Albrecht Vogt

Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction : retrospective analysis of four German multicenter studies

OBJECTIVE This study evaluated the impact of early patency of the infarct-related vessel on short-term mortality after thrombolysis for acute myocardial infarction. BACKGROUND Different thrombolytic regimens for acute myocardial infarction proved to be equally effective in large scale mortality trials despite significant differences in their efficacy with respect to early infarct-related vessel patency as shown in smaller angiographic trials. METHODS Patients from four German multicenter studies of thrombolysis in acute myocardial infarction were retrospectively evaluated. Of 939 patients with acute myocardial infarction (duration of symptoms < 6 h) treated with thrombolysis, 907 (96.6%) had an angiogram of the infarct-related artery 90 min after the initiation of thrombolytic therapy. The perfusion status was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study criteria. RESULTS Complete reperfusion (TIMI grade 3) was found in 561 of 907 patients and partial reperfusion (TIMI grade 2) in 122 of 907. Overall, the in-hospital mortality rate was 4.6% (43 patients). In patients with complete reperfusion of the infarct-related vessel, the mortality rate was only 2.7% versus 7.1% in patients with an occluded vessel at the 90-min angiogram. This difference was highly significant in univariate as well as in multivariate analysis. In patients with partial perfusion of the infarct vessel, the mortality rate was 6.6%. CONCLUSIONS The early perfusion status of the infarct-related artery is an independent predictor of short-term survival. However, only complete early reperfusion is associated with a reduced in-hospital mortality rate whereas patients with partial perfusion (TIMI grade 2) have a short-term prognosis similar to that of patients with persistently occluded infarct vessels. Therefore, when used as a surrogate end point for mortality, only TIMI grade 3 perfusion of the infarct vessel should be interpreted as a treatment success of thrombolysis in acute myocardial infarction.

Randomized Comparison of Percutaneous Transluminal Coronary Angioplasty and Medical Therapy in Stable Survivors of Acute Myocardial Infarction With Single Vessel Disease A Study of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte

Background—Percutaneous transluminal coronary angioplasty of the infarct-related artery in stable survivors of acute myocardial infarction is often performed, even in patients without any symptoms or residual ischemia. Despite the lack of randomized studies, it is widely believed that this intervention will improve the clinical outcome of these patients. Methods and Results—Three hundred patients with single vessel disease of the infarct vessel and no or minor angina pectoris in the subacute phase (1 to 6 weeks) after an acute myocardial infarction were randomized to angioplasty (n=149) or medical therapy (n=151). Primary end point was the survival free of reinfarction, (re)intervention, coronary artery bypass surgery, or readmission for severe angina pectoris at 1 year. The event-free survival at 1 year was 82% in the medical group and 90% in the angioplasty group (P =0.06). This difference was mainly driven by the difference in the need for (re)interventions (20 versus 8, P =0.03). At long-term follow-up (mean, 56 months), survival was 89% and 96% (P =0.02). Survival free of reinfarction, (re)intervention, or coronary artery bypass surgery was 66% and 80% in the medically and interventionally treated patients, respectively (P =0.05). The use of nitrates was significantly lower in the angioplasty group, both at 1 year (38% versus 67%, P =0.001) and at long-term follow-up (36% versus 55%, P =0.006). Conclusions—Percutaneous revascularization of the infarct-related coronary artery in stable patients with single vessel disease improves clinical outcome at long-term follow-up and reduces the use of nitrates. The results of our study should be reproduced in a confirmatory study with a larger sample size before percutaneous coronary intervention in this low-risk patient subgroup, after myocardial infarction can be recommended as routine treatment in clinical practice.

Dose finding with a novel recombinant plasminogen activator (BM 06,022) in patients with acute myocardial infarction: Results of the German recombinant plasminogen activator study

OBJECTIVES The aim of this study was to determine the appropriate dose of a novel recombinant tissue-type plasminogen activator (BM 06.022) for thrombolysis in patients with acute myocardial infarction. BACKGROUND BM 06.022 is a mutant of tissue-type plasminogen activator expressed in Escherichia coli that can be given as a single bolus because of a prolonged half-life, which might obviate the need for complicated regimens. METHODS BM 06.022 given as a single bolus was investigated in 142 patients in a multicenter sequential dose-finding study. Efficacy of the drug was assessed from infarct-related artery patency by coronary angiography. RESULTS With the first dose of 10 MU of BM 06.022, the predefined minimal 90-min patency of 70% was not achieved, as indicated by the sequential probability ratio test after treatment of 42 patients (group A). The second dose of 15 MU of BM 06.022 was given subsequently in the preset maximum of 100 patients (group B). Angiography 30, 60 and 90 min after the bolus injection of BM 06.022 revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 65% and 66%, 73% and 74% and 66% and 75% of patients in groups A and B, respectively. Very early reocclusion up to the 90-min angiogram occurred in 17% and 13%, late reocclusion until predischarge angiography occurred in 7% and 5%, and rescue percutaneous transluminal coronary angioplasty after the 90-min angiogram was performed in 6 and 14 patients in groups A and B, respectively. Plasma fibrinogen decreased from 2.79 g/liter (range 0.94 to 4.75) to 1.69 g/liter (range 0.0 to 3.95) in group A and from 2.54 g/liter (range 0.0 to 5.02) to 0.92 g/liter (range 0.0 to 2.68) in group B. Two bleeding complications requiring transfusion or surgical intervention and one nonfatal intracranial hemorrhage were encountered. Eight patients had a reinfarction, and five patients died, all of cardiac causes. CONCLUSIONS With BM 06.022 given as a single bolus, a high early patency rate of the infarct-related coronary artery can be achieved. The speed of thrombolysis seems to be superior to standard thrombolytic drugs. The compound warrants further evaluation with respect to safety and efficacy by clinical end points.

Open, noncontrolled dose-finding study with a novel recombinant plasminogen activator (BM 06.022) given as a double bolus in patients with acute myocardial infarction.

The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mutant of tissue-type plasminogen activator expressed in escherichia coli which can be given as a bolus because of a prolonged half-life. The primary objective of this trial was to determine the efficacy of an intravenous r-PA double bolus (first bolus of 10 MU followed by 5 MU after 30 minutes) in patients with acute myocardial infarction. All patients received heparin intravenously and acetylsalicylic acid orally. Efficacy was assessed from infarct artery patency by coronary angiography (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3) in 50 patients. Ninety minutes after administration of the first r-PA bolus, the infarct-related coronary artery was patent in 39 of 50 patients (78%; 95% confidence interval 64 to 88%). An angiographically confirmed reocclusion occurred in 1 patient between 90 minutes and 24 to 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic parameters showed a decrease in fibrinogen to 37% of baseline value. There were 3 clinical reinfarctions before discharge and 2 major puncture site hemorrhages. No further serious bleeding and no serious adverse event with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regimen appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limited number of patients treated in this study, one need not be concerned about the safety profile of r-PA.

Incidence, management, and outcome of stent loss during intracoronary stenting.

C stent embolization is an uncommon but potentially hazardous complication of percutaneous transluminal coronary angioplasty (PTCA). Previous small-sized clinical studies reported incidence rates ranging from 0.9% to 8.4%.1–5 In this study we report the incidence, management, and hospital follow-up of a large, consecutive series of patients with coronary stent embolization. • • • The German registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte includes prospectively all PTCA procedures from 74 centers since October 1992. The organization of the registry has been published elsewhere.6 Two audit visits per year ensured the completeness of the data including complications. From August 23, 1995, to June 28, 1997, a total of 56,807 PTCA procedures were registered. In 20,298 patients,

Acute effects of the new angiotensin converting enzyme inhibitor ramipril on hemodynamics and carotid sinus baroreflex activity in congestive heart failure.

