noon compared with other times of day (p less than 0.001). Myocardial infarction occurred 3.8 times more frequently between 8:00 and 9:00 AM (hour of maximum incidence) than between 12:00 midnight and 1:00 AM (hour of minimum incidence). Time of myocardial infarction based on clinical and enzymatic methods correlated well (r = 0.95). Patients with higher or lower left ventricular ejection fraction, higher or lower degree of wall motion abnormalities and residual stenosis of the coronary arteries, and one-, two-, or three-vessel disease exhibited a similar circadian pattern, suggesting that the morning is a risk period for patients with mild as well as severe coronary artery disease. Only the group of patients receiving beta-adrenergic blocking therapy before the event did not show an increased morning incidence of myocardial infarction. This observation may contribute to an understanding of the mechanisms by which beta-blockers reduce the incidence of myocardial infarction. Further investigation of physiologic changes occurring during the morning period of increased risk of myocardial infarction may lead to better understanding of the disorder. Design and timing of cardioprotective medication may play a crucial role in improving prevention of acute myocardial infarction.

Intravenous short-term infusion of streptokinase in acute myocardial infarction.

Short-term i.v. infusion of streptokinase was performed in 93 patients within 6 hours after the onset of acute myocardial infarction. Twenty-six patients underwent angiography in the acute phase (group A) and 52 underwent angiography in the fourth week only (group B); 15 patients had no angiography. Seven patients died during the hospital stay and six suffered nonfatal reinfarctions. There were no bleeding complications. In 11 of 21 group A patients, occluded coronary arteries were opened within 1 hour after the streptokinase infusion was started. In 84% of groups A and B, the infarct-related coronary artery was patent in the fourth week. In 75% of the patent arteries, the residual luminal diameter stenosis was less than 70%. According to serial serum CK-MB curves, recanalization was achieved mostly within 1–2 hours. Myocardial salvage was indicated by improvement in local contraction disorders in the recanalized group A patients and by the significant relationship between infarct size and time from symptom onset to treatment in group B. These data suggest that a high-dose, short-term, i.v. infusion of streptokinase is a safe and efficient method of restoring coronary blood flow. Expeditious initiation of i.v. streptokinase infusion is a critical determinant for early recanalization and salvage of myocardium. Patients with thrombotically subtotal occlusion probably receive the most benefit. Evaluation of the true impact on survival and myocardial function will require controlled clinical trials.

A prospective placebo-controlled double-blind multicenter trial of intravenous streptokinase in acute myocardial infarction (ISAM): Long-term mortality and morbidity

Long-term mortality and morbidity of 1,741 patients with acute myocardial infarction, treated with intravenous streptokinase (1.5 million IU/h) or placebo, was assessed in a double-blind placebo-controlled trial (ISAM). At the 7 month follow-up, 94 (10.9%) of the 859 patients in the streptokinase group and 98 (11.1%) of the 882 patients in the placebo group had died; at an average follow-up of 21 months, 14.4% of the streptokinase group and 16.1% of the placebo group had died. The differences were not statistically significant. Long-term mortality was slightly higher in patients with anterior myocardial infarction and streptokinase treatment (20.1 versus 18.4%) and lower in patients with inferior myocardial infarction (10.2 versus 14.2%). Patients with previous myocardial infarction had a higher long-term mortality rate with streptokinase (34.9 versus 21.5% with placebo, p = 0.03). At 7 months, there were significantly more cases of reinfarction in the streptokinase group (7.2 versus 4.5%, p = 0.02). It is concluded that despite a significant limitation of infarct size by intravenous streptokinase, long-term mortality is only slightly reduced and reinfarction is significantly more frequent. Both findings suggest the need for complementary therapy such as revascularization procedures after thrombolysis.

Prehospital thrombolysis: Beneficial effects of very early treatment on infarct size and left ventricular function

OBJECTIVES The purpose of this study was to compare the effects of very early (< or = 1.5 h after symptom onset) and later (> 1.5 up to 4 h) thrombolytic therapy on infarct size, left ventricular function and early mortality in patients with acute myocardial infarction. To start thrombolysis at the earliest possible moment, it was performed in the prehospital setting. A cutoff time of 1.5 h was prospectively stipulated. BACKGROUND Shortening of ischemic time is crucial within the 1st 2 h. Prehospital thrombolysis can reduce time to treatment and enables very early initiation of therapy for many patients. METHODS One hundred seventy patients received 30 mg of anistreplase up to 4 h from symptom onset by a mobile intensive care unit physician. Infarct size was measured from cumulative release of alpha-hydroxybutyrate dehydrogenase, and left ventricular function was assessed by contrast angiograms 10 days after the infarction. RESULTS The decision to treat on scene was correct in 98% of patients. There were no bleeding complications or deaths outside the hospital setting. In 28 patients (17%) the ischemic process was interrupted. Findings with thrombolytic therapy initiated < or = 1.5 (96 patients) versus > 1.5 h (74 patients) were the following: initial extent of epicardial injury, 1.6 +/- 0.9 versus 1.4 +/- 0.7 mV, p = NS; infarct size by cardiac enzyme release 646 +/- 634 versus 886 +/- 712 IU/liter, p < 0.05; ejection fraction 57 +/- 14% versus 51 +/- 13%, p < 0.05; regional dyssynergic area 24 +/- 22 versus 33 +/- 24 U, p < 0.05; 21-day mortality 1 of 96 versus 5 of 74 patients (1% vs. 7%, p < 0.05). CONCLUSIONS The data suggest that in evolving myocardial infarction up to 4 h in duration, the start of thrombolytic therapy at < or = 1.5 h compared with > 1.5 h limits infarct size, preserves left ventricular function and may save lives.

