Abstract-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-g/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. (Arterioscler Thromb Vasc Biol.

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.

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.