Catherine Jais

Fibrinolysis of mechanical prosthetic valve thrombosis: a single-center study of 127 cases.

OBJECTIVES This study was designed to analyze the results of fibrinolytic treatment (FT) in a large single-center group of patients with prosthetic heart valve thrombosis (PHVT). BACKGROUND Fibrinolytic treatment of PHVT represents an alternative to surgery, but is still controversial because of the risk of embolism. METHODS A total of 110 consecutive patients presenting with 127 instances of PHVT received FT between 1978 and 2001. The diagnosis of PHVT was established mainly by fluoroscopy and/or echocardiography. The first fibrinolytic agent used was streptokinase (SK) in 49 cases, urokinase (UK) in 41 cases, and recombinant tissue-type plasminogen activator (rtPA) in 37 cases. A second FT was consecutively infused in 38 patients (30%) and a third FT in 11 others. The efficacy of FT was assessed from hemodynamic parameters derived from echographic examinations as well as on clinical grounds. RESULTS Complete resolution of hemodynamic abnormalities was seen in 90/127 patients, partial resolution in 22/127 patients, and no change in 15/127 patients after one or more consecutive fibrinolytic regimens. When SK or rtPA were used as the first fibrinolytic agent, they appeared significantly superior to UK in terms of valve reopening. Fifteen patients died. Severe hemorrhagic complications were observed in six patients. Nineteen documented embolic events occurred during FT. Finally, PHVT recurred in 24 patients, 17 of whom were retreated with lytic agents. CONCLUSIONS These results indicate that FT is effective in most cases of PHVT, regardless of prosthesis or site involved. However, embolism, hemorrhage, and death were not uncommon after lytic therapy of left-sided PHVT, limiting its application to patients at high risk with alternative treatment.

VerifyNow and VASP phosphorylation assays give similar results for patients receiving clopidogrel, but they do not always correlate with platelet aggregation

Point-of-care testing permits an evaluation of the efficacy of drugs used in the treatment of acute coronary syndromes (ACS). An increased risk of thrombosis after coronary stenting for ACS patients treated with aspirin and clopidogrel has been linked to high platelet reactivity and, for certain patients, poor drug response. The objective of our study was to compare the VerifyNow-P2Y12 device with the VASP (vasodilator-stimulated phosphoprotein) phosphorylation assay and ADP-induced platelet aggregation as assessed by light transmission aggregometry in a group of 81 ACS patients (100 tests) treated in our hospital. There was a good correlation between VerifyNow-P2Y12 and VASP especially during the chronic phase of one month or more after the ischemic event, whereas discordance was sometimes seen with platelet aggregometry. The rapidity and ease of use of the VerifyNow device suggests that it has a valuable place in point-of-care testing of ACS patients.

Delayed immunologic thrombocytopenia induced by abciximab

Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.

Thrombocytopenia after abciximab use results from different mechanisms.

Our study concerns thrombocytopenia in patients with acute ischaemic coronary artery disease receiving anti-platelet drugs to the aIIbb3 integrin (GPIIb/IIIa). We have screened for drug-dependent antibodies (DDAB) in 18 patients who suffered a fall of > 50% in platelet count (9 patients had a nadir of <50,000 platelets/microl) after receiving abciximab and related results to clinical outcome. Serum or plasma was screened for DDAB using (i) a direct ELISA against purified aIIbb3, aIIbb3-abciximab complexes or abciximab alone, (ii) control platelets and flow cytometry and (iii) monoclonal antibody immobilisation of platelet antigens. DDAB were found for 11 patients, with aIIbb3 ELISA the most sensitive test. Progressive platelet consumption linked with haemoglobin loss and/or use of intra-aortic balloon pumping, another potential cause of a fall in platelet count, was also evaluated. DDAB were identified that recognised aIIbb3 associated with abciximab and/or abciximab alone. Screening of both progressive and delayed thrombocytopenia (appearing after 5 to 11 days) suggested that antibodies against abciximab preceded those recognising neo-epitopes on aIIbb3, with a time-dependent broadening of antibody specificities. Higher titres were seen after second abciximab use. Five antibodies were platelet-activating. In conclusion, the mechanisms responsible for this complication of anti-aIIbb3 therapy are multiple and often associated with a complex immune response.

Prehospital administration of enoxaparin before primary angioplasty for ST-elevation acute myocardial infarction

We hypothesized that primary percutaneous coronary intervention (PCI) could be performed with prehospital injections of enoxaparin for ST segment elevation myocardial infarction (STEMI). Enoxaparin has been studied in combination with fibrinolysis in STEMI, but has not been evaluated as anticoagulant regimen for primary PCI. In a prospective registry, 143 consecutive patients with STEMI received prehospital 0.5 mg/kg intravenous (IV) bolus followed by 1 mg/kg subcutaneous enoxaparin before immediate transport for PCI. We focused on anti‐Xa activities before and after PCI, bleedings, infarct‐related artery patency, and major adverse cardiac events at day 30. Anti‐Xa activity was at the target level (>0.5 IU/ml) in 99% of patients during PCI, and in 100% 4 hr after injections; over‐anticoagulation (>1.5 IU/ml) was noted in 9 and 2%, respectively at start and 4 hr after injections. Bleeding complications with enoxaparin were rare : major in 1.4% (no intracranial hemorrhages), minor in 2.1%. A patent infarct‐related artery (TIMI 2 + 3) was observed in 40.6% of the patients before PCI. TIMI 3 flow was obtained in 88.1% of the cases after PCI. Major adverse cardiac events at 30 days occurred in 5.6 % of cases: death 2.8%, reinfarction 3.5%, and target lesion revascularisation 3.5%. Prehospital IV and subcutaneous enoxaparin provides simple and rapid anticoagulation for PCI in STEMI patients. Enoxaparin dose needs to be reduced regarding the 9% of over‐anticoagulation. This study suggests the potential of enoxaparin as an alternative anticoagulant regimen for primary PCI.

Impact of restenosis after optimal directional coronary atherectomy on regional left ventricular function

To assess the effect of optimal directional coronary atherectomy (DCA) on restenosis and left ventricular (LV) function, 95 patients who underwent DCA and adjunctive balloon angioplasty for de novo lesions were prospectively followed for 6 months. Absolute and relative coronary lumen measurements were analyzed with online quantitative coronary angiography. LV volumes, ejection fraction, and segmental wall motion were measured off-line according to the radial method for LV cineangiograms acquired in a right anterior oblique projection. Target vessels were the left anterior descending artery in 63 patients and right coronary artery in 32. Mean (+/- SD) reference diameter was 3.58 +/- 0.65 mm. Mean lumen diameter improved significantly after DCA from 1.19 +/- 0.44 to 3.03 +/- 0.45 mm, yielding a 14 +/- 10% residual stenosis. Overall angiographic restenosis rate (> 50% stenosis in diameter) at control was 23%. In patients without restenosis, there were no significant changes in LV volumes or in LV pressures. In this subgroup, ejection fraction improved significantly in the left anterior descending group (mean difference 3 +/- 10%, p < 0.04). Moreover, there was an increase in fractional shortening of all anterior segments (mean difference 11 +/- 16%, p < 0.005). Improvement in fractional shortening was less marked in the right coronary artery group even without restenosis. We conclude that: (1) optimal DCA can achieve a low restenosis rate in selected large vessels, (2) long-term beneficial effects on regional LV function are possible, particularly in patients with left anterior descending disease and in the absence of coronary restenosis.

063 A single pre-hospital enoxaparine protocole for all STEMI admitted to ICU: One year experience and one year follow-up in Haut Lévêque cardiological hospital

Background: Clopidogrel and low-dose aspirin have become the mainstay oral antiplatelet regimen to prevent recurrent ischaemic events after acute coronary syndromes or stent placement. The frequent genetic functional variant 681 G>A (*2) of cytochrome P450 2C19 (CYP2C19) is an important contributor to the wide variability between individuals of the antiplatelet effect of clopidogrel. We assessed whether the CYP2C19*2 polymorphism affected long-term prognosis of patients who were chronically treated with clopidogrel.

CV18 Apport de l’IRM cardiaque dans le diagnostic de la cardiomyopathie apicale transitoire ou Tako Tsubo

Objectifs Le syndrome de Tako Tsubo se caracterise par une akinesie apicale et medioventriculaire reversible et l’absence d’atteinte coronaire angiographiquement significative. Le but de ce travail est d’evaluer l’interet diagnostique de l’IRM. Materiels et methodes Depuis mai 2004 une IRM a ete realisee chez 15 femmes (âge = 75 ± 8 ans) remplissant les criteres de syndrome de Tako Tsubo, dans les 24 premieres heures suivant leur admission et a 2 mois. La fonction ventriculaire gauche (VG) etait quantifiee et la perfusion myocardique etudiee aux temps precoce et tardif apres injection de gadolinium. Resultats La fraction d’ejection (FE) lors de l’examen initial etait de 0,48 ± 0,16. Les troubles de la cinetique segmentaire concernaient les segments medioventriculaires et distaux du VG sans topographie attribuable a une lesion coronaire. On ne retrouvait pas d’anomalie de perfusion aux temps precoce et tardif. Au deuxieme mois, la cinetique VG et la perfusion myocardique etaient normales (FE a 0,77 ± 0,05). Conclusion L’absence d’hyposignal precoce en IRM ne plaide pas pour un hypo debit microcirculatoire expliquant les anomalies cinetiques transitoires. L’absence de rehaussement tardif semble permettre d’eliminer un infarctus du myocarde ou une myocardite.