Prehospital abciximab in ST-segment elevation myocardial infarction: results of the randomized, double-blind MISTRAL study.

BACKGROUND: The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue. We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) improves ST-segment elevation resolution (STR) after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) is a prospective, randomized, double-blind study. Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). The primary end point was complete (>70%) STR after PCI. Complete STR was not significantly different between the 2 groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow rates before PCI tended to be higher in the ambulance group (46.8% versus 35%, P=0.08) but not after PCI (70.3% versus 65.8%, P=0.49). Slow flow tended to be lower (5.6% versus 13.4%, P=0.07), and distal embolization occurred significantly less often in the ambulance group (8.1% versus 21.1%, P=0.008). One- and 6-month major adverse cardiac event rates were low and similar in both groups. CONCLUSIONS: Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI. However, it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure. Larger studies are needed to confirm these results.

Impact of P2Y12 inhibition by clopidogrel on cardiovascular mortality in unselected patients treated by percutaneous coronary angioplasty: a prospective registry.

OBJECTIVES: The aim of this study was to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by Vasodilator-stimulated phosphoprotein flow cytometry test (VASP- FCT) predicts cardiovascular events in a high-risk population undergoing percutaneous coronary intervention (PCI). BACKGROUND: Impaired platelet responsiveness to clopidogrel is thought to be a determinant of cardiovascular events after PCI. The platelet VASP-FCT is a new assay specific to the P2Y(12) adenosine diphosphate receptor-pathway. In this test, platelet activation is expressed as platelet reactivity index (PRI). METHODS: Four-hundred sixty-one unselected patients undergoing urgent (n = 346) or planned (n = 115) PCI were prospectively enrolled. Patients were classified as low-response (LR) and response (R) to clopidogrel, depending on their PRI. Optimal PRI cutoff was determined by receiver-operator characteristic curve analysis to 61% (LR: PRI > or =61% and R: PRI <61%). Follow-up was obtained at a mean of 9 +/- 2 months in 453 patients (98.3%). RESULTS: At follow-up, total cardiac mortality rates and possible and total stent thrombosis were higher in LR patients. Multivariate analysis identified creatinine clearance (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.93 to 0.98, p < 0.001), drug-eluting stent (HR: 5.73; 95% CI: 1.40 to 23.43, p = 0.015), C-reactive protein (HR: 1.01; 95% CI: 1.001 to 1.019, p = 0.024), and LR to clopidogrel (HR: 4.00; 95% CI: 1.08 to 14.80, p = 0.037) as independent predictors of cardiac death. The deleterious impact of LR to clopidogrel on cardiovascular death was significantly higher in patients implanted with drug-eluting stent. CONCLUSIONS: In patients undergoing PCI, LR to clopidogrel assessed by VASP-FCT is an independent predictor of cardiovascular death at the PRI cutoff value of > or =61%. The LR clinical impact seems to be dependent on the type of stent implanted.

Diabetes and the platelet: toward new therapeutic paradigms for diabetic atherothrombosis.

Atherothrombosis--defined as atherosclerotic lesion disruption with superimposed thrombus formation--is a leading cause of death in patients with diabetes mellitus. Platelets play a pivotal role in atherothrombosis and platelets of diabetic patients are hyperreactive. Numerous studies have investigated the usefulness of antiplatelet therapy for primary and secondary prevention of atherothrombotic events in diabetic patients. However, there are limited evidences that aspirin may be effective in the reduction of atherothrombotic complication in this population. Additionally, dual antiplatelet therapy with aspirin and clopidogrel has been suggested to be harmful. In contrast, the role of antiplatelet therapy in secondary prevention after ischemic cardiac events is well established in diabetes. Glycoprotein IIb/IIIa receptor antagonists can reduce mortality in diabetic patients committed to undergo percutaneous coronary intervention (PCI). Upregulation of P2Y(12) signalling occurs in hyperglycemia, and the relevance of platelet P2Y(12) receptor inhibition with prasugrel in reducing adverse events following PCI has been recently suggested. Besides platelet activation, several other mechanisms may be involved in the pathophysiology of diabetic atherothrombosis. Tissue factor (TF)-bearing procoagulant microparticles (MPs) are a heterogeneous population of membrane-coated vesicles released by several cell lines upon activation or apoptosis. There is converging evidence that MPs and MP-associated TF activity are upregulated in patients with diabetes mellitus and can participate actively in promoting atherothrombotic complications. In this context, drugs that may reduce the release of microparticles and/or their thrombogenic capacity has the potential to improve upon current antiplatelet therapy, possibly resulting in lower adverse events rates in diabetic individuals.

Importance of inflammation and neurohumoral activation in Takotsubo cardiomyopathy.

BACKGROUND: To gain more insight into the involvement of inflammatory response and neurohumoral activation in Takotsubo cardiomyopathy (TTC), we investigated C-reactive protein (CRP), leukocytes, plasma catecholamines levels, iodine 123 meta-iodobenzylguanidine (123I-mIBG) myocardial uptake, myocardial perfusion (thallium 201 [201Tl] or technetium [Tc] 99m-tetrofosmin myocardial single photon emission computed tomography [SPECT]), and metabolism (fluorine 18-fluorodeoxyglucose positron emission tomography). METHODS AND RESULTS: Inflammatory status and brain natriuretic peptide (BNP) levels in 17 patients with TTC were compared with 14 age-matched patients. In TTC, elevated levels of CRP were evidenced on admission, reaching a peak in the following days (P < .01). CRP levels were correlated to baseline left ventricular ejection fraction (LVEF) and BNP levels (P < .05). Leukocytes were correlated to BNP and noradrenaline levels. Myocardial 123I-mIBG SPECT showed a reduced activity in the midventricle and apex corresponding to 35% +/- 23% of the total myocardial mass, partially reversible at follow-up. An identical pattern was retrieved when assessing myocardial glucose metabolism. At rest, no relevant abnormalities of myocardial perfusion could be evidenced at the subacute phase. CONCLUSION: Inflammatory status in TTC was related to LVEF impairment and to the extent of neurohormonal activation. The hypothesis of a catecholamine-induced myocardial "stunning" is emphasized by the evidence of a reduced 123I-mIBG myocardial activity, impairment of myocardial glucose metabolism, and wall motion kinetic after the same temporospatial distribution.