1 stents were implanted (implantation rate 35.7%). A total of 25,558 stent implantations resulted in 1.26 stents per procedure. Four hundred twenty-nine lost stents were documented and were analyzed retrospectively by a detailed questionnaire. The clinical follow-up on 18 patients was incomplete or not available. Thus, the study presents data of 411 stent embolizations in 387 patients involving 96% of all stents lost (Table 1). During the same time interval, similar data from 19,869 consecutive patients having undergone stent procedures without embolization were collected; these patients served as a control population to the lost stent cohort. The outcomes of interest were all-cause mortality, nonfatal acute myocardial infarction (AMI), the need for coronary artery bypass graft (CABG) surgery, and noncoronary sequelae after stent embolization. Continuous variables are expressed as mean 6 1 SD. The likelihood ratio test as chi-square test was used to test homogeneity; the significance was calculated by Fisher’s exact test. A 2-tailed p value ,0.05 was considered significant. Baseline characteristics of patients who had stent embolization are detailed in Table 1. On the basis of 25,558 implanted stents and 20,298 treated patients the incidence of stent loss amounted to 1.7% per implanted stent and 2.1% per treated patient. Patients with stent loss were older than patients without stent loss (64.4 6 9.2 vs 60.7 6 9.7 years; p ,0.001). Angiographic characteristics, target lesions, and technical approach are listed in Table 2. A multiple group comparison identified 3 groups of target lesions: stent embolization in the left anterior descending coronary artery was underrepresented, whereas embolization in the left main coronary artery was overrepresented. Stents placed in the left circumflex artery, right coronary artery, and bypass graft showed average rates of embolization (p ,0.0001). The number and type of lost stents are detailed in Table 3. For statistical purposes only, stent types with .1,000 implantations were considered. The 4 major stent types, Palmaz-Schatz, Micro-stent, MultiLink, and Wiktor (68.1% of implantations) were composed of 6.9% of lost stents. However, 3 groups of stent embolization rates could be distinguished. Manually crimped Palmaz-Schatz and Wiktor stent embolized most often, whereas the MultiLink stent embolized least. The Micro, Pura, Nir, and Sitomed stent showed average rates of stent embolization (p ,0.001). The causes of stent loss, their location, and management are presented in Table 4. The operator tried to retrieve the embolized stent in 63% of cases. However, only 118 stents (29%) could be retrieved. In 36 cases (9%) the guiding catheter sprung uncontrollably into the aortic root during catheter manipulations pulling the stent-balloon assembly together with the guidewire outside the coronary artery. In 4 cases an inserted stent was displaced when it was crossed by a second stent. In another 4 cases a second stent embolized while crossing an already deployed stent. Only 1 embolization was due to balloon rupture. The stent was lost within the coronary arteries in 45% of cases and outside the coronary arteries in the remainder. Eighty-two embolized stents were successfully implanted or fixed in a site initially not selected From the General Hospital Hamburg-Altona; Klinikum Ingolstadt; Klinikum Kassel; Zentral-Krankenhaus Links der Weser Bremen; and Stadtische Kliniken Karlsruhe, Hamburg, Germany. Dr. von Olshausen’s address is: 3rd Medical Department, Cardiology, General Hospital Hamburg-Altona, Paul-Ehrlich-Strasse 1, D-22763 Hamburg, Germany. E-mail: klausvo@t-online.de. Manuscript received November 24, 2000; revised manuscript received and accepted April 11, 2001. TABLE 1 Characteristics of 387 Patients With Stent Loss

Frequency of achieving optimal reperfusion with thrombolysis in acute myocardial infarction (analysis of four German multicenter studies)

