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.

[Is early stent thrombosis an inflammatory disease? A study of 1306 implantations]. / Thromboses precoces de stent: une maladie inflammatoire? A propos de 1306 implantations.

The authors tried to determine the clinical characteristics and predisposing factors of early stent thrombosis (EST) through the study of 15 patients who had had angiographically diagnosed stent thrombosis within 30 days of the implantation of the stent. The cases were compared to 29 control random patients collected between January 1, 2000 and August 31, 2001. Out of the 1306 patients who had been given coronary stents, 20 of them (1.5%) had an OO.. EST, representing 1.3 per patient. The patients, 12 males and 3 females, had a mean age of 62 + 10.3 years ranging between 46 and 77 years. EST occurred within 7.4 + 3.8 days (2 hours n 29 days) on average, in the left anterior descending branch (10 cases), in the right coronary artery (6cases) or in the left circumflex (3 cases) and finally in the postero-lateral branch (1 case). Stent recanalisation was performed within 3.4 + 2 hours (1-7 hours) on average. In spite of prompt revascularization, the problem progressed to MI in all cases and to subsequent death in 3 cases (20%). Procedure related variables of emergency PTCA, dissection, anatomical type B or C coronary lesions, related WBC count and C- reactive protein were significantly associated with EST while remained a rare event following PTCA. The incidence is low but the prognosis is still poor in spite of early intervention. Other studies are needed to confirm the probable inflammatory nature of this complication.

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.

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.

Cardiac magnetic resonance imaging for the diagnosis of patients presenting with chest pain, raised troponin, and unobstructed coronary arteries.

To evaluate the incremental diagnostic and prognostic value of cardiac magnetic resonance (CMR) in patients with chest pain, raised troponin and unobstructed coronary arteries, and to compare subsequent event rates between diagnostic groups. 130 patients (mean age: 54 ± 17) presenting with troponin-positive acute chest pain and unobstructed coronary arteries were included. All patients were managed according to European Society of Cardiology guidelines, including echocardiography, and had CMR within 6.2 ± 5.3 days of presentation. During follow-up, major adverse cardiovascular events (MACE) were recorded. CMR provided a diagnosis in 100 of 130 patients (76.9%), with the remaining 30 (23.1%) having a normal examination. CMR diagnosed 37 (28.5%) acute myocardial infarctions, 34 (26.1%) myocarditis, 28 (21.5%) apical ballooning syndromes and 1 (0.8%) hypertrophic cardiomyopathy. When a single diagnosis was suspected by the referring physician, CMR validated this diagnosis in 32 patients (76.2%). CMR provided a formal diagnosis in 61 patients (69.3%) in which the clinical diagnosis was uncertain between at least two possibilities. CMR corrected a wrong diagnosis in 10 patients (7.7%). CMR-suggested diagnosis led to a modification of therapy in 42 patients (32.3%). Median follow-up was 34 months (interquartile range 24-49) in 124 patients. Sixteen patients (12.9%) experienced MACE. MACE rate was not different between patients with a conclusive CMR and normal CMR. In patients with acute troponin-positive chest pain and unobstructed coronary arteries, early CMR has important diagnostic and therapeutic implications. However its association with occurrence of MACE during mid term follow-up was not obvious.

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.

Comparative analysis of cardiac magnetic resonance viability indexes to predict functional recovery after successful percutaneous coronary intervention in acute myocardial infarction.

The aim of this study was to examine the relative value and the influence of the association of 4 cardiac magnetic resonance (CMR) viability indexes for predicting segmental functional recovery after optimal pharmacologic therapies and early percutaneous coronary intervention in acute myocardial infarction (AMI). CMR has been shown to predict functional recovery after AMI. The relative predictive value of CMR viability indexes remains disputed and has not been described in AMI reperfused within the first 12 hours. Sixty-nine patients with a first reperfused (<12 hours) Thrombolysis In Myocardial Infarction grade 3 AMI (61 men, 57.6 +/- 12.6 years) were studied on day 5 +/- 2. Low-dose (10 microg/kg/min) dobutamine response (DOB), microvascular obstruction (MVO), relative delayed enhancement extent (DE), and transmural DE pattern (TMDE) were assessed in each of the 17 left ventricular segments. Segmental functional outcome was assessed by CMR at 3 months. Logistic regression and Bayesian probabilities evaluated the association between viability indexes and functional segmental outcome. At rest, 27% of segments (314 of 1,173) were dysfunctional of which 53% (165 of 314) recovered at follow-up. Odd ratios for dobutamine response, MVO, DE, and TMDE were 15.8, 5.9, 2.6, and 2.5 respectively. The probability of segmental recovery was 0.84 when dobutamine response was positive and increased successively to 0.91 when adding MVO absence, 0.94 when adding TMDE absence, and 0.97 when adding DE absence. In conclusion, contractile response to low-dose dobutamine is the best predictive factor of segmental recovery after Thrombolysis In Myocardial Infarction grade 3 early reperfused AMI. Its value is further increased by other CMR viability indexes.

Management of prosthetic heart valve obstruction: fibrinolysis versus surgery. Early results and long-term follow-up in a single-centre study of 263 cases.

Optimal management of prosthetic heart valve obstruction (PHVO) remains controversial even though surgery is usually recommended. To better define the efficacy and safety of fibrinolysis versus surgery in the pre- and post-transoesophageal echocardiography (TEE) eras. We analysed initial results and follow-up data from a large, retrospective, single-centre series, comparing fibrinolysis and surgery in patients with PHVO treated over 20 years. Two hundred and sixty-three consecutive episodes of PHVO in 210 patients, mainly left sided, were managed in our institution by either fibrinolysis (n=127) or surgery (n=136). Early clinical evolution was assessed in terms of haemodynamic success and complications. Concerning early results, there were no significant differences between the two groups in terms of mortality (10%). However, haemodynamic success was significantly more frequent in the surgical group (89% versus 70.9% p<0.001), embolic episodes were significantly more frequent in the fibrinolysis group (15% versus 0.7%, p<0.001), as were total complications (25.2% versus 11.1%, p=0.005). Long-term follow-up, with a mean duration of 6 years (range: 0-20), was obtained and showed significantly better results in the surgical group in terms of recurrence (p=0.021) and mortality (p=0.002). In univariate and multivariable analyses, NYHA functional class at presentation was a strong predictor of late death (p<0.01). Management of patients during the pre- and post-TEE eras was significantly different, since introduction of TEE surgery has become the preferred therapeutic strategy. Results of this extensive single-centre experience indicate that since the introduction of TEE, surgery is more frequently performed than fibrinolysis due to the improvement of thromboembolic risk assessment. Furthermore, prompt surgical treatment is associated with a better early success rate and a significantly lower incidence of complications than fibrinolysis in left-sided PHVO. However, fibrinolysis may be justified in selected cases. Long-term follow-up showed significantly better results in the surgical group in terms of recurrence and mortality.

MRI for the diagnosis of left ventricular apical ballooning syndrome (LVABS).

To compare MRI findings of left ventricular apical ballooning syndrome (LVABS) with those of acute myocardial infarction (AMI). Fifteen patients with a LVABS (group 1) and 25 patients with an AMI (group 2) were explored by MRI within 24 h after admission. Comparison of both groups for the number and location of myocardial segments with abnormal wall motion and abnormal perfusion or delayed enhancement was performed. The number of involved segments was higher in group 1 than in group 2 (p<0.001). In group 1, segments with abnormal wall motion were distributed in more than one vascular territory in all patients and confined to the medial, distal, and apical regions of the left ventricle. Subendocardial hypoenhancement was observed in 16/25 patients (64%) in group 2 and in none of group 1 (p<0.001). All patients in group 2 demonstrated delayed-enhancement abnormalities in a vascular distribution, whereas none in group 1 presented this abnormality (p<0.001). Diffusely distributed segmental wall-motion abnormalities and absence of first-pass perfusion hypoenhancement and of delayed enhancement at MRI help to differentiate LVABS from AMI. In the acute phase or in some difficult cases, cardiac MRI should become routine to confirm the diagnosis of LVABS.

Early characterization of atherosclerotic coronary plaques with multidetector computed tomography in patients with acute coronary syndrome: a comparative study with intravascular ultrasound.

We compared 16-slice computed tomography (CT) with intravascular ultrasound (IVUS) in their ability to identify the culprit lesion, and to assess plaque characterization and vascular remodelling in acute coronary syndrome (ACS). Twenty patients were prospectively studied. Coronary plaque identification and characterization were compared using 16-slice CT and 40-MHz catheter-based IVUS. Minimum lumen area (MLA), cross-sectional vessel area (CVA) and vessel remodelling were determined for each comparable lesion. One hundred and sixty-nine segments were compared and 84 plaques analysed. Sixteen-slice CT detected 95% of culprit lesions (19/20). No feature suggestive of plaque rupture was detected by 16-slice CT. Attenuation measurements within all lesions revealed different values for hypoechoic (38 +/- 33 HU), hyperechoic (94 +/- 44 HU), and calcified plaques (561 +/- 216 HU), (P < 0.001). Agreement between 16-slice CT and IVUS on measuring MLA and CVA was evaluated using Bland-Altman analysis. Pearson and intra-class coefficient (ICC) were 0.81 and 0.70 for MLA, and 0.81 and 0.36 for CVA, for 16-slice CT and IVUS, respectively. Agreement between both techniques for vessel positive remodelling was moderate (kappa = 0.54, P < 0.001). Sixteen-slice CT has shown moderate accuracy in quantifying and characterizing coronary plaques compared with IVUS. Spatial resolution of 16-slice CT remains a major limitation, however, to accurately assess the complex lesions involved in ACS.

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 (i.v.) 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 i.v. 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.

Acute occlusion of the left circumflex coronary artery during mitral isthmus linear ablation.

Occlusion of LCX During RF Catheter Ablation. We report a case of acute occlusion of the left circumflex coronary artery during catheter ablation in the coronary sinus to complete the linear lesion between the postero-lateral mitral annulus and the left inferior pulmonary vein for the treatment of atrial fibrillation.