Left atrial thrombi and spontaneous echo contrast in patients with atrial fibrillation : Systematic analysis of a single-center experience.

BACKGROUND: Atrial fibrillation is associated with a high risk for thromboembolic events. Thrombi in the left atrial appendage and spontaneous echo contrast (SEC) correlate positively with this embolic risk. We studied the laboratory, echocardiographic, and epidemiologic parameters that could predict left atrial thrombi and the intensity of the SEC. PATIENTS AND METHODS: Between September 2013 and June 2015 we included 372 patients with atrial fibrillation before planned electrical cardioversion (transesophageal-guided strategy) in this study. After assessing the risk of stroke and bleeding (CHA2DS2-VASc and HAS-BLED scores), we measured the concentration of the D-dimer and B-type natriuretic peptide at the time of the transesophageal echocardiography as well as the left atrial volume and the ejection fraction during transthoracic echocardiography. RESULTS: The ejection fraction and the CHA2DS2-VASc score were identified as independent predictors of both left atrial thrombi and SEC, whereas the left atrial volume could only predict the intensity of SEC. In contrast to the results of other studies, the biomarkers in this study failed to predict the outcome. CONCLUSION: Only the echocardiographic and epidemiologic parameters were predictors of left atrial thrombi and SEC intensity, while the studied biomarkers had no predictive power. Using clinical data and transthoracic echocardiography, we can change the therapeutic strategy in high-risk patients.

[Acute hepatic failure after ingestion of mushrooms]. / Akutes Leberversagen nach Pilzingestion.

This report is about a married couple who were admitted to hospital suffering from gastrointestinal complaints after eating mushrooms. With the suspicion of poisoning with Amanita phalloides treatment started with elimination of the toxins, symptomatic therapy and specific therapy with silibinin. After quantitative determination of the Amanita toxins the patients were immediately transferred to a university hospital.Poisoning by the death cap mushroom is responsible for acute hepatic and often also renal failure and is accompanied by a high mortality. Clinical symptoms follow a three-phase course with gastrointestinal complaints, an asymptomatic interval and finally the hepatorenal phase. Even in suspected cases of intoxication, treatment should be started by antidote therapy with silibinin.

Leisure sport activity as a trigger for acute coronary events in men without known coronary artery disease : a single-center case study.

INTRODUCTION: Leisure sport activity (LSA) is gaining in importance among middle-aged and senior men in the German population. There is a consensus that regular aerobic exercise at moderate intensities and increased physical fitness are associated with a reduced risk of fatal and nonfatal acute cardiac events (ACE) in middle-aged individuals. However, vigorous exercise (VE) can acutely and transiently increase the risk of an ACE in susceptible individuals. There is an ongoing discussion as to whether preparticipation screening may prevent such events. This case study characterizes patients participating in LSA who had not been involved in preparticipation screening prior to their ACE. METHODS: In the period between June 2003 and July 2009, all consecutive patients with an ACE presenting at the catheter laboratory were retrospectively screened for VE that had occurred during LSA. All 13 men with previously unknown coronary artery disease (CAD) had exercised regularly. All patients underwent coronary angiography. This study characterized clinical parameters, duration of LSA, coronary diagnostic procedure, as well as therapeutic intervention. RESULTS: In seven patients, cardiovascular (CV) risk factors comprised arterial hypertension in seven, hyperlipidemia in seven, smoking or former smoking in two, family history of CV disease in four, and previous peripheral atherosclerotic disease in two. The culprit lesion was identified in seven patients in the left anterior descending artery, in four in the right coronary artery, and in two in the circumflex artery. The mean left ventricular ejection fraction was 65% (45-84). The mean complexity of the lesions using the syntax score was 17 (2-36). PCI was performed in 12 patients, while one patient was transferred for coronary artery bypass grafts. All patients survived their ACE. CONCLUSION: This case study supports the data indicating that ACE in men with previously unknown CAD is not uncommon during LSA. This patient cohort provides data on a group of patients who might benefit from preparticipation screening.

The management of chronic total coronary occlusions.

Although recent consensus has clearly defined chronic total occlusions (CTO), attempted percutaneous coronary intervention (PCI) remains low. Histopathologically, CTOs are characterized by fibrous caps, varying degrees of plaques, and neovascularization, with both increasing with the age of the CTO. Multiple registries and studies show that successful PCI of CTOs can improve symptoms, left ventricular function, and mortality. There is overwhelming evidence that very low restenosis and reocclusion rates can be obtained with drug eluting stents after recanalization of CTOs. PCI should be considered the preferred initial revascularization modality in patients in whom a high procedural success rate may be anticipated. Novel techniques have greatly enhanced procedural success, and include ''parallel'' and ''seesaw'' wire techniques, balloon anchoring, subintimal tracking and reentry (STAR), retrograde approach, contralateral injection, and intravascular ultrasound (IVUS) guidance. Improvements in wire technology have largely been responsible for improved procedural success in PCI of CTO, while application of new technologies hold promise to significantly better outcomes. Magnetic resonance imaging (MRI) and multislice computed tomography (CT) are already employed in formulating treatment strategies and their role in the treatment of CTOs is likely to increase.

[Acute pulmonary embolism: still a diagnostic and therapeutic challenge?] / Akute Lungenembolie: immer noch eine diagnostische und therapeutische Herausforderung?

BACKGROUND: Acute pulmonary embolism (PE) is a cardiovascular emergency with high mortality in which a rapid diagnosis and the early initiation of therapy is vital. In the present study patients with acute PE hospitalized at the Clinic Lippe in Detmold were characterized and their prognosis examined. METHODS: In our department at the hospital Detmold, all patients with acute PE admitted in 2012 and 2013 were documented with respect to the severity of PE, predisposing risk factors and diagnostic and therapeutic steps. RESULTS: A total of 170 patients with acute PE were documented of which 80 patients (47 %) had low, 70 patients an intermediate (41 %) and 20 a high risk (12 %). The main diagnostic tool was thoracic computed tomography (82 %). All patients initially received unfractionated or low-molecular weight heparin; systemic intravenous fibrinolysis was carried out in 3 % of patients (intermediate risk n = 1, high risk n = 4). Nineteen percent (n = 13) of the patients at intermediate and 30 % (n = 6) of patients at high risk received local intrapulmonary fibrinolysis. Overall, the mortality rate in hospital was 10 % (low risk 2.5 %; intermediate risk 7 %; high risk 58 %). All 5 patients who received systemic emergency lysis died. One (5.3 %) of the 19 patients at intermediate risk, undergoing local intrapulmonary fibrinolysis, died. CONCLUSION: In acute PE a rapid diagnosis and the initiation of an adequate therapy remains a big challenge. Further studies are required to evaluate if aggressive treatment options might reduce mortality especially among patients at intermediate or high risk.

Papillary fibroelastoma of the ascending aorta presenting with cardiogenic shock.

We describe an uncommon case of a 58-year-old woman who presented with cardiogenic shock. The echocardiography examination revealed a papillary fibroadenoma located in the ascending aorta which was subsequently surgically treated.

[Treatment of coronary three-vessel disease in patients above 75 years]. / Therapie der koronaren Dreigefäßerkrankung bei Patienten über 75 Jahren.

BACKGROUND: Chronic ischemic heart disease take the first place in cause of death in Germany. The proportion of patients aged 75 years or older amounts more than 80 %. Due to their growing part of population the medical care of older patients becomes increasingly important. In this investigation patients aged ≥ 75 years with coronary three-vessel disease were characterized and various treatment strategies were compared. PATIENTS AND METHODS: This analysis was retrospective. The data of patients aged 75 years or older with three-vessel disease diagnosed by coronary angiography at the Klinikum Lippe Detmold between 2005 and 2007 were collected. Depending on the received therapy they were parted in three groups: optimal drug therapy (OMT), interventional - (PCI) and surgical revascularization (CABG). Patient characteristics as well as survival- and MACCE-rates during follow up were ascertained. Subgroup analyzes were performed for acute coronary syndrom (ACS) and stable coronary artery disease( CAD). RESULTS: The data of 434 patients with an average age of 79 years were documented. 139 (32.0 %) were assigned to the OMT- 189 (43.6 %) to the PCI- and 106 (24.4 %) to the CABG-group. Overall there was no significant difference between the three groups regarding mortality. In the subgroup of patients wit ACS (n = 180) mortality significantly increased in the OMT-group compared to the two invasive therapies (PCI (p = 0.029), CABG (p = 0.045)). The subgroup of patients with stable CAD showed no significant differences in mortality between the three types of therapy. CONCLUSIONS: Older patients benefit from an interventional or surgical revascularization in the context of ACS. In contrast, in elderly with stable CAD optimal medical therapy provides a reasonable alternative to invasive therapy without increase in mortality.

Improvement of global and regional left ventricular function by percutaneous transluminal coronary angioplasty after myocardial infarction.

OBJECTIVES: This study was designed to evaluate how elective percutaneous transluminal coronary angioplasty of the infarct-related vessel after acute myocardial infarction affects global ejection fraction and regional wall function. BACKGROUND: The severity of the residual stenosis of the infarct-related artery after thrombolysis is an important predictor of changes in left ventricular function; however, the optimal time to restore complete perfusion in the infarct area has not been determined. METHODS: We prospectively evaluated patients with a first myocardial infarction, postinfarction ischemia and residual high grade stenosis with reduced flow in the infarct-related artery who underwent successful coronary angioplasty. The group comprised 74 patients (61 men, 13 women with a mean age +/- SD of 55.9 +/- 9.9 years). Global ejection fraction and infarct region function (expressed as area ejection fraction) were angiographically measured before coronary angioplasty (3.9 +/- 2.1 weeks after infarction) and on routine follow-up study 6 +/- 1 months after angioplasty. RESULTS: Restenosis with reduced flow occurred in 15 patients (20%). The global ejection fraction in patients with complete flow at follow-up increased significantly from 56.8% +/- 12% to 62.3% +/- 12.5% (p < 0.001). Regional wall motion of the infarct area increased from 12.1% to 22.5% (p = 0.001) in patients with anterior wall infarction and from 20.4% to 28.5% (p = 0.002) in those with inferior wall infarction. In patients with restenosis there was no difference at follow-up either in global ejection fraction (from 47.7% +/- 7.7% to 47.1% +/- 12.7%, p = 0.57) or in regional wall motion of the infarct area. CONCLUSIONS: Global and regional myocardial dysfunction due to postinfarction ischemia lessens significantly after successful coronary angioplasty of the infarct-related coronary artery with long-term sustained normal, complete flow. In contrast, restenosis with reduced flow prevents long-term improvement of left ventricular function.

Intravenous streptokinase in acute myocardial infarction (I.S.A.M.) trial: serial evaluation of left ventricular function up to 3 years after infarction estimated by radionuclide ventriculography. I.S.A.M. Study Group.

The Intravenous Streptokinase in Acute Myocardial Infarction (I.S.A.M.) trial was a prospective, placebo-controlled, double-blind multicenter trial of high-dose short-term intravenous streptokinase in acute myocardial infarction administered within 6 h after the onset of symptoms. Global and regional left ventricular ejection fractions were determined by radionuclide ventriculography in a subset of 120 patients 3 days, 4 weeks, 7 months, 18 months and 3 years after acute myocardial infarction. In patients with anterior myocardial infarction, left ventricular ejection fraction was higher in the streptokinase than in the placebo group 3 days after acute infarction (49 +/- 14% vs. 40 +/- 11%, p = 0.02). This difference of about 10% units in ejection fraction persisted during the 3 year follow-up period. Among streptokinase-treated patients, regional left ventricular ejection fraction was higher within the infarct zone as well as in remote myocardium throughout the follow-up period. Among patients with inferior infarction, no significant differences between the treatment and control groups were demonstrable with respect to global and regional left ventricular ejection fraction. Thus, intravenous administration of streptokinase within 6 h after the onset of symptoms of acute myocardial infarction preserves left ventricular function over a period of greater than or equal to 3 years in patients with acute anterior myocardial infarction. It improves regional myocardial function within the infarct zone as well as in remote areas. In patients with acute inferior myocardial infarction, benefit from intravenous streptokinase is of only minor degree.

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.

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.

Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activator.

To improve further the patency rate of infarct-related coronary arteries, the following accelerated dosage regimen of recombinant tissue-type plasminogen activator (rt-PA) was administered to 80 patients with acute myocardial infarction of less than or equal to 6 h duration: 15 mg intravenous bolus, 50 mg infusion over 30 min and 35 mg infusion over the following 60 min. After coronary angiography at 90 min coronary angioplasty was performed in 16 patients and additional thrombolysis in 3 patients. Six patients were not included in the final angiographic analysis, mostly because of borderline ST segment elevations, in order to avoid overestimation of the efficacy of this dose regimen. Four of these had a patent infarct artery; no early angiogram was performed on two. Sixty minutes after the start of infusion, 54 (74%) of 73 patients had a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) as did 67 (91%) of 74 patients at 90 min. At 24 h, 61 (92.4%) of 66 patients showed a patent infarct artery. Recurrent myocardial ischemia was noted in 12 patients, 7 (9.4%) of whom experienced reinfarction during the hospital stay. Minor local bleeding complications were observed in 14 patients (17.5%). There were four in-hospital cardiac deaths; one patient who underwent additional thrombolysis for recurrent ischemia died from bleeding complications. These results show that a rapid infusion of 100 mg of rt-PA over 90 min yields a high early patency rate of the infarct-related artery without an increase in reocclusion rate and adverse reactions.

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.

Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction.

Pharmacokinetics and fibrin specificity of alteplase (recombinant tissue-type plasminogen activator) were determined in 10 patients with acute myocardial infarction undergoing an accelerated infusion regimen during the alteplase/anistreplase patency study (TAPS). Fifteen milligrams of alteplase was administered as an intravenous bolus injection, followed by infusions of 50 mg over 30 min and 35 mg over a further 60 min. Mean steady state plasma concentrations of alteplase during the initial 30 min were 3.2 +/- 0.84 micrograms/ml, measured immunochemically, and 2.1 +/- 0.23 micrograms/ml, measured using a functional activity assay. These values were 45% and 51% higher, respectively, than those during the standard infusion schedule (p less than 0.01). However, the predominant plasma half-life determined by model fitting based on either assay (3.3 to 3.5 min) was unaltered compared with the standard regimen. Maximal concentrations of fibrin and fibrinogen degradation products were 5.1 +/- 2.2 and 1.9 +/- 1.1 micrograms/ml, respectively. Plasminogen decreased to 70% and alpha 2-antiplasmin to 35% of values before infusion. The results indicate that 1) improved coronary patency rates during "front-loaded" infusions can be rationalized in terms of higher plasma concentrations of both free and immunoreactive alteplase, 2) kinetic variables are comparable with those of other dosing strategies, and 3) fibrin specificity is not diminished relative to that of the standard infusion regimen.

Effects of thrombolytic therapy in acute inferior myocardial infarction with or without right ventricular involvement. HIT-4 Trial Group. Hirudin for Improvement of Thrombolysis.