The hemodynamic effects of a single dose of 5 mg of ramipril, a new angiotensin converting enzyme inhibitor, were investigated in 10 patients with chronic congestive heart failure. Arterial blood pressure and total peripheral resistance were decreased by approximately 12% without causing reflex tachycardia. A highly significant decrease occurred in mean pulmonary artery and pulmonary capillary wedge pressures. These hemodynamic changes were equally pronounced at rest and during exercise on a bicycle ergometer; the effect was of the same magnitude 5 and 24 hours after medication. Angiotensin converting enzyme activity in plasma was nearly completely inhibited after 5 hours and remained at about 12% of control after 24 hours. Cardiac index, which was normal before treatment, remained unaffected. Thus, ramipril induced a balanced reduction of left ventricular pre- and afterload. The activity of the carotid sinus baroreflex was investigated in 8 of the patients using the neck suction technique before and 24 hours after ramipril. The reflex bradycardia during stimulation of the baroreceptors was significantly increased by ramipril, whereas the decrease in blood pressure remained essentially unaffected. Ramipril induced a selective sensitization of the parasympathetic baroreceptor heart rate reflex without influencing the sympathetically mediated peripheral vasodilatation. This effect may be responsible for the lack of reflex tachycardia in spite of the decrease in blood pressure.

Frequency of “optimal anticoagulation” for acute myocardial infarction after thrombolysis with front-loaded recombinant tissue-type plasminogen activator and conjunctive therapy with recombinant hirudin (HBW O23)☆

Patients from 4 German multicenter studies on thrombolysis in acute myocardial infarction (AMI) were retrospectively evaluated to assess the incidence of optimal reperfusion, defined as a completely perfused infarct vessel after 90 minutes, without subsequent death or reinfarction, and without reocclusion or deterioration of flow in control angiograms. Of 907 patients with a 90-minute angiogram, 75% had an open infarct vessel by conventional definition (perfusion grade 2 or 3 according to the criteria of the Thrombolysis in Myocardial Infarction [TIMI] study). However, only 62% had TIMI grade 3 complete perfusion. Of the 561 patients with such primary treatment success, 106 (19%) had secondary treatment failure by death, reinfarction, or subtotal or total reocclusion of the infarct vessel. In a subset of 668 patients with a first angiogram after 60 minutes, conventional patency was 70%, complete perfusion 51%, and an optimal perfusion result was achieved in only 42%. The efficacy of thrombolysis in AMI is substantially overestimated by conventional 90-minute patency rates.

Therapie des akuten Myokardinfarkts — Primäre PTCA oder Thrombolyse?

Abstract This retrospective analysis reviewed 183 patients with acute myocardial infarction who were given front-loaded recombinant tissue-type plasminogen activator (rt-PA) and r-hirudin (HBW 023) in 1 of 4 dose groups (bolus dose of 0.07, 0.1, 0.2, or 0.4 mg/kg, followed by an infusion of 0.05, 0.06, 0.1, or 0.15 ma/kg/hour over 48 hours). Activated partial thromboplastin time (aPTT) levels were determined at baseline and at 4, 8, 12, 16, 20, 24, 32, 40, and 48 hours. Of the 178 patients with r-hirudin treatment for ≥12 hours, anti-coagulation was optimal in 55.1% (all aPTTs >2 × baseline), suboptimal in 33.7% (lowest aPTT >1.5 but