Lower circulating Sta-Liatest D-Di levels in patients with aortic intramural hematoma compared with classical aortic dissection.

OBJECTIVE: To compare the diagnostic value of circulating Sta-Liatest D-Di levels in classic acute aortic dissection (AAD) and in aortic intramural hematoma (AIH), a variant of AAD without a patent false lumen. DESIGN: Single-center retrospective case-control study. SETTING: University Hospital of Strasbourg, France. PATIENTS: Ninety-four consecutive patients with both confirmed AAD and d-dimer measurements at entry were included. d-dimer levels were assayed by the immunoturbidimetric method Sta-Liatest D-Di (Diagnostica Stago, Asnieres sur Seine, France). INTERVENTION: Patient characteristics and clinical evolution were analyzed. MEASUREMENTS AND MAIN RESULTS: Eighty-four patients (89%) presented a classic AAD with patent false lumen and ten (11%) presented an AIH. Clinical presentation did not differ between the two groups. The mortality rate was 0% in AIH and 26% in classic AAD. d-dimer levels were significantly lower in patients with AIH (median, 1230 ng/mL; interquartile range, 685-2645 ng/mL) than in patients with AAD with patent false lumen (median value, 9290 ng/mL; interquartile range, 3890-20,000 ng/mL; p = 0.008). All patients with AAD and patent false lumen had d-dimer levels above the threshold of 400 ng/mL (sensitivity 100%). However, one patient with AIH presented d-dimer levels below the threshold. Therefore, the sensitivity of the d-dimer test in detecting AIH was 90%. CONCLUSIONS: Sta-Liatest D-Di levels are lower in AIH than in AAD with patent false lumen. This test can quite possibly be negative in the case of intramural hematoma. This feature must be considered when interpreting d-dimer levels in patients with acute aortic syndrome.

Increased levels of procoagulant tissue factor-bearing microparticles within the occluded coronary artery of patients with ST-segment elevation myocardial infarction: role of endothelial damage and leukocyte activation.

OBJECTIVE: During myocardial infarction, platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MPs) in the bloodstream. Few data are available on the potential role played by MPs in coronary atherothrombosis. In the present study, we investigated the levels and cellular origins of MPs within the occluded coronary artery of patients with ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty (PCI). METHODS: A total of 12 patients with STEMI treated by primary PCI within 24h of symptom onset were included in this study. MPs procoagulant activity and cellular origin were characterized within the occluded coronary artery before PCI (C(0)), after restoration of the epicardial blood flow (C(1)), and in blood collected from the femoral artery (F). RESULTS: Levels of leukocyte-derived CD11a(+) MPs, endothelial-derived CD105(+) MPs, and tissue factor (TF)-bearing MPs were significantly higher within the occluded coronary artery than in peripheral blood samples. Restoration of the epicardial blood flow led to a significant reduction of procoagulant CD11a(+) and CD105(+) MPs by 30% and 42%, respectively (p<0.05). CONCLUSIONS: Elevation of procoagulant MPs within the occluded coronary artery of patients with STEMI suggests their pathophysiological role in coronary atherothrombosis.

Endothelial cell activation contributes to the release of procoagulant microparticles during acute cardiac allograft rejection.

BACKGROUND: Circulating procoagulant microparticles are reliable markers of vascular damage. The microparticle phenotypes provide additional information reflecting the nature of cell injury. This study assessed procoagulant microparticle levels and phenotypes in the diagnosis of acute allograft rejection after heart transplantation. METHODS: Microparticles were prospectively investigated in the venous blood of 64 heart transplant patients, 23 with allograft rejection mainly of low score, and 41 without a rejection episode. Plasma concentrations of cytokines, cytoadhesins, and platelet activation markers were determined. RESULTS: By univariate analysis, the mean time elapsed from heart transplant, cold ischemia time, E-selectin-, Fas- and tissue factor-bearing microparticles were associated with allograft rejection. By multivariate analysis, E-selectin-microparticle levels appeared independently associated with allograft rejection, even when other significant variables were included in the model (odds ratio, 9.8; 95% confidence interval, 1.36-71.4; p = 0.023). CONCLUSION: The pattern of procoagulant microparticles released during acute allograft rejection suggests endothelial cell activation and Fas-mediated apoptosis. E-selectin-bearing microparticles appeared as an independent marker of acute allograft rejection that was still informative after adjustment for graft characteristics.

Diagnostic and prognostic value of circulating D-Dimers in patients with acute aortic dissection.

OBJECTIVE: We sought to determine whether assessing D-Dimer might be helpful for the management of acute aortic dissection (AAD). DESIGN: Single-center retrospective case-control study. SETTING: University Hospital of Strasbourg France. PATIENTS: Patients were 94 consecutive patients admitted to our institