[Current indications for cardiac MR imaging]. / Indications cliniques appropriées de l'IRM en pathologie cardio-vasculaire.

MRI has acquired over the years a role in the evaluation of cardiovascular pathology especially with regards to its ability to assess right and left ventricular function and delayed postcontrast "viability" sequences. Current class I clinical indications include: viability for patients with ischemic cardiomyopathy and acute coronary syndrome, etiology and prognostic evaluation of non-ischemic cardiomyopathies including myocarditis and arrhytmogenic right ventricular cardiomyopathy, chronic pericarditis and cardiac masses, non-urgent aortic aneurysm and dissection, congenital cardiopathies: vascular malformations and follow-up after curative or palliative surgery. MRI provides a complete non operator dependent evaluation, and is particularly useful for follow-up since it may be repeated due to its absence of ionizing radiation

Optimal long-term antithrombotic treatment of patients with stable coronary artery disease and atrial fibrillation: "OLTAT registry".

BACKGROUND: The optimal long-term antithrombotic treatment of patients with stable coronary artery disease (CAD) and atrial fibrillation (AF) is a challenge in daily practice. We sought to determine the prevalence of hemorrhagic complications and ischaemic events depending on antithrombotic strategy in patients with stable CAD and AF. METHODS: The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of cardiovascular mortality, myocardial infarction and ischaemic stroke. The subsequent risks of MACCE and clinically significant bleedings requiring hospitalisation (major safety outcome) were analyzed in a propensity score-matched analysis by adjusted Cox regression models. RESULTS: Six hundred and six patients with high thrombotic and bleeding risks (mean age 73.4 ±â€¯9.8 years, 25.2% female, CHA2DS2-VASc score:4.7 ±â€¯1.5, and HAS-BLED score:3.1 ±â€¯1.0) were included, and 127 propensity-matched pairs were analyzed. At inclusion, 172 patients (28.4%) were on oral anticoagulation (OAC) alone (75.6% on VKA and 24.4% on DOAC) and 434 patients (71.6%) on OAC + single antiplatelet therapy (SAPT) (71.9% on VKA and 28.1% on DOAC). At 5-year follow-up, MACCE rate did not significantly differ in both groups (30.9% in OAC + SAPT vs. 26.8% in OAC alone; adjusted HR 1.1 [0.8-1.5], p = 0.58), but clinically significant bleedings (28.3% vs. 18.5%; adjusted HR 1.8 [1.2-2.8], p = 0.005) and total deaths (29.5% vs. 20.8%; adjusted HR 1.4 [95% CI 1.0-2.2], p = 0.049) were higher in patients with OAC + SAPT than in patients with OAC alone. CONCLUSIONS: In patients with stable CAD and AF, the addition of antiplatelet therapy to VKA or DOAC therapy was independently associated with a higher risk of bleeding and overall mortality, without significant reduction in cardiac and cerebral ischaemic events.

[The best of thrombosis in 2006]. / L'essentiel de 2006 en thrombose.

The year 2006 was an excellent year for trials publications on antithrombotic treatments. The results of several important trials were published. Firstly, two new antithrombotic molecules, fondaparinux (anti-Xa) and bivalirudine (anti-IIa), were the object of large scale trials, in coronary artery disease. Fondaparinux, in the OASIS-5 study, was compared with the reference treatment by enoxaparin. The efficacy was equivalent in the treatment of acute coronary syndromes without ST elevation, in the reduction of ischaemic events and, above all, was associated with a reduction in severe bleeding complications and reduced mortality at 9 days and 6 months. The ISAR-REACT 2 trial demonstrated the value of abciximab, a platelet membrane glycoprotein inhibitor, in the treatment of high risk acute coronary syndromes identified by the risk in troponin levels. The ACUITY trial showed that bivalirudine was as effective as abciximab in the treatment of acute coronary syndromes in terms of prevention of ischaemic events and that it reduced the number of bleeding complications. The CHARISMA trial looked at the possible benefit of biotherapy with clopidogrel and aspirin versus monotherapy with aspirin alone in a large panel of high cardiovascular risk patients. The globally negative results should, however, be closely analysed because some subgroups (symptomatic patients) were identified, in which a possible benefit was observed in contrast to other subgroups (multiple risk factors) in which biotherapy appeared to be deleterious. The results of other less publicised trials (STEEPLE, FIDO, ESPRIT) are also commented.

[The best of thrombosis in 2005]. / L'essentiel de 2005 en thrombose.

The year 2005 was rich in new information. Many articles were published on antithrombotic therapy, the key stone in the management of several cardiovascular diseases which are the cardiologists' "daily bread". Antithrombotic treatment is essential in the treatment of patients undergoing interventional coronary procedures. The loading dose of 300 mg clopidogrel has been questioned. The ARMYDA-2 trial showed that a loading dose of 600 mg of clopidogrel administered 4 to 8 hours before coronary angioplasty significantly reduced the number of peri-procedural myocardial infarctions without increasing the risk of bleeding complications. Other molecules such as prasugrel could provide an alternative to treatment with clopidogrel. The results of a phase 2 trial (JUMBO-TIMI 26) comparing clopidogrel and prasugrel have opened the way for a large scale phase 3 trial which is currently under way. In myocardial infarction, the CLARITY-TIMI 28 trial showed that patients under 75 years of age with acute myocardial infarction of less than 12 hours duration treated with aspirin and thrombolytic therapy had better results with respect to the combined criteria of patency of the culprit artery and ischaemic complications with the addition of clopidogrel. In the CREATE trial, patients with acute myocardial infarction had a lower mortality and recurrence of infarction without significantly increasing the risk of stroke with reviparin. The development of ximelagatran has been held up by a potentially serious hepato-toxicity. Two large-scale trials were published this year, one in atrial fibrillation and the other in venous thrombosis. In the former, the hypothesis of non-inferiority compared with well conducted oral anticoagulation with coumadine was supported and, in the latter, the hypothesis of non-inferiority compared with treatment with enoxaparin followed by warfarin was also confirmed despite a higher number of coronary events in the xinelagatran group. Another study which merits a citation showed that in patients with a previous history of aspirin-induced bleeding ulcers, the association of low dose aspirin and a proton pump inhibitor was superior to the prescription of clopidogrel in the prevention of recurrent bleeding. A study of the pharmacogenetics of coumadine and the variability of its dosage was also a valuable contribution. In the field of management of bleeding, a study demonstrated the potential benefits of treatment with VIIa recombinant factor.

[The value of active stents for coronary angioplasty in patients with chronic renal failure]. / Intérêt du stent actif dans l'angioplastie coronaire chez l'insuffisant rénal chronique.

UNLABELLED: The risk of intra-stent restenosis has diminished considerably with the advent of endoprostheses which actively release sirolimus or paclitaxel. Patients with chronic renal failure constitute a high cardiovascular risk population, in whom the incidence of coronary heart disease is particularly high, representing one of the principal causes of death. The aim of this study, which included 152 patients, was to quantify the value of active stents for coronary angioplasty in patients with chronic renal failure. Thirty eight patients with chronic renal failure who underwent angioplasty with active stents were matched for age, sex and the presence of diabetes with 3 other groups of patients: one group with active stents but without renal failure, one group with inactive stents and no renal failure, and one group with inactive stents and chronic renal failure. The average follow up was 16 +/- 5 months. The acute stent thrombosis rate (2%) was not elevated in cases of renal failure nor after active stent implantation. Chronic renal failure significantly increased the mortality rate 16 months after angioplasty, whichever type of stent was used: 8 versus 2% deaths in patients with an inactive stent (p = 0.001). In renal failure, the risk of death was lower with an active stent (8 vs 26% with an inactive stent, p<0.05). Similarly, there was a non-significant trend towards a lower risk of death and/or infarction in renal failure after active stents (8 vs 21% with an inactive stent, NS). CONCLUSIONS: In this study, coronary angioplasty with an active stent in patients with chronic renal failure was associated with a lower mortality rate compared with inactive stents, with no increase in the risk of acute thrombosis.

Atrial fibrillation after coronary artery bypass surgery: a model for preoperative risk stratification.

BACKGROUND: Atrial fibrillation (AF) occurs in 20% to 40% of patients after CABG. Identification of patients vulnerable for arrhythmia will allow targeting of those most likely to benefit from prophylactic therapy. The aim of the present study was to evaluate accuracy of a prospectively defined signal-averaged P-wave duration (SAPD) cutoff and additional preoperative characteristics for the prediction of AF after CABG. METHODS AND RESULTS: Patients undergoing elective isolated CABG were recruited to the present prospective study. SAPD was recorded in all patients. Filtered signals from 3 orthogonal leads were combined in a vector analysis, and total SAPD was measured preoperatively. Postoperative in-hospital AF occurred in 92 (28.2%) of 326 patients. Patients who developed AF were older (65.9 versus 61.7 years of age; P<0.0005) and had longer SAPD (158 versus 145 ms; P<0.0005) than non-AF patients. Incidence of AF increased in patients > or =75 years of age and increased progressively throughout the range of SAPD. Stepwise logistic regression analysis of preoperative variables identified that SAPD >155 ms (odds ratio, 5.37; 95% CI, 3.10 to 9.30; P<0.0005), advanced age (odds ratio, 1. 53; 95% CI, 1.26 to 1.86 per 5-year increase in age; P<0.0005), and male sex (odds ratio, 2.88; 95% CI, 1.30 to 6.40; P<0.01) independently predicted AF. Prospectively defined SAPD >155 ms predicted AF with positive and negative predictive accuracy of 49% and 84%, respectively. CONCLUSIONS: A combination of prolonged SAPD, advanced age, and male sex identifies patients at high risk for development of AF after CABG.

Noninvasive in vivo magnetic resonance imaging of experimental coronary artery lesions in a porcine model.

BACKGROUND: The ability to characterize and quantify coronary artery atherosclerotic lesions accurately, reproducibly, and noninvasively may allow the stratification of risk for future acute coronary syndromes and help direct therapeutic management. MRI has been shown to accurately characterize and quantify atherosclerosis; however, because of the combination of cardiac and respiratory motion artifacts, nonlinear course, and relatively small size of the coronary arteries, these techniques have not been able to be translated to the coronary system in vivo. METHODS AND RESULTS: Coronary lesions were induced in Yorkshire albino swine (n=6) with balloon angioplasty, and 4 weeks later MRI of the coronary artery lesions was performed. High-resolution in vivo images of the coronary artery wall and lesions were obtained with a double-inversion-recovery fast-spin-echo sequence in a 1.5-T MR system. There was good agreement between measurements of vessel wall thickness and area from MR images of the coronary arteries and the matched histopathology sections (n=43). The mean difference (MRI minus histopathology +/- SD) for mean wall thickness was 0.26+/-0.18 mm, and for vessel wall area, 5.65+/-3.51 mm(2). MRI was also able to visualize intralesion hematoma (sensitivity 82%, specificity 84%). CONCLUSIONS: Using a clinical MR system, we were able to image coronary artery lesions in vivo in an experimental porcine model. Further studies are needed to assess the ability of MRI to characterize coronary atherosclerotic lesions in vivo.

Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging.

BACKGROUND: High-resolution MRI has the potential to noninvasively image the human coronary artery wall and define the degree and nature of coronary artery disease. Coronary artery imaging by MR has been limited by artifacts related to blood flow and motion and by low spatial resolution. METHODS AND RESULTS: We used a noninvasive black-blood (BB) MRI (BB-MR) method, free of motion and blood-flow artifacts, for high-resolution (down to 0.46 mm in-plane resolution and 3-mm slice thickness) imaging of the coronary artery lumen and wall. In vivo BB-MR of both normal and atherosclerotic human coronary arteries was performed in 13 subjects: 8 normal subjects and 5 patients with coronary artery disease. The average coronary wall thickness for each cross-sectional image was 0.75+/-0.17 mm (range, 0.55 to 1.0 mm) in the normal subjects. MR images of coronary arteries in patients with >/=40% stenosis as assessed by x-ray angiography showed localized wall thickness of 4.38+/-0.71 mm (range, 3.30 to 5.73 mm). The difference in maximum wall thickness between the normal subjects and patients was statistically significant (P<0.0001). CONCLUSIONS: In vivo high-spatial-resolution BB-MR provides a unique new method to noninvasively image and assess the morphological features of human coronary arteries. This may allow the identification of atherosclerotic disease before it is symptomatic. Further studies are necessary to identify the different plaque components and to assess lesions in asymptomatic patients and their outcomes.

Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis.

BACKGROUND: Arterial remodeling in response to atherosclerosis may be outward (positive) or inward (negative) and is an important mechanism in the clinical manifestations of atherosclerosis and restenosis after percutaneous coronary interventions. Postmortem and intravascular ultrasound studies of arterial remodeling do not allow serial and noninvasive data to be obtained. In a rabbit model of atherosclerosis, we sought to validate MRI as a new tool for documentation of arterial remodeling. METHODS AND RESULTS: Watanabe heritable hyperlipidemic rabbits underwent serial MRI at baseline and 6 months after aortic balloon denudation. The lumen area had a small but significant (P=0.006) increase, from 4.36+/-0.16 to 4. 89+/-0.12 mm(2). There was a large, significant (P<0.0001) increase in the outer wall area, from 7.96+/-0.19 to 10.46+/-0.19 mm(2). The vessel wall area (a marker of atherosclerotic burden) increased significantly (P<0.0001), from 3.61+/-0.07 to 5.57+/-0.09 mm(2). Thus, the increase in atherosclerotic burden over time was completely accounted for by positive arterial remodeling. The subgroup used for histopathological validation confirmed a significant (P<0.0001) agreement between histopathology and MRI for assessment of all 3 parameters. CONCLUSIONS: MRI can provide serial and noninvasive data about the arterial wall, allowing assessment of arterial remodeling in this rabbit model. Thus, MRI appears to be a useful tool for the investigation of arterial remodeling both in native atherosclerosis and after percutaneous coronary intervention.

Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive magnetic resonance imaging.

BACKGROUND: This study was designed to investigate the effects of lipid-lowering by simvastatin on human atherosclerotic lesions. METHODS AND RESULTS: Eighteen asymptomatic hypercholesterolemic patients with documented aortic and/or carotid atherosclerotic plaques were selected for the study. A total of 35 aortic and 25 carotid artery plaques were detected. Serial black-blood MRI of the aorta and carotid artery of the patients was performed at baseline and 6 and 12 months after lipid-lowering therapy with simvastatin. The effects of the treatment on atherosclerotic lesions were measured as changes in lumen area, vessel wall thickness, and vessel wall area, a surrogate of atherosclerotic burden. Simvastatin induced a significant (P<0.01) reduction in total and LDL cholesterol levels at 6 weeks that was maintained thereafter. At 6 months, no changes in lumen area, vessel wall thickness, or vessel wall area were observed. However, at 12 months, significant reductions in vessel wall thickness and vessel wall area, without changes in lumen area, were observed in both aortic and carotid arteries (P<0.001). CONCLUSIONS: This in vivo human study demonstrates that effective and maintained lipid-lowering therapy by simvastatin is associated with a significant regression of atherosclerotic lesions. Our observation suggests that statins induce vascular remodeling, as manifested by reduced atherosclerotic burden without changes in the lumen.

Atherosclerotic aortic component quantification by noninvasive magnetic resonance imaging: an in vivo study in rabbits.

OBJECTIVES: We sought to demonstrate the ability that noninvasive in vivo magnetic resonance imaging (MRI) has to quantify the different components within atherosclerotic plaque. BACKGROUND: Atherosclerotic plaque composition plays a critical role in both lesion stability and subsequent thrombogenicity. Noninvasive MRI is a promising tool for the characterization of plaque composition. METHOD: Thoracic and abdominal aortic atherosclerotic lesions were induced in rabbits (n = 5). Nine months later, MRI was performed in a 1.5T system. Fast spin-echo sequences (proton density-weighted and T2-weighted [T2W] images) were obtained (in-plane resolution: 350 x 350 microns, slice thickness: 3 mm). Magnetic resonance images were correlated with matched histopathological sections (n = 108). RESULTS: A significant correlation (p < 0.001) was observed for mean wall thickness and vessel wall area between MRI and histopathology (r = 0.87 and r = 0.85, respectively). The correlation was also present on subanalysis of the thoracic and upper part of the abdominal aorta, susceptible to respiratory motion artifacts. There was a significant correlation for plaque composition (p < 0.05) between MRI and histopathology for the analysis of lipidic (low signal on T2W, r = 0.81) and fibrous (high signal on T2W, r = 0.86) areas with Oil Red O staining. T2-weighted images showed greater contrast than proton density-weighted between these different components of the plaques as assessed by signal intensity ratio analysis with the mean difference in signal ratios of 0.47 (S.E. 0.012, adjusted for clustering of observations within lesions) being significantly different from 0 (t1 = 39.1, p = 0.016). CONCLUSIONS: In vivo noninvasive high resolution MRI accurately quantifies fibrotic and lipidic components of atherosclerosis in this model. This may permit the serial analysis of therapeutic strategies on atherosclerotic plaque stabilization.

Acute antithrombotic effect of a front-loaded regimen of clopidogrel in patients with atherosclerosis on aspirin.

There is a need for a rapid antithrombotic effect after the administration of antiplatelet drugs in the setting of acute coronary syndromes and percutaneous interventions. Clopidogrel, a new thienopyridine derivative, is an efficient antiplatelet agent. However, the standard regimen of clopidogrel (75 mg/d) requires 2 to 3 days before significant antithrombotic effects. Patients with stable arterial disease on chronic aspirin therapy (n=20) were treated with clopidogrel either with a front-loaded regimen, 300 mg the first day and 75 mg/d the next 7 days, or with a standard regimen, 75 mg/d for 8 days. Blood thrombogenicity was assessed by quantification of platelet-thrombus formation in an ex vivo perfusion chamber, by ADP-induced platelet aggregation, and by ADP-induced fibrinogen binding. At 2 hours, mean total thrombus area with the standard regimen was not significantly reduced. In contrast, at 2 hours, the mean total thrombus area with the front-loaded regimen was significantly decreased by 23.1+/-8.5% versus baseline (P<0.05). ADP-induced platelet aggregation (with 5 and 10 micromol/L) was also significantly (P<0.05) reduced with the front-loaded regimen at 2 hours, with the mean platelet aggregation being 82.2+/-4.4% and 81.8+/-4.5%, respectively, versus baseline. Similarly, flow cytometry demonstrated a significant decrease (P<0. 05) in the ADP-induced fibrinogen binding (with 0.12 and 0.6 micromol/L) at 2 hours in this front-loaded regimen group (36.1+/-2. 0% and 53.2+/-9.3%). With the standard regimen, platelet activity was not significantly reduced at 2 hours. Our data suggest that a front-loaded regimen of clopidogrel added to aspirin achieves a significant antithrombotic effect at 2 hours in patients with known atherosclerotic disease on chronic aspirin therapy. This provides a rationale for using front-loaded clopidogrel in combination with aspirin in percutaneous coronary interventions.

[The best of thrombosis in 2004]. / L'essentiel de 2004 en thrombose.

The optimal pharmacological antithrombotic treatment for interventional coronary procedures is a controversial subject. The ISAR-REACT trial investigated the necessity of a IIb/IIIa glycoprotein inhibitor in procedures not considered at high risk, that is to say excluding acute coronary syndromes, and concluded that there was no additional gain with this treatment compared with placebo when the patient was pre-treated with 600 mg of clopidogrel. The REPLACE-2 trial proposed an alternative to a treatment with NFH and IIb/IIIa glycoprotein inhibitor with the use of a direct antithrombin, bivalirudine. Heparin therapy of acute coronary syndromes and the eventual ensuing interventional coronary procedure may employ NFH or LMWH. New large scale trials (SYNERGY and phase A of the so-called A to Z trial) compared the two approaches and are reported later on. If facilitated angioplasty is a seductive concept, the best antithrombotic association remains to be determined (BRAVE trial). Bitherapy with a platelet inhibitor and an antithrombotic, ximegalatran, was tested in the ESTEEM trial and in the post-infarct period. Bitherapy with platelet inhibitors clopidogrel and aspirin versus clopidogrel alone was tested in patients with "ischaemic" stroke but does not seem to be more effective than monotherapy. In pulmonary embolism, the fondaparinux seems to be an alternative to NFH. Finally, the concept of resistance to platelet inhibitors is in vogue and is the subject of some interesting trials.

Antistreptokinase platelet-activating antibodies are common and heterogeneous.

BACKGROUND: Platelet activation by antistreptokinase (SK) antibodies could impair the clinical effect of SK administration. OBJECTIVE: To better describe anti-SK antibodies with particular emphasis on procoagulant activities as a result of platelet activation. PATIENTS AND METHODS: Sera were collected from 146 patients with coronary artery disease: non-SK-treated, 95 from mainland France, 31 from French Polynesia; 20 patients from mainland in year 2 after SK treatment. Serum-induced SK-dependent platelet activation resulting in procoagulant activities was assessed with washed platelets from five donors representative of the known patterns of reactivities to IgG. RESULTS: Concentrations (2-5252 microg mL(-1)) and fibrinolytic neutralization titres (< 10 to > 1280) were found in the expected wide range and correlated (rho = 0.66, P < 0.0001). Platelet activation was detected with 145 samples, but varied in intensity and pattern (depending on the donors), although there was no systematic hierarchy; it was presumably due to IgG (inhibited by an IgG Fc receptor-blocking antibody and recovered in the IgG fraction) and only partially affected by aspirin. Marked platelet activation could be detected in samples with concentration as low as 2 microg mL(-1), and/or no detectable neutralizing titers. The way of immunization to SK was not found to influence the functional profile of antibodies. CONCLUSION: Anti-SK platelet-activating antibodies are widespread, heterogeneous, poorly predictable on the basis of their antifibrinolytic effect and strong enough to trigger procoagulant activities. Their clinical relevance should be formally assessed, using patients' own platelets for detection owing to the variation of platelet reactivity.

The role of plaque rupture and thrombosis in coronary artery disease.

Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in the industrialized world. The progression of atherosclerotic plaques in the coronary circulation is dependent on several risk factors. It is now clear that plaque composition is a major determinant of the risk of subsequent plaque rupture and superimposed thrombosis. The vulnerability of plaques to rupture is further determined by extrinsic triggering factors. Following rupture, the fatty core of the plaque and its high content of tissue factor provide a powerful substrate for the activation of the coagulation cascade. Plaque rupture can be clinically silent or cause symptoms of ischaemia depending on thrombus burden and the degree of vessel occlusion. In addition, plaque rupture and subsequent healing is recognized to be a major cause of further rapid plaque progression. This review looks at the mechanisms underlying the development and progression of atherosclerotic plaques, factors leading to plaque rupture and subsequent thrombosis and their clinical consequences. Finally, we speculate on targets for future research.

High resolution ex vivo magnetic resonance imaging of in situ coronary and aortic atherosclerotic plaque in a porcine model.

Atherosclerotic plaque composition is central to the pathogenesis of plaque disruption and acute thrombosis. Thus, there is a need for accurate imaging and characterization of atherosclerotic lesions. Even though there is no ideal animal model of atherosclerosis, the porcine model is considered to most closely resemble human atherosclerosis. We report the feasibility of MR imaging and characterizing of atherosclerotic lesions from in situ coronary arteries and aortas in an ex vivo setting and validate this with histopathology. Coronary and aortic atherosclerosis was induced in Yucatan mini-swine (n=4) by a combination of atherogenic diet (6 months) and balloon injury. All coronary arteries were imaged ex vivo on the intact heart, preserving the curvature of their course. The aorta also underwent MR imaging. The MR images were correlated with the matched histopathology sections for both the coronary arteries (n=54) and the aortas (n=43). MR imaging accurately characterized complex atherosclerotic lesions, including calcified, lipid rich, fibrocellular and hemorrhagic regions. Mean wall thickness for the coronary arteries (r=0.94, slope: 0.81) and aortas (r=0.94, slope: 0.81) as well as aortic plaque area (r=0.97, slope: 0.90) was accurately determined by MR imaging (P<0.0001). Coronary artery MR imaging is not limited by the curvature of the coronary arteries in the heart. MR imaging accurately quantifies and characterizes coronary and aortic atherosclerotic lesions, including the vessel wall, in this experimental porcine model of complex atherosclerosis. This model may be useful for future study of MR imaging of atherosclerosis in vivo.

Ventricular dilation after anterior ST-elevation myocardial infarction in the thrombolytic era.

BACKGROUND: The aim of this work was to study changes in end-diastolic volume 6 months after Q-wave and non-Q-wave anterior ST-elevation myocardial infarction by echocardiography. Ventricular dilation after anterior Q-wave myocardial infarction is well-recognized. However, there is a dearth of information about the natural history of ventricular volumes after non-Q-wave myocardial infarction. METHODS: One hundred ninety patients receiving thrombolytic therapy after anterior ST-elevation myocardial infarction were studied. All patients had 2D echocardiograms and 12-lead electrocardiograms recorded within 24 hours of symptoms and at 3, 42, and 180 days later. In addition, a further electrocardiogram was recorded on day 7 to assess patients for the presence of Q waves. Peak creatine kinase over the first 3 days of admission was recorded. End-diastolic volume index was the study end point. RESULTS: Peak creatine kinase was strongly associated with ventricular dilation in both groups (P <.001). Mean end-diastolic volume in the Q-wave group increased significantly from day 1 to 6 months (P <.05) but did not alter after non-Q-wave infarction. However, when patients were selected on predefined criteria for significant change in ventricular dilation (>10 mL/m(2)), then 35% of those with and 15% of those without Q waves fell into this category. Within this group, the increase in end-diastolic volume followed a similar pattern, with the maximum percentage increase occurring between day 1 and 6 weeks. CONCLUSIONS: In the postthrombolytic group of anterior ST-elevation myocardial infarction, a minority of patients without Q-wave development also undergo significant ventricular dilation.

