Acute Coronary Syndromes and Percutaneous Coronary Interventions: impact of bleeding and blood transfusion.

Activation of the coagulation cascade and platelet functions occurs in ACS and may lead to subsequent thrombus formation, vessel occlusion, distal embolisation, myocardial ischaemia, necrosis and eventually death. Over the last 20 years, the outcome of ACS and PCI patients has considerably improved, thanks to better pharmacologic environment, urgent reperfusion in STEMI (ST elevation myocardial infarction), timely revascularisation in non-ST elevation ACS (NSTEACS) and improved PCI techniques, particularly widespread use of stents. In this context, bleeding was long considered as inherent to the modern therapeutic approach and without real consequences. Actually, bleeding has a strong impact on outcome, with a four- to five-fold increase in the rate of death, myocardial infarction and stroke at 30 days and six months. In addition, blood transfusion may have deleterious effects. Recent evidence shows that reduced risk of bleeding leads to a reduced risk of ischemic events (death, myocardial infarction and stroke). The exact mechanisms by which bleeding impacts on outcome are as yet poorly understood. The interruption of active treatment may play an important role. Activation of coagulation or inflammation in case of bleeding, and depletion of 2,3DPG and nitric oxide, inflammatory and immunologic reactions triggered by blood transfusion, are among the potential mechanisms. Prevention of bleeding has become as important as prevention of ischaemic events. Risk stratification for bleeding is as important as overall risk stratification for further ischaemic events. In patients at high risk of bleeding, appropriate choice and dosage of drugs, combinations of drugs, and the use of radial rather than femoral approach are essential components of bleeding prevention.

[Evaluation of management of infarction in the Franche Comté province by the use of the Franche Comté Cardiology Registry, May 2005-May 2006]. / L'évaluation des pratiques professionnelles pour la prise en charge des infarctus en Franche-Comté. Expérience d'une évaluation à l'échelle régionale par l'utilisation des données du registre franc-comtois de cardiologie, mai 2005-mai 2006.

RATIONALE: The management of acute infarction often necessitates a network of organisation between different centres, thus making it the object of an evaluation of professional practices (EPP). We report the experience in the Franche Comté province of an EPP at a regional level in the management of infarction. METHODS: All of the patients admitted to 10 of the 11 centres in the region were included in a prospective survey. Quality indicators for acute and chronic care were defined, as well as scores, on the basis of use of treatments specified in guidelines. RESULTS: Between May 2005 and May 2006, 1,170 patients were admitted. The patients' risk levels and quality scores were calculated. The rate of use of the quality indicators was higher in our survey than that observed in all of the published studies, except for the use of betablockers. The quality of care could therefore be considered as highly satisfactory. Comparison between the centres revealed some differences. Even after adjustment for the risk score on admission, the quality score for acute care was related to mortality at 1 month. CONCLUSIONS: An EPP is possible for the management of infarction, on a regional scale such as in the province of Franche Comté. The acute quality score turned out to be an independent factor for mortality. The indicators showed that the quality of care was highly satisfactory, even though more progress could be made in the prescription of betablockers.

Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction.

Definition of MI. Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: a) ischemic symptoms; b) development of pathologic Qwaves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); or d) coronary artery intervention (e.g., coronary angioplasty). 2) Pathologic findings of an acute MI. Criteria for established MI. Any one of the following criteria satisfies the diagnosis for established MI: 1) Development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed. 2) Pathologic findings of a healed or healing MI.

Long-term results of percutaneous aortic valvuloplasty compared with aortic valve replacement in patients more than 75 years old.

OBJECTIVES AND BACKGROUND: To assess the long-term results of percutaneous aortic valvuloplasty and aortic valve replacement in elderly persons, two similar nonrandomized series of patients greater than or equal to 75 years old treated by one or the other method between January 1986 and March 1989 in the same institution were compared. METHODS: Forty-six patients, 23 men and 23 women, with a mean age of 79.7 +/- 3.6 years (range 75 to 90) underwent percutaneous aortic valvuloplasty with use of the Cribier method (group 1). Twenty-three additional patients, 14 men and 9 women with a mean age of 78.4 +/- 2.4 years (range 75 to 86) underwent aortic valve replacement with a bioprosthesis (group 2). All of them suffered from severe calcified aortic stenosis. Clinical and hemodynamic status were similar in both groups. The mean follow-up period was 21.5 months (5 days to 60 months) in group 1 and 27.5 months (7 days to 61 months) in group 2. RESULTS: Three patients (6.5%) in group 1 died within 5 days after percutaneous aortic valvuloplasty; 24 patients (52%) died during the follow-up period, 16 of whom died of recurrent cardiac failure. Of 16 patients (35%) subsequently operated on at an average of 15.8 months after percutaneous aortic valvuloplasty, 2 died at operation. Only three group 1 patients (6.5%) are still alive without subsequent aortic valve replacement. In group 2, two patients (8.7%) died postoperatively and three (13%) died during the follow-up period. All other patients (78%) are still alive and in New York Heart Association functional class I or II. The overall survival rate in group 1 was 75% at 1 year, 47% at 2 years and 33% at 5 years. In group 2, the survival rate was 83% at 1 and 2 years and 75% at 3 and 4 years. CONCLUSIONS: The results of percutaneous aortic valvuloplasty do not compare favorably with those of surgery in elderly people, and this treatment should not be recommended.

Safety of thrombolytic therapy in elderly patients with massive pulmonary embolism: a comparison with nonelderly patients.

OBJECTIVES: The aim of the study was to prospectively estimate the safety of thrombolytic therapy in elderly patients with massive pulmonary embolism in comparison with that in nonelderly patients. BACKGROUND: In massive pulmonary embolism, lysis of thrombi can be achieved faster with thrombolytic therapy than with conventional heparin therapy, but it is administered with great caution in elderly patients because the risk of bleeding is thought to be higher than in nonelderly patients. Yet, thrombolytic therapy might be of value in elderly patients also, in allowing potentially more rapid improvement than is achieved with conventional heparin therapy. METHODS: Eighty-nine patients with massive pulmonary embolism defined as Miller score > or = 17/34 underwent thrombolytic therapy without consideration of age if they had no contraindication for such treatment. Fifty-three patients were < or = 70 years old (mean age +/- SD 54 +/- 15 years; range 18 to 70), and 36 patients were > or = 71 years old (78 +/- 5 years; range 71 to 88). Except for mean age, there were no significant differences between the two treatment groups, particularly in terms of clinical presentation, average Miller score and pulmonary artery pressure regimen. Thrombolytic therapy was administered in the form of streptokinase at a dose of 100,000 IU/h over 12 h, with an initial injection of 250,000 IU over 15 min. Heparin was introduced 12 h after initiation of thrombolytic therapy. Urokinase or tissue-type plasminogen activator was used only in case of contraindication to streptokinase. RESULTS: The frequency of uncomplicated clinical course was the same in both treatment groups. Surgical embolectomy was necessary in three nonelderly patients (5.6%) and one elderly patient (2.7%). Changes in pulmonary pressure regimen and Miller score were identical in both groups. Three patients died during the in-hospital course: two nonelderly patients (3.7%) and one elderly patient (2.7%). Minor bleeding occurred in five nonelderly (9.4%) and five elderly (13.8%) patients (p = 0.74). Major bleeding was observed in three nonelderly (5.6%) and five elderly (13.8%) patients (p = 0.29). Bleeding subsequent to early invasive procedure accounted for six (75%) of eight patients with major bleeding: two nonelderly patients (one of whom died) and four elderly patients. No intracranial hemorrhage was observed. No predisposing factor for bleeding was identified, except the need for early vascular access for pulmonary angiography through the femoral approach or for percutaneous insertion of an intracaval device for partial interruption of the inferior vena cava. CONCLUSIONS: Thrombolytic therapy administered for massive pulmonary embolism in patients free of contraindication yields similar results and carries a similar risk for bleeding complications in elderly compared with nonelderly patients. Limiting early invasive procedures may result in less frequent major bleeding complications.

The double-balloon and Inoue techniques in percutaneous mitral valvuloplasty: comparative results in a series of 232 cases.

Immediate hemodynamic results of percutaneous mitral valvuloplasty were compared in two consecutive series of unselected patients from the same institution undergoing valvuloplasty with the double-balloon (161 patients) or the Inoue balloon (71 patients) technique. Before valvuloplasty, the patient series were comparable with regard to average age, gender repartition and most clinical, electrocardiographic, X-ray and hemodynamic variables. Poor anatomic forms of mitral stenosis were equally distributed in both series (41% vs. 45%, p = NS). The magnitude of mitral valve area increase and of mean mitral gradient decrease during percutaneous mitral valvuloplasty did not differ significantly in the Inoue balloon and double-balloon series (mean +/- SEM 1.1 +/- 0.2 to 1.95 +/- 0.5 and 1.0 +/- 0.2 to 1.97 +/- 0.5 cm2, respectively, for mitral valve area and 12 +/- 3 to 5 +/- 2 and 13 +/- 4 to 5 +/- 2 mm Hg, respectively, for mean mitral gradient). Four cases of 3+ mitral regurgitation occurred in the Inoue balloon series and 7 in the double-balloon series (p = NS). A good immediate result--defined as mitral valve area greater than or equal to 1.5 cm2 with greater than or equal to 25% in mitral valve area gain and mitral regurgitation less than 2+ at the end of the procedure--was observed in 78% of patients in both series. Three cases of tamponade due to chamber perforation and 14 cases of transient air embolism in the right coronary system due to balloon rupture were observed in the double-balloon series.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: a European multicenter double-blind trial. The European Cooperative Study Group for Pulmonary Embolism.

Twelve centers participated in a double-blind study in which 63 patients with angiographically documented acute massive pulmonary embolism were randomly assigned to treatment with either urokinase (4,400 U/kg as an intravenous bolus infusion, then 4,400 U/kg per h over 12 h; n = 29) or alteplase (10 mg as an intravenous bolus infusion, then 90 mg over 2 h) followed by heparin (n = 34). The primary objective was to compare the resolution of pulmonary embolism as judged by the change in total pulmonary resistance over the initial 2 h. Further objectives were to evaluate the changes in total pulmonary resistance over the next 10 h and the degree of angiographic resolution at 12 to 18 h. At 2 h, total pulmonary resistance decreased by 18 +/- 22% in the urokinase group and by 36 +/- 17% in the alteplase group (p = 0.0009). Continuous monitoring of pulmonary artery mean pressure, cardiac index and total pulmonary resistance revealed that these variables improved faster in the alteplase group, with consistently significant intergroup differences from 30 min up to 3 to 4 h. After 12 h, the decrease in total pulmonary resistance was 53 +/- 19% in the urokinase group compared with 48 +/- 17% in the alteplase group and the reduction in the angiographic severity score was 30 +/- 25% compared with 24 +/- 18%, respectively, with no significant intergroup differences. Bleeding was equally frequent in the two treatment groups, except that more urokinase-treated patients experienced hematomas at puncture sites.

Impact of intravascular ultrasound guidance in stent deployment on 6-month restenosis rate: a multicenter, randomized study comparing two strategies--with and without intravascular ultrasound guidance. RESIST Study Group. REStenosis after Ivus guided STenting.

OBJECTIVES: We aimed to investigate the impact of intravascular ultrasound (IVUS)-guided stent implantation on the 6-month restenosis rate, which has not yet been fully established in randomized trials. BACKGROUND: The 6-month angiographic restenosis rate was compared in patients with symptomatic ischemic heart disease who were randomly allocated to angioplasty and stent deployment, with versus without IVUS guidance. METHODS: After successful stent implantation, patients were randomized into two groups: Group A had no further dilation, and Group B had additional balloon dilation until achievement of IVUS criterion for stent expansion. The study group consisted of 164 patients, assuming a 50% reduction of the restenosis rate in Group B (15% vs. 30%) (alpha = 10%, beta = 20%). RESULTS: We enrolled 155 patients. Overdilation was carried out in 31 (39%) of 79 Group B patients, with the IVUS criterion being achieved in 63 (80%) of 79. No significant difference was observed in the minimal luminal diameter (MLD), but the stent lumen cross-sectional area (CSA) was significantly larger in Group B (mean +/- SD) (7.16 +/- 2.48 vs. 7.95 +/- 2.21 mm2, p = 0.04). At 6 months, there was no significant difference in the restenosis rate, (28.8% [21 of 73] in Group A vs. 22.5% [16 of 71] in Group B, p = 0.25), but according to the observed difference in the restenosis rate, the power of the study was only 40%. The difference in MLD was also nonsignificant (1.60 +/- 0.65 mm in Group A vs. 1.70 +/- 0.64 mm in Group B, p = 0.20), whereas the lumen CSA was 20% larger in the IVUS-guided group (4.47 +/- 2.59 vs. 5.36 +/- 2.81 mm2, p = 0.03). Lumen CSA was the only predictor of restenosis by multivariate logistic regression analysis. CONCLUSIONS: A nonsignificant 6.3% absolute reduction in the restenosis rate and a nonsignificant difference in MLD were observed in this study. Nonetheless, we still cannot rule out a beneficial effect of IVUS guidance, although this may have gone undetected owing to a lack of statistical power. A significant increase was observed in immediate and 6-month lumen size, as detected by IVUS, indicating that ultrasound guidance in stent deployment may be beneficial.

Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and one-year follow-up.

OBJECTIVES: This study sought to compare the efficacy of 2-h regimens of alteplase and streptokinase in acute massive pulmonary embolism. The primary end point was immediate hemodynamic improvement, and secondary end points included early clinical efficacy and safety, as well as 1-year clinical outcome. BACKGROUND: Several thrombolytic regimens have been compared for the past 10 years in randomized studies, showing that 2-h infusion regimens of alteplase or urokinase lead to faster hemodynamic improvement than former 12- to 24-h administration protocols in acute massive pulmonary embolism. Many trials have focused on immediate hemodynamic and angiographic outcomes, but none has addressed long-term follow-up after thrombolysis. METHODS: Sixty-six patients with acute massive pulmonary embolism (Miller score > 17 and mean pulmonary artery pressure >20 mm Hg) were randomly assigned to receive either a 100-mg 2-h infusion of alteplase (n = 23) or 1.5 million IU of streptokinase over 2 h (n = 43). In both groups, heparin infusion was started at the end of thrombolytic infusion and adapted thereafter. Total pulmonary resistance was monitored over a 12-h period. Pulmonary vascular obstruction was assessed 36 to 48 h after thrombolytic therapy. One-year follow-up information included death, cause of death, recurrent pulmonary embolism, chronic thromboembolic pulmonary hypertension, stroke and bleeding. RESULTS: Both groups had similar baseline angiographic and hemodynamic characteristics of severity, with maintained cardiac output in 64 (97%) of 66 patients. The results (mean +/- SD) demonstrated that despite a faster total pulmonary resistance improvement observed at 1 h in the alteplase group compared with the streptokinase group (33+/-16% vs. 19 16%, p = 0.006), a similar hemodynamic efficacy was obtained at 2 h when both thrombolytic regimens were completed (38+/-18% vs. 31+/-19%). There was no significant difference in either pulmonary vascular obstruction at 36 to 48 h or bleeding complication rates. One-year event-free survival was similar in both groups, as most events were related to concomitant diseases. CONCLUSIONS: These results suggest that a 2-h regimen of streptokinase can be routinely used in patients with massive pulmonary embolism and maintained cardiac output without obviously compromising efficacy or safety.

Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: effects on infarct size and left ventricular function.