OBJECTIVES: This study assessed the prognostic impact of right ventricular involvement (RVI) in streptokinase-treated patients with inferior acute myocardial infarction (AMI) stratified for small or large AMI. BACKGROUND: Only scant data exist from small studies about the impact of reperfusion therapy on survival in patients with RVI during inferior AMI. METHODS: Right ventricular involvement was assessed by ST-segment elevation > or =0.1 mV in lead V4R and infarct size by the extent of ST-segment deviation on the baseline electrocardiogram: small AMI=sum ST-segment elevation < or =0.8 mV and no precordial ST-segment depression (small ST); large AMI=presence of precordial ST-segment depression or sum ST-segment elevation >0.8 mV (large ST) in 522 inferior AMI patients of the Hirudin for Improvement of Thrombolysis (HIT-4) Trial. In 187 patients, 90-min coronary angiography was performed. RESULTS: Right ventricular involvement was present in 169 patients (32%). Higher 30-day cardiac mortality rates with RVI (5.9% vs. 2.5%) were related to larger infarct size rather than to RVI. For large ST, a proximal right coronary artery lesion was observed in 52% with and in 23% without RVI. Patency rates at 90 min were similar (54% vs. 52%). In the 28% of patients who had small ST, cardiac mortality was less than 1% irrespective of the presence of RVI. Coronary artery lesions were mostly located distally. Patency rates were 27% with and 80% without RVI. CONCLUSIONS: ST-segment elevation of > or =0.1 mV in V4R in inferior AMI patients is associated with larger infarct size and higher 30-day mortality rates. Right ventricular involvement is not an independent predictor of survival. In patients with small ST, cardiac mortality is low, even if ST V4R is > or =0.1 mV.

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. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK).

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.

Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS)

Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and anisoylated plasminogen streptokinase activator (APSAC) in myocardial infarction has been proved to reduce mortality. A new front-loaded infusion regimen of 100 mg of rt-PA with an initial bolus dose of 15 mg followed by an infusion of 50 mg over 30 min and 35 mg over 60 min has been reported to yield higher patency rates than those achieved with standard regimens of thrombolytic treatment. The effects of this front-loaded administration of rt-PA versus those obtained with APSAC on early patency and reocclusion of infarct-related coronary arteries were investigated in a randomized multicenter trial in 421 patients with acute myocardial infarction. Coronary angiography 90 min after the start of treatment revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) in 84.4% of 199 patients given rt-PA versus 70.3% of 202 patients given APSAC (p = 0.0007). Early reocclusion within 24 to 48 h was documented in 10.3% of 174 patients given rt-PA versus 2.5% of 163 patients given APSAC. Late reocclusion within 21 days was observed in 2.6% of 152 patients given rt-PA versus 6.3% of 159 patients given APSAC. There were 5 in-hospital deaths (2.4%) in the rt-PA group and 17 deaths (8.1%) in the APSAC group (p = 0.0095). The reinfarction rate was 3.8% and 4.8%, respectively. Peak serum creatine kinase and left ventricular ejection fraction at follow-up angiography were essentially identical in both treatment groups. There were more bleeding complications after APSAC (45% vs. 31%, p = 0.0019).(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolysis with recombinant unglycosylated single-chain urokinase-type plasminogen activator (saruplase) in acute myocardial infarction: influence of heparin on early patency rate (LIMITS study). Liquemin in Myocardial Infarction During Thrombolysis With Saruplase.

OBJECTIVES: The Liquemin in Myocardial Infarction During Thrombolysis With Saruplase (LIMITS) study was instituted to evaluate and characterize the effect of a prethrombolytic heparin bolus (5,000 IU) on the efficacy and safety of saruplase in patients with acute myocardial infarction. BACKGROUND: Heparin has been used after thrombolytic therapy for acute myocardial infarction to prevent reocclusion of the infarct-related artery. METHODS: The study was designed as a randomized, parallel-group, double-blind, multicenter trial. Patients were treated within 6 h of onset of symptoms with either a bolus of 5,000 IU of heparin (Liquemin) (n = 56, HSH group) or placebo (n = 62, PSH group) before thrombolytic treatment with saruplase given as a 20-mg bolus followed by an infusion of 60 mg over 60 min. Thirty minutes after completion of thrombolysis, an intravenous heparin infusion was administered for 5 days. Before coronary angiography was performed at 6 to 12 h after start of lysis, an additional bolus of 5,000 IU heparin was given to all patients. End points studied were patency of the infarct-related artery, changes in the hemostatic system and bleeding complications. RESULTS: In the HSH group (heparin-saruplase-heparin), 78.6% of patients had an open infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 or 3) compared with 56.5% in the PSH group (placebo-saruplase-heparin) (intention-to-treat analysis, p = 0.01). No significant difference was observed between the two groups with regard to changes in fibrinogen and fibrin/fibrinogen degradation products. A total of eight bleeding complications (14.3%) were observed in the HSH group and five (8.1%) in the PSH group; no cerebrovascular event occurred, and no allergic reaction was reported. A total of 12 patients died during the hospital stay, 3 in the HSH group (5.4%) and 9 in the PSH group (14.5%). CONCLUSIONS: In acute myocardial infarction, the administration of a heparin bolus before thrombolytic therapy with saruplase is associated with a significantly higher patency at angiography 6 to 12 h after the start of thrombolysis without any appreciable increase in risk of bleeding.

Intravenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarction: results of the German Activator Urokinase Study (GAUS).

The effects of recombinant tissue plasminogen activator (rt-PA) and urokinase on patency and early reocclusion of infarct-related coronary arteries were investigated in a single blind, randomized multicenter trial in 246 patients with acute myocardial infarction of less than 6 h duration. Both 70 mg of single chain rt-PA with an initial bolus of 10 mg and 3 million units of urokinase with an initial bolus of 1.5 million units were given intravenously over 90 min. The first angiographic study at the end of the infusion revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 69.4% of 121 patients given rt-PA versus 65.8% of 117 patients given urokinase (p = NS). Among patients treated within 3 h from symptom onset a patent infarct-related artery was found in 63.9% of 72 patients given rt-PA versus 70% of 70 patients given urokinase (p = NS). There were five cardiac deaths in each group and one fatal intracranial hemorrhage in the rt-PA group. The in-hospital reinfarction rate was 8.9% versus 13.2% for patients treated with rt-PA and urokinase, respectively. There was no difference in left ventricular function at baseline and follow-up catheterization studies. Both drugs were well tolerated and there was no significant difference in cardiovascular or bleeding complications between the two groups. It is concluded that rt-PA and urokinase in the dosages used provide similar efficacy and safety in the treatment of acute myocardial infarction. Reocclusion during the first 24 h may be less frequent after urokinase treatment.

The Na(+)/H(+) exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial.

OBJECTIVES: We conducted an international, prospective, randomized, double-blind, placebo-controlled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarction (MI) to investigate the effect of eniporide on infarct size and clinical outcome. BACKGROUND: Experimental studies suggest that the activity of the Na(+)/H(+) exchange (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform and has been shown to limit infarct size in experimental models. METHODS: The primary efficacy end point was the infarct size measured by the cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha-HDBH) (area under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eniporide given as a 10-min infusion before start of reperfusion therapy were compared with placebo in 430 patients, and in stage 2, 100 and 150 mg eniporide were compared with placebo in 959 patients. RESULTS: In stage 1, the administration of 100 mg and 150 mg eniporide resulted in smaller infarct sizes (mean alpha-HBDH AUC in U/ml x h, placebo: 44.2, 100 mg eniporide: 40.2, 150 mg eniporide: 33.9), especially in the angioplasty group. In contrast, in stage 2 there was no difference in the enzymatic infarct size between the three groups (placebo: 41.2, 100 mg eniporide: 43.0, 150 mg eniporide: 41.5). Overall there was no effect of eniporide on clinical outcome (death, cardiogenic shock, heart failure, life-threatening arrhythmias). However, there was a significant reduction of the incidence of heart failure in patients reperfused late (>4 h). CONCLUSIONS: In this large study administration of the NHE-1 inhibitor eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.