Comparative effects of recombinant staphylokinase and streptokinase on platelet aggregation.

Recombinant staphylokinase (RSTA) has been shown to offer promise as a thrombolytic agent. In contrast to streptokinase (SK), few studies have been devoted to possible effects of RSTA on platelets. We have compared the capacity of RSTA and SK to trigger platelet aggregation and to modify ADP (2.5 microM) response in platelet-rich plasma (PRP) of 125 healthy subjects. Thus, exposure of PRP to SK (40 to 50 micrograms/ml) induced platelet aggregation in 6 out of 25 subjects. However, under the same conditions, RSTA failed to induce platelet aggregation in all cases (25 out of 25 subjects). In contrast to RSTA, SK (0.4 to 50 micrograms/ml) greatly reduced ADP-induced platelet aggregation in 12 out of 25 subjects. Preincubation of plasma with SK is associated with a decrease in the fibrinogen concentration. Furthermore, there was a good correlation between SK-induced fibrinogenolysis and SK-induced platelet aggregation defect (r2 = 0.9; p = 0.001). No fibrinogenolysis was observed when different amounts of RSTA (0.4 to 50 micrograms/ml) were incubated in plasma for one min. However, there was a marked decrease in fibrinogen level (about 50%) when the plasma was incubated for five min with a very high concentration of RSTA. SK markedly enhanced the platelet response to ADP in 13 out of 25 subjects. In PRP of 6 out of 25 subjects, SK induces platelet aggregation and potentiates platelet response to ADP, however in PRP of 7 out of 25 subjects, SK caused only the increase of platelet response to ADP. The monoclonal antibody anti-Fc gamma RIIa1, I-3 (2 micrograms/ml), abolished SK-induced platelet aggregation and SK-enhanced ADP-induced platelet aggregation. In all cases (25 out of 25 subjects), RSTA failed to potentiate platelet response to ADP. These findings confirm that RSTA has a lesser fibrinogenolytic ability than SK and suggest its negligible effect on platelet function.

Human anti-streptokinase antibodies induce platelet aggregation in an Fc receptor (CD32) dependent manner.

Exposure to streptokinase (SK) elicits anti-SK antibodies (Abs), which inhibit fibrinolysis and induce platelet aggregation. The mechanism of the latter is not fully understood, although it seems to involve platelet binding by a plasminogen streptokinase and anti-SK ternary complex. Anti-SK Abs were purified by affinity chromatography from serum of patients having received SK for acute myocardial infarction (AMI), and were shown to be of the IgG type. Their effects were studied with (i) human platelets in citrated plasma in the presence of SK or acetylated plasminogen-SK activator complex (APSAC), and (ii) in washed platelets, resuspended in Tyrode buffer after lowering the ionic strength, in the presence of APSAC (which provides both SK and plasminogen). An antibody concentration-response curve was obtained, showing a plateau in the presence of 0.1 mg/ml IgG. By increasing the concentration of APSAC, we obtained a unimodal response curve, the optimal concentration of APSAC being 0.05 U/ml. Aggregation was suppressed by chelating calcium with EDTA, blocking fibrinogen binding by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), and raising intraplatelet cAMP with Iloprost (a prostacyclin analogue). Aggregation required the interaction of the anti-SK Ab Fc domain with the platelet Fc-gamma receptor type II, also known as CD32, since: (i) it was blocked by the monoclonal antibody IV-3 directed against CD32, (ii) it did not occur with F(ab)'2 fragments, which block the response to the intact IgG. The clinical relevance of these platelet-activating anti-SK antibodies remains to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Late coronary angioplasty and ventricular late potentials.

To assess the effect of successful late coronary angioplasty of an occluded infarct-related artery on the prevalence of ventricular late potentials, signal-averaged electrocardiograms were recorded in 123 consecutive patients surviving a first acute myocardial infarction (58 with and 65 without mechanical reperfusion of the occluded coronary artery). Multivariate analysis showed that successful reperfusion by late angioplasty of the infarct artery contributes to a decrease in the prevalence of late potentials.