Echocardiographic evaluation and N-terminal pro-brain natriuretic peptide measurement of patients hospitalized for heart failure during weaning from mechanical ventilation.

BACKGROUND: Weaning patients with heart failure who have required mechanical ventilation remains challenging. We evaluated echocardiographic indexes and N-terminal pro-brain natriuretic peptide (NT-proBNP) as markers of acute cardiac dysfunction before and after spontaneous breathing trials (SBT) in such patients to assess their ability to predict subsequent successful extubation. METHODS: Forty-four patients who underwent their first SBT were prospectively included. Plasma levels of NT-proBNP and transthoracic echocardiography indices including cardiac index, E/A ratio and E/Ea ratio were recorded immediately before commencing and just before the end of SBT. RESULTS: Ten patients (22.7%) failed their SBT. No significant difference was observed concerning baseline echocardiographic data and NT-proBNP level between the patients who succeeded the SBT or those that failed. Cardiac index increased significantly at end-SBT in patients who passed (3.3 [3.06-3.77] vs. 3 [2.68-3.3] L/min/m(2), P<0.001), whereas it remained unchanged in those that failed. E/Ea ratio (16.8 [8.5-27.3] vs. 10.7 [6.7-20.5], P=0.006) and NT-proBNP level (8199 [3106-10949] vs. 4200 [1855-7125] pg/mL, P=0.004) increased significantly in those who failed the SBT, in contrast to the weaning success group where they remained unchanged. CONCLUSION: Neither NT-proBNP level nor the studied echocardiographic indices before SBT were able to predict SBT outcome in patients presenting with severe heart failure. Failure to increase the cardiac index and increases in both E/Ea ratio and NT-proBNP levels were seen at end-SBT in patients who failed the SBT, and may reflect failure of myocardial reserve to cope with the stress of SBT.

[Multiple myocardial infarctions: pancoronary destabilization evaluated by cardiac MRI]. / Infarctus du myocarde à localisations multiples: preuve par IRM cardiaque des conséquences de la pancoronarite.

PURPOSE: Complete intravascular ultrasound study examination of all three coronary arteries in patients with first acute coronary syndrome very frequently revealed one or more atherosclerotic plaque ruptures associated with the culprit lesion. The aim of this study was to evaluate using cardiac MRI the incidence of multiple necroses in patients with myocardial infarction. The study sought to detect delayed enhancement in a zone different from the necrosis area concerned by the culprit occlusion. METHODS: Eighty consecutive patients who were referred for a first myocardial infarction underwent angioplasty within the first 12 hours after chest pain beginning. Each patient was examined within four to eight days following the acute phase. Cardiac MRI evaluated left-ventricle function (TrueFISP sequence) and used a T2 weighted short-inversion-time, inversion recovery sequence (STIR) in order to visualize myocardial oedema; delayed enhancement imaging data were then acquired after injection of gadolinium. RESULTS: In eight patients (10%), we observed two delayed enhancement areas associated with wall-motion abnormalities. One was attributed to the culprit occlusion; the second corresponded to a different coronary artery. In five patients, this second zone was related to an old coronary occlusion confirmed by angiography and the STIR sequence. However, in three patients, the second delayed enhancement area corresponded to a coronary artery stenosis with normal flow. CONCLUSION: In patient with acute myocardial infarction, MRI sometimes detects a necrosis area which was not initially suspected. This observation illustrates the consequences of pancoronary destabilization.

[Fibrinolysis and thrombosis of mechanical valvular prosthesis: risk stratification by transesophageal echocardiography]. / Fibrinolyse et thrombose de prothèse valvulaire mécanique: stratification du risque par échocardiographie transoesophagienne.

The place of fibrinolysis in the treatment of mechanical valvular prostheses is still much discussed. The aim of this work is to define the role of transoesophageal echocardiography in risk stratification. This monocentric study draws on 49 cases of thrombolysis preceded by transoesophageal echocardiography (average age 62.1 years, 37 mitral, 11 aortic, 1 tricuspid, 1 mitro-tricuspid). There were 41 obstructive thromboses (OT) and 8 non-obstructive thromboses (NOT). Clinical events and the effectiveness of fibrinolysis were studied as a function of the obstructive or non-obstructive character of the thrombosis and the size of the thrombus < 10 mm (n = 33) or > or = 10 mm (n = 16). Complete success was observed in 34 patients (69.4%). Follow up revealed 2 early cerebral haemorrhages (4.1%) of which one was in the NOT group, and six systemic emboli (12.2%) of which one was in the NOT group. There was a relationship between the size of the thrombus and embolus at the limit of significance in favour of an increased risk of embolus for a voluminous thrombus. Furthermore, the mobility of the thrombi went in hand with an increased rate of systemic emboli (p < 0.01). The rate of failure of fibrinolysis and/or complications correlated with the size of thrombus (complete success in 88% of the < 10 mm thrombus group, versus 35% in the > or = 10 mm; p < 0.01). This work underlines the significance of trans-oesophageal echocardiography in the therapeutic choice for valvular prosthesis thrombosis and suggests that the existence of a voluminous thrombus especially if mobile is a contra-indication for fibrinolysis.

[Hematoma of the aortic wall: from diagnosis to treatment]. / Hématome de la paroi aortique: du diagnostic au traitement.

Haematoma of the thoracic aortic wall is a relatively new concept, the physiopathology of which remains controversial. It results from an haemorrhage of the aortic wall due to rupture of the vasa-vasorum without communication with the arterial lumen. This is a diagnosis of elimination of dissection of the aorta which has been made possible by modern techniques of imaging, such as transoesophageal echocardiography, helicoidal scanner and magnetic nuclear resonance imaging. The prognosis of haematoma of the aortic wall is not as bad as that of dissection of the aorta. Recent studies have shown that the condition may stabilise, regress or progress towards complications of two types: early, dissection or fissuration of the aorta, and late, aortic aneurysm. This is a medico-surgical emergency, the treatment of which is not well codified. However, schematically, haematoma of the aortic wall should be managed in the same way as dissection of the aorta: surgery when the ascending aorta is affected, medical treatment in other cases in the absence of complications.

Accessibility of abciximab to megakaryocytes and endothelial cells in the bone marrow compartment: studies on a patient receiving antithrombotic therapy.

Abciximab, chimaeric Fab fragments of the monoclonal antibody 7E3 (c7E3 Fab), has achieved widespread use as an anti-platelet agent for blocking GP IIb-IIIa (alphaIIbbeta3) function and preventing ischaemic complications after coronary artery angioplasty. However, its accessibility to the bone marrow compartment during therapy is unknown, as is its ability to bind alphavbeta3 in vivo. Using electron microscopy and immunogold labelling, we have looked for abciximab in the bone marrow of a patient who became thrombocytopenic during treatment. The presence of abciximab was assessed on ultrathin frozen sections of a marrow aspirate, the drug being revealed by a rabbit antibody to c7E3 Fab. Labelling was maximal on fragmenting megakaryocytes (MK) and proplatelets in the vascular sinus and in direct access to the blood compartment. Not only the plasma membrane but also the demarcation membrane system (DMS) and the membranes of alpha-granules were labelled. Abciximab was also revealed on the luminal surface of endothelial cells lining the marrow sinuses, thereby confirming for the first time its ability to bind to alphavbeta3 in vivo. The study revealed no signs that abciximab had accumulated in the marrow.

Expression of markers of platelet activation and the interpatient variation in response to abciximab.

Our study concerns the biological effects of abciximab (c7E3 Fab, ReoPro), a powerful new antiplatelet drug that blocks glycoprotein (GP) IIb-IIIa complexes. Samples were examined from 6 patients with coronary artery disease who received a bolus of abciximab followed by a 10- microg/min infusion for at least 18 hours before percutaneous transluminal coronary angioplasty. Inhibition of ADP-induced PA was maximal for 4 patients but partial (79% and 53%) for 2 others during the infusion. Flow cytometry performed with monoclonal antibodies (PAC-1, AP-6, and F26) specific for the "activated" GP IIb-IIIa complex revealed large decreases in the expression of activation markers on platelets during therapy, but these decreases were less marked when inhibition of ADP-induced PA was incomplete. Residual aggregation was seen for all patients during the infusion when TRAP 14-mer peptide or thrombin was the stimulus. Unblocked GP IIb-IIIa complexes were detected on thrombin-stimulated platelets from the patients by immunoelectron microscopy performed using the monoclonal antibody AP-2. Unblocked GP IIb-IIIa complexes were also detected by flow cytometry when platelets preincubated for 1 hour in vitro with abciximab under saturating conditions were (1) incubated with TRAP 14-mer or (2) permeabilized with Triton X-100. In confirming interpatient variation in the platelet response to a standard dose of abciximab, our results also show that an uninhibited internal pool of GP IIb-IIIa complexes may mediate a residual response to strong agonists.

Labeling of the internal pool of GP IIb-IIIa in platelets by c7E3 Fab fragments (abciximab): flow and endocytic mechanisms contribute to the transport.

Abciximab is a new antiplatelet therapeutic in ischemic cardiovascular disease. The drug, chimeric Fab fragments of a murine monoclonal antibody (MoAb) (c7E3), blocks GP IIb-IIIa function. However, its capacity to reach all receptor pools in platelets is unknown. Electron microscopy and immunogold labeling were used to localize abciximab in platelets of patients receiving the drug for up to 24 hours. Studies on frozen-thin sections showed that c7E3 Fab, in addition to the surface pool, also labeled the surface-connected canalicular system (SCCS) and alpha-granules. Analysis of gold particle distribution showed that intraplatelet labeling was not accumulative and in equilibrium with the surface pool. After short-term incubations of platelets with c7E3 Fab in vitro, gold particles were often seen in lines within thin elements of the SCCS, some of which appeared in contact with alpha-granules. Little labeling was associated with Glanzmann's thrombasthenia platelets, confirming that the channels contained bound and not free c7E3 Fab. Endocytosis of abciximab in clathrin-containing vesicles was visualized by double staining and constitutes an alternative mechanism of transport. The remaining free pool of GP IIb-IIIa was evaluated with the MoAb AP-2; flow cytometry showed it to be about 9% on the surface of nonstimulated platelets but 33% on thrombin-activated platelets. The ability of drugs to block all pools of GP IIb-IIIa and then to be associated with secretion-dependent residual aggregation must be considered when evaluating their efficiency in a clinical context.

[Contrast echocardiography and myocardial perfusion: what is the current status?]. / Echocardiographie de contraste et perfusion myocardique: où en sommes-nous?

Progress in the field of echocardiographic contrast agent combined with progress in imaging techniques (second harmonic imaging, intermittent imaging, Doppler Energy) should allow a real revolution in the field of noninvasive cardiac imaging, and one of the main advantages will probably be myocardial perfusion imaging in ischaemic heart disease.

[Role of echocardiography in the diagnosis of acquired diseases of the thoracic aorta]. / Place de l'échocardiographie dans le diagnostic des maladies acquises de l'aorte thoracique.

The diagnosis and follow-up of acquired thoracic aortic disease have greatly improved with advances in transthoracic and transoesophageal echocardiographic techniques. In emergency situations, transoesophageal echocardiography is the key diagnostic investigation for dissection, significantly speeding up surgical referral. Atherosclerosis of the aorta is the second clinical situation in which transoesophageal echocardiography confirms its superiority over other imaging techniques for the recognition of intra-aortic debris carrying a high embolic risk.

PAICA: a method for characterizing platelet-associated antibodies--its application to the study of idiopathic thrombocytopenic purpura and to the detection of platelet-bound c7E3.

In idiopathic thrombocytopenic purpura (ITP), autoantibodies reacting with antigens on the platelet membrane bring about accelerated platelet destruction. We now report PAICA ("Platelet-Associated IgG Characterization Assay"), a method for detecting autoantibodies bound to specific membrane glycoproteins in total platelet lysates. This monoclonal antibody (MAb) capture assay takes into account the fact that antibodies on circulating platelets may be translocated to internal pools as well as being on the surface. A total of twenty ITP patients were examined by PAICA, and the results compared with those obtained by measuring (i) serum antibodies bound to paraformaldehyde-fixed control platelets by ELISA, (ii) IgG bound to the surface of the patient's own platelets by flow cytometry (PSIgG), (iii) total platelet-associated IgG (PAIgG) by ELISA and (iv) serum antibodies reacting with control platelets by MAIPA ("Monoclonal Antibody-specific Immobilization of Platelet Antigens"). Of twelve patients with elevated PAIgG, nine had increased PSIgG yet eleven reacted positively in PAICA. Of these, eight possessed antibodies directed against GP IIb-IIIa, two against GP Ib-IX and one patient possessed antibodies directed against GP IIb-IIIa and GP Ia-IIa respectively. Only seven of the patients possessed serum antibodies detectable by MAIPA. PAICA was also able to detect platelet-associated c7E3 (the chimeric form of Fab fragments of the MAb 7E3) following its infusion during antithrombotic therapy, when it proved more sensitive over a seven-day period than a MAIPA assay adapted for assessing surface-bound antibody. We propose that PAICA provides added sensitivity to the detection of platelet-associated antibodies in immune thrombocytopenias or following therapy with humanized MAbs.

[A study of platelet activation following coronary angioplasty. Effect on acute occlusion and restenosis]. / Etude de l'activation plaquettaire après angioplastie coronaire. Influence sur l'occlusion aiguë et la resténose.

The development of monoclonal anti-platelet antibodies to activation-dependent epitopes has made possible the study of the appearance of activated platelets in the blood by cytometry. This was undertaken in 35 patients undergoing coronary angioplasty. Blood was sampled through the femoral venous catheter introducer before the procedure, at 3 minutes and 3, 24 and 48 hours after angioplasty. Systematic coronary angiography was performed at about 6 months and vessel diameters were quantified by a digitised technique. In general, platelet activation was not observed before angioplasty or in the first hours following the procedure. On the other hand, a significant number of activated platelets was observed secondarily : 7 +/- 7.3% at the 24th hour and 6.8 +/- 5.9% at the 48th hour. There was a significant correlation between the level of platelet activation before angioplasty and that at the 24th hour (r = 0.52, p = 0.01). There was a tendency to more activated circulating platelets before and 24 hours after angioplasty in patients with acute occlusion. The correlation coefficient between the level of activated platelets 24 hours after angioplasty and progression of stenosis at 6 months was not statistically significant (r = 0.29). Therefore, the authors demonstrated platelet activation, which was sometimes considerable, inconstantly in circulating venous blood of patients with angina 24 hours after coronary angioplasty despite treatment with aspirin. Activated platelets may play a role in constituting acute occlusion by thrombosis but their detection was not predictive of restenosis.

Flow cytometry reveals activated GP IIb-IIIa complexes on platelets from patients undergoing thrombolytic therapy after acute myocardial infarction.

We report the detection of activated GP IIb-IIIa complexes on platelets of patients undergoing thrombolytic therapy after acute myocardial infarction. Protocols were established for the monoclonal antibodies (mAbs): VH10, anti-P-selectin, a marker of platelet secretion; 9F9 and F26, two anti-RIBS (receptor-induced binding sites) mAbs specific for fibrinogen (Fg) bound to the GP IIb-IIIa receptor. Of ten patients studied: two were treated with streptokinase, four with APSAC (anisoylated plasminogen-streptokinase activator complex), and three with rt-PA. Platelets were tested on at least five occasions in the week following therapy. The percentage of platelets positive with 9F9 was often high, and reached a maximum within three days. By this time, plasma Fg levels, which fell during fibrinolysis, had begun to return to normal. Levels of activated platelets had fallen to baseline after 7 days. PAC-1, a mAb which binds directly to the activated GP IIb-IIIa complex, confirmed the results with 9F9, but F26 was a less sensitive probe. Binding of the anti-P-selectin mAb (VH10) was low, showing that little secretion had occurred. A concentration-dependent inhibition of 9F9 binding by RGDW peptide, a competitive inhibitor for Fg on GP IIb-IIIa, confirmed that Fg (or epitope-containing degradation products) were being located by the antibody. The activation of GP IIb-IIIa occurred despite the patients receiving aspirin and heparin. Thus platelets of some fibrinolytic patients have an increased tendency for surface activation within the first 72 h after treatment, a finding which would be compatible with an increased thrombotic tendency.

[Continuous monitoring of cardiac output by analysis of the pulse contour]. / Surveillance continue du débit cardiaque par analyse du contour de l'onde de pouls.

One method of continuous cardiac output monitoring by analysis of the radial pulse contour (Qcp) relates left ventricular stroke volume and systolic blood pressure by calculating the impedence characteristic of the aorta (Zao). It was assessed during haemodynamic monitoring by comparing it with the thermodilation method in the pulmonary artery (Qtd) in 20 patients with cardiac failure due to dilated cardiomyopathy (6 cases) and ischaemic cardiomyopathy (14 cases) treated by inotropic agents or vasodilators. Over an average monitoring period of 35 hours 159 measurements of cardiac output were performed by the two methods. There was an excellent correlation between the two methods (r = 0.90; p < 0.001; Qcp = 0.97 Qtd). The systematic error (bias) between the two methods was about 2.5%. The accuracy of Qcp compared with Qtd was 12.5%. During infusion with a vasoactive agent (Piroximone), the method based on pulse contour analysis did not reflect sudden variations in cardiac output. The systematic error between the two methods rose to 19% of the value measured, reflecting the lack of adaptation of parameters of correction in this situation and which necessitated recalibration of Zao at least once after injection of the drug.