Two hundred thirty-one patients with a first acute myocardial infarction were randomly allocated within 5 h after the onset of symptoms either to treatment with anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 min, or to conventional heparin therapy, 5,000 IU in a bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. One hundred twelve patients received APSAC and 119 received heparin within a mean period of 188 +/- 62 min after the onset of symptoms. Both groups were similar in age, location of the acute myocardial infarction, Killip functional class and time of randomization. Elective coronary arteriography was performed on an average of 4 +/- 1.2 days after initial therapy. Follow-up radionuclide angiography and thallium-201 single photon emission computed tomography were performed before hospital discharge. Infarct size was estimated from single photon emission computed tomography and expressed as a percent of total myocardial volume. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC group than in the heparin group. This was true for the entire study group (0.53 +/- 0.13 versus 0.47 +/- 0.12; p = 0.002) as well as for the subgroups of patients with anterior and inferior wall infarction (0.47 +/- 0.13 versus 0.40 +/- 0.11; p = 0.04 and 0.56 +/- 0.10 versus 0.51 +/- 0.11; p = 0.02, respectively). At 3 weeks, the difference remained significant for the anterior myocardial infarction subgroup. A significant 31% reduction in infarct size was found in the APSAC group (33% for the anterior infarction subgroup [p less than 0.05] and 16% for the inferior infarction subgroup [p = NS]). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = -0.73, p less than 0.01). By the end of a 3 week follow-up period, seven APSAC-treated patients and six heparin-treated patients had died. In conclusion, the early infusion of APSAC in acute myocardial infarction produced a high early patency rate, significant limitation of infarct size and significant preservation of left ventricular systolic function, mainly in anterior wall infarction.

Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty. The PREDICT Trial Investigators. Prevention of Restenosis by Elisor after Transluminal Coronary Angioplasty.

OBJECTIVES: This study sought to determine whether pravastatin affects clinical or angiographic restenosis after coronary balloon angioplasty. BACKGROUND: Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. METHODS: In a multicenter, randomized, double-blind trial, 695 patients were randomized to receive pravastatin (40 mg/day) or placebo for 6 months after successful balloon angioplasty. All patients received aspirin (100 mg/day). The primary angiographic end point was minimal lumen diameter (MLD) at follow-up, assessed by quantitative coronary angiography. A sample size of 313 patients per group was required to demonstrate a difference of 0.13 mm in MLD between groups (allowing for a two-tailed alpha error of 0.05 and a beta error of 0.20). To allow for incomplete angiographic follow-up (estimated lost to follow-up rate of 10%), 690 randomized patients were required. Secondary end points were angiographic restenosis rate (restenosis assessed as a categoric variable, > 50% stenosis) and clinical events (death, myocardial infarction, target vessel revascularization). RESULTS: At baseline, clinical, demographic, angiographic and lipid variables did not differ significantly between groups. In patients treated with pravastatin, there was a significant reduction in total and low density lipoprotein cholesterol and triglyceride levels and a significant increase in high density lipoprotein cholesterol levels. At follow-up the MLD (mean +/- SD) was 1.47 +/- 0.62 mm in the placebo group and 1.54 +/- 0.66 mm in the pravastatin group (p = 0.21). Similarly, late loss and net gain did not differ significantly between groups. The restenosis rate (recurrence > 50% stenosis) was 43.8% in the placebo group and 39.2% in the pravastatin group (p = 0.26). Clinical restenosis did not differ significantly between groups. CONCLUSIONS: Although pravastatin has documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, this study shows that it has no effect on angiographic outcome at the target site 6 months after coronary angioplasty.

Isotopic findings in anomalous origin of the left coronary artery from the pulmonary artery: report of an adult case.

Anomalous origin of the left coronary artery from the main pulmonary trunk results in myocardial ischemia or infarction, and may be a cause of death in the first months of life. Some patients, however, develop satisfactory coronary collateral circulation and remain asymptomatic into adulthood. In these patients, myocardial perfusion and left ventricular function are not well understood. We report the case of a 17-yr-old female patient, suffering from anomalous origin of the left coronary artery from the main pulmonary trunk, who underwent reimplantation of the left coronary artery to the aorta. The preoperative permanent 201Tl defect of the left antero-lateral ventricular wall and the abnormal regional wall motion induced by stress exercise testing were fully reversed after the operation.

A pilot study of subcutaneous recombinant hirudin (HBW 023) in the treatment of deep vein thrombosis.

BACKGROUND: Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the safety of a recombinant hirudin (HBW 023) administered subcutaneously in patients suffering from deep vein thrombosis. METHODS: Recombinant hirudin (HBW 023) was administered subcutaneously to 10 patients with recent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twice daily for 5 days, after which standard heparin and acenocoumarol were introduced. Bilateral lower limb venography, and pulmonary angiography, and/or ventilation-perfusion lung scan were carried out on day 1 prior to recombinant hirudin injection and repeated on day 5. aPTT and recombinant hirudin plasma levels were serially assessed after the 1st and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antithrombin III complexes, fibrin degradation products were collected on days 1 and 5. RESULTS: Clinical evolution was uneventful in all but one patient who had a probable recurrence of pulmonary embolism on day 4. No hemorrhagic complication, no untoward biological event was observed. On days 5, Marder score was unchanged or had decreased. Plasma levels of recombinant hirudin peaked in between 3 and 4 h following the injection. aPTT values paralleled, and were significantly correlated with plasma levels of recombinant hirudin on day 1 as well on day 5 (r = 0.903, r = 0.948 respectively). Fragment 1 + 2, and thrombin antithrombin complexes non-significantly decreased from day 1 to day 5. CONCLUSIONS: Subcutaneous administration of recombinant hirudin ensures prolonged stable plasma levels of recombinant hirudin which results in efficient anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.

Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent--a pilot study in the setting of coronary angioplasty.

AIM OF THE STUDY: To assess the antithrombotic properties of SR90107/ORG31540. a sulfated pentasaccharide, which enhances specifically antithrombin III mediated inactivation of factor-Xa, in a clinical setting known to promote arterial thrombosis, i.e. coronary angioplasty. METHODS AND RESULTS: Percutaneous transluminal coronary angioplasty (PTCA) was carried out with conventional balloons with a single 5 min intravenous infusion of 12 mg pentasaccharide, and 500 mg intravenous aspirin. Heparin was not allowed before, during PTCA, and within 24 h after PTCA. The primary end point was the rate of abrupt vessel closure during and within 24 h after the procedure. The sample size was set at 60 evaluable patients, in order to be able to conclude with a good level of confidence (>95%) that the abrupt vessel closure rate was less than 10%, if less than 3 abrupt vessel closures were observed. Seventy-one patients were included in the study, of whom 10 needed elective stenting, and were not considered as evaluable for efficacy. Two out of the 61 remaining evaluable patients experienced acute vessel closure during the study period [3.28%, 95% confidence interval (0.4%; 11.4%)]. No major bleeding occurred. The drug plasma concentrations reached 1.91+/-0.39 mg/], 10 min after pentasaccharide injection, and decreased on average to 1. 18+/-0.27 mg/l at 2 h, and to 0.36+/-0.11 mg/l at 23 h after administration of pentasaccharide. Activated clotting time (ACT) and activated partial thromboplastin (aPTT) time remained within normal range. Thrombin-antithrombin complex levels fell from 22+/-17.1 to 4.5+/-3.4 microg/ml, prothrombin fragment 1+2 levels decreased from 2.15+/-1.01 to 1.73+/-0.87, and activated factor VII levels decreased from 43.4+/-16.8 mU/ml to 18.9+/-7.3 mU/ml respectively from baseline to 2 h following injection of the tested drug. CONCLUSIONS: Administration of pentasaccharide led to the inhibition of thrombin generation without modification of aPTT and ACT. The rate of abrupt vessel closure was within range of rates reported in historical series. Thus we conclude that the anti-thrombotic activity of pentasaccharide, as shown in this pilot trial in the setting of coronary angioplasty, deserves further investigation.