Follow-up after coronary arterial reperfusion with intravenous streptokinase in relation to residual myocardial infarct artery narrowings

Short- and long-term changes in residual stenosis of the myocardial infarct-related coronary arteries in patients with successful reperfusion by intravenous streptokinase have not been determined until now. In 15 patients the residual diameter stenosis decreased significantly from 62 +/- 9% after 24 hours to 55 +/- 13% in the fourth week (p less than 0.005). Quantitative angiographic analyses in 61 patients with patent infarct-related coronary arteries in the fourth week revealed a mean diameter stenosis of 61 +/- 13%. The patients were followed up 34 +/- 10 months. Sixteen had elective coronary artery bypass surgery or percutaneous transluminal coronary angioplasty (PTCA). Eighteen without coronary artery bypass surgery or PTCA had undergone repeat angiography after 26 +/- 9 months. Twenty-five (41%) have had a residual diameter stenosis greater than 65% in the fourth week. A stenosis greater than 65% was found in: 4 of 5 patients with late reinfarction; 3 of 7 with 1-vessel coronary artery disease and persistent angina, compared with none of 11 with a stenosis less than 65%; 6 of 7, whose silent reocclusion had been found at long-term follow-up compared with 1 of 9 with a residual stenosis less than 65%. In 8 patients with persistent patency of the infarct artery, the stenosis had decreased significantly from 55 +/- 6% to 36 +/- 12% (p less than 0.005). Correspondingly, there was a significant improvement in the infarct-related left ventricular wall motion disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative in-vitro validation of eight first- and second-generation quantitative coronary angiography systems

BackgroundIt is known that first-generation quantitative coronary angiography (QCA) systems overestimate small vessel sizes owing to the point-spread function of the respective X-ray imaging chain. With second-generation systems new algorithms were introduced to correct for this source of error. ObjectiveTo evaluate the efficiency of the modified contour detection algorithms. MethodsSix second-generation QCA systems (CMS, QANSAD, AWOS, CAAS II, Cardio 500, and Angioimage) were validated and compared with first-generation systems (CAAS and ARTREK). By using an arterial phantom consisting of stenotic and nonstenotic glass tubes (of diameters 0.5–5.0 mm) the accuracy and precision of each analysis system, as well as their additional accuracy and precision values for phantom diameters ≤ 1.0 mm were determined. ResultsAll systems had high accuracy and precision values, but first-generation systems overestimated small vessel diameters. With second-generation systems a significantly improved accuracy in the submillimeter range (an accuracy within ± 0.028 mm) was obtained. This improvement was accompanied by a moderate reduction in precision in the submillimeter range. ConclusionThe new algorithms of the second-generation QCA systems allow accurate and reliable measurements of small coronary dimensions and, therefore, precise analysis of coronary stenoses of moderate-to-high grade seems feasible with the improved accuracy of the new systems.

Impact of late coronary artery reperfusion on left ventricular function one month after acute myocardial infarction (results from the ISAM study)

To evaluate the impact of late reperfusion of an infarct-related coronary artery on left ventricular (LV) function in the month after myocardial infarction, findings from 368 patients in the Intravenous Streptokinase in Myocardial Infarction study are presented. All patients had a late peaking in the creatine kinase-MB serum time-activity curve, suggesting absence of early reperfusion. Contrast angiography was performed 1 month after the acute event. The infarct-related coronary artery was patent in 74 of 116 (64%) streptokinase-treated patients and 141 of 252 (56%) patients treated with anticoagulant therapy (placebo group). In all baseline variables, including the actually developed enzymatic and electrocardiographic infarct sizes, there were no differences between the patent- or occluded-artery groups. A patent infarct artery 1 month after infarction was associated with significantly better LV function regardless of the vessel involved and whether or not patients had been treated with streptokinase. Ejection fraction in patients with patent versus occluded artery was 56 +/- 13 versus 50 +/- 14 (p less than 0.0005). Most benefit was noted in patients in whom the proximal left anterior descending coronary artery was affected: ejection fraction was 52 +/- 14 versus 36 +/- 12% (p less than 0.0005). Our data confirm that restoration of adequate flow through an infarct-related coronary artery beyond the time window for actual salvage of ischemic myocardium has a definite beneficial effect on LV function.

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.