Does digoxin sensitize left ventricular mechanoreceptors

ZusammenfassungDie Thrombolyse ist etablierte Standardbehandlung zur Reperfusion des Infarktgefäßes. Die direkte PTCA ist eine Alternative, die zu vergleichbaren klinischen Ergebnissen führt, wenn sie ohne Verzögerung vor Ort durch ein erhahrenes Team durchgeführt werden kann. Beim ansonsten unkomplizierten Infarkt ist das klinische Ergebnis der direkten PTCA nicht entscheidend besser als das der Thrombolyse trotz höherer Erfolgsraten bezüglich der Reperfusion. Die PTCA ist vorzuziehen bei Kontraindikationen gegen Thrombolyse, bei unsicherer Infarktdiagnose und möglicherweise bei hämodynamisch schwer kompromittierten Patienten. Im kardiogenen Schock wird aufgrund eines allgemeinen Konsenses die PTCA für wirksamer gehalten als die Thrombolyse. Dieser Konsens wird jedoch nicht durch zuverlässige klinische Untersuchungen gestützt. Verbesserungen der klinischen PTCA-Ergebnisse über das bisher in vergleichenden Studien erreichte Niveau sind möglicherweise durch Stentimplantation und durch moderne Plättchenhemmer (GPIIb/IIIa-Antagonisten) zu erwarten, dies ist jedoch bisher nicht sicher belegt.AbstractSince reperfusion of the infarct-related coronary artery has been established as a mainstay in the treatment of acute myocardial infarction (AMI) mechanical recanalization by direct angioplasty has been used as an alternative to the standard treatment with thrombolysis. Direct PTCA is more efficient than thrombolysis in terms of reperfusion rates, whereas thrombolysis is more readily available. Thrombolysis reduces mortality from AMI by approximately 25%. The clinical efficacy is strongly time-dependent, and treatment within the first hour of AMI improves survival by nearly 50% by preventing transmural infarction in a significant proportion of the patients. The disadvantage of thrombolysis is its limited efficacy in terms of rapid, complete and sustained patency of the infarct vessel yielding optimal results in only 50% of the patients. Direct PTCA is generally agreed to be more efficient to recanalize the infarct vessel, but its clinical advantage remains controversial. The first randomized studies of direct PTCA in AMI from highly specialized centers in selected patients reported success rates of coronary reperfusion up to 97% resulting in a trend to less death and reinfarction; but the differences were significant only in a meta-analysis of these small studies. The real world of direct PTCA has been depicted by a large registry in Germany of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK) now including more than 4,000 direct PTCA-procedures since 1994. In this registry, the success rate of direct PTCA was 87% as defined by a final TIMI-grade 3 perfusion of the infarct vessel which is close to the data of the MITI-registry and the GUSTO IIb study. Failed PTCA was associated with an exceptionally high mortality rate of 36% confirming earlier observational reports. The non-randomized comparison of thrombolysis and direct PTCA in the MITI-registry showed no difference in survival or reinfarction rates, and the randomized GUSTO IIb substudy of direct PTCA versus front-loaded alteplase showed a small advantage in death and reinfarction rates at 30 days which dissipated over time leaving no significant clinical advantage of direct PTCA over thrombolysis at 6 months. Thus, in myocardial infarction in general the advantage of direct PTCA over thrombolysis is at best minimal. The reason is very probably the longer time lag until the procedure is started, the lower success rate as compared to the first reports of some specialized centers, and the clearly negative impact of failed PTCA on survival. Moreover, the immediate success of direct PTCA seems to be overestimated by the operator as demonstrated by comparison of central and local estimates of the TIMI flow rates in GUSTO IIb.Improvements of direct PTCA in AMI might be possible by coronary stenting which has markedly increased to more than 60% during the last year in the ALKK-registry. This was accompanied by a slight decrease in death and reinfarction rates. Further improvements can be expected from GP IIb/IIIa platelet antagonists which are under clinical investigation.It has been claimed, that in cardiogenic shock direct PTCA is more effective than thrombolysis. This hypothesis is based on comparison of failed versus successful PTCA-attempts, but this comparison is not valid since failed procedures clearly increase mortality. In the GUSTO-I study patients with cardiogenic shock had lower mortality with than without an early coronary angiogram. This survival advantage, however, was independent of revascularization since only half of the patients with an early angiogram had PTCA. The same was observed in the International Shock Registry, reflecting significant selection bias in that patients in relatively better condition will be taken to the cathlab whereas apparently hopeless cases will not. In the ALKK-registry half of the patients in cardiogenic shock died after direct PTCA casting doubt on the presumed high clinical efficacy of this strategy. A definitive answer to the role of PTCA in cardiogenic shock could only be given by randomized studies, but these have been stopped prematurely for poor patient recruitment. Thus, the consensus to prefer PTCA over thrombolysis in cardiogenic shock is not based on firm clinical data.