Subcutaneous recombinant hirudin (HBW 023) versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective dose-ranging randomized trial. International Multicentre Hirudin Study Group.

The aim of this multicentre, prospective, randomised, dose-ranging study was to compare the safety and efficacy of subcutaneous recombinant hirudin (HBW 023) against intravenous sodium heparin in acute lower limb deep venous thrombosis (DVT). Patients were randomized to treatment with either HBW 023 or heparin for 5 +/- 1 days. HBW 023 was given according to body-weight in three dose groups. Thromboembolic disease was assessed by phlebography and ventilation/perfusion (V/Q) scanning on Day 1 and Day 5 +/- 1. One hundred and fifty-five patients were enrolled, of these 121 were evaluable for efficacy analysis. Significantly fewer patients on HBW 023 developed new V/Q abnormalities during the treatment period, (p = 0.006). There was no difference between the groups in thrombus extension or regression, major bleeding complications or serious adverse events. There were significantly fewer findings of new V/Q mismatch after treatment with HBW 023, and anticoagulant control was superior in these patients.

Balloon angioplasty versus rotational angioplasty in chronic coronary occlusions (the BAROCCO study).

Chronic total coronary occlusion remains one of the limitations of percutaneous transluminal coronary angioplasty, and few therapeutic devices are specifically designed to address this problem. Among such devices, low-speed rotational angioplasty could improve the primary success rate of the procedure but has never been studied in a controlled trial. One hundred consecutive patients with total coronary occlusion (duration 10 days to 1 year) and an indication for myocardial revascularization were randomized to either rotational or conventional angioplasty if the occlusion morphology was judged suitable for either technique. All baseline variables were evenly distributed among the 2 groups. The primary success rate in the rotational angioplasty groupø was 66% (33 of 50) compared with 52% (26 of 50) in the conventional angioplasty group before crossover to the rotational technique (p=NS). According to lesion morphology, the respective primary success rates were 77% (10 of 13) versus 92% (11 of 12) for tapered occlusions (p=NS), and 61% (22 of 36) versus 38% (14 of 37) for "stump-like" occlusions (p < 0.05). After taking into account the crossovers after failed conventional angioplasty, there was no benefit in performing rotational angioplasty first versus conventional angioplasty first (primary success rates 66% vs 60%, p=NS). Thus, in chronic coronary occlusions of tapered morphology, rotational angioplasty is not superior to conventional angioplasty. In stump-like occlusions, the primary success rate is higher with the rotational angioplasty technique; however ther is a disadvantage in using rotational angioplasty as a second-line device if the conventional technique is unsuccessful.

Use of left ventricular function as an end point of thrombolytic therapy.

In recent acute myocardial infarction, early reperfusion of the infarct-related artery by intracoronary or intravenous thrombolytic therapy induces a significant limitation of infarct size, provided reperfusion occurs within a time frame that myocardial salvage can still be expected. Limitation of infarct size reduces scar tissue formation, aneurysm formation, infarct zone expansion, left ventricular volume enlargement, and eventually results in higher left ventricular ejection fraction. Infarct size limitation and left ventricular function preservation occur with all thrombolytic agents currently in clinical use: streptokinase, alteplase and, more recently, anistreplase. When anistreplase is compared with conventional heparin therapy, a 31% reduction in infarct size is found (estimated from single photon emission computed tomography, or SPECT). This translates into a significant preservation of left ventricular ejection fraction as observed in anistreplase-treated patients compared with heparin-treated patients (0.53 +/- 0.13 vs 0.47 +/- 0.12, p less than 0.002). In comparative trials of 2 thrombolytic agents, anistreplase was demonstrated to be as efficient as alteplase on left ventricular ejection fraction preservation and infarct size limitation.

Limitation of myocardial infarct size and preservation of left ventricular function by early administration of APSAC in myocardial infarction.

In cases of acute myocardial infarction (MI), it has been shown that preserving left ventricular function and limiting infarct size with early reperfusion of the occluded artery by means of a thrombolytic agent could eventually result in a reduced mortality rate. The aim of the APSIM study (anisoylated plasminogen streptokinase activator complex [APSAC] dans l'infarctus du Myocarde) was to demonstrate that early administration of APSAC in patients with recent acute MI could limit the infarct size and preserve left ventricular systolic function. In all, 231 patients with a first acute MI were randomly allocated to either APSAC (30 U over 5 minutes) or to conventional heparin therapy (5,000 IU in bolus injection) within 5 hours of the onset of symptoms. Of these patients, 112 received APSAC and 119 received heparin within a mean period of 188 +/- 62 minutes after the onset of symptoms. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC than in the heparin group. This was true for the entire population (0.53 +/- 0.13 vs 0.47 +/- 0.13, p = 0.002) as well as for the subgroups of anterior and inferior wall infarctions (0.47 +/- 0.13 vs 0.4 +/- 0.16, p = 0.004 and 0.56 +/- 0.11 vs 0.51 +/- 0.09, p = 0.02). At 3 weeks, the difference remained significant for patients with anterior MI.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of early high-dose streptokinase intravenously on left ventricular function in acute myocardial infarction.

One hundred seven patients who recently had acute myocardial infarction were randomly assigned either to standard heparin therapy or to intravenous streptokinase within 5 hours after the onset of symptoms in 7 hospitals without catheterization facilities. In the third week, the patients were referred to a university hospital, where the patency rate of the infarct-related artery was studied by selective coronary arteriography and left ventricular function by radionuclide angiography. Fifty-five patients received heparin and 52 streptokinase within a mean period of 190 minutes after the onset of symptoms. Seven patients in the heparin group and 4 in the streptokinase group died in hospital. The patency rate of the infarct-related artery was identical in both groups (69% in the heparin group vs 68% in the streptokinase group). Left ventricular ejection fraction was not statistically different (0.44 +/- 0.13 in the heparin group vs 0.45 +/- 0.12 in the streptokinase group). Left ventricular ejection fraction was significantly higher in patients with a patent infarct-related artery than in patients with an obstructed infarct-related artery (0.49 +/- 0.12 vs 0.41 +/- 0.15, p less than 0.01). In patients with inferior wall infarction, left ventricular ejection fraction was identical (0.50 +/- 0.10 in the heparin group vs 0.52 +/- 0.09, in the streptokinase group). In patients with anterior wall infarction, left ventricular ejection fraction was significantly higher in the streptokinase group than in heparin group (0.40 +/- 0.10 vs 0.33 +/- 0.09, p less than 0.05). Analysis of regional wall motion revealed that improvement occurred in the lateral wall of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

False lumen patency as a predictor of late outcome in aortic dissection.

Aortic dissection (AD) is a disease with a high-risk of mortality. Late deaths are often related to complications in nonoperated aortic segments. Between 1984 and 1996, we retrospectively analyzed the data of 109 patients with acute AD (81 men and 28 women; average age 61 +/- 14 years). All imaging examinations were reviewed, and a magnetic resonance imaging examination was performed at the time of the study. Aortic diameters were measured on each aortic segment. Predictive factors of mortality were determined by Cox's proportional hazard model, in univariate and multivariate analyses, using BMDP statistical software. Follow-up was an average of 44 +/- 46 months (range 24 to 164). Actuarial survival rates were 52%, 46%, and 37% at 1, 5, and 10 years, respectively, for type A AD versus 76%, 72%, and 46% for type B AD. Predictors of late mortality were age >70 years and postoperative false lumen patency of the thoracic descending aorta (RR 3.4, 95% confidence intervals 1.20 to 9.8). Descending aorta diameter was larger when false lumen was patent (31 vs 44 mm; p = 0.02) in type A AD. Furthermore, patency was less frequent in operated type A AD when surgery had been extended to the aortic arch. Thus, patency of descending aorta false lumen is responsible for progressive aortic dilation. In type A AD, open distal repair makes it possible to check the aortic arch and replace it when necessary, decreases the false lumen patency rate, and improves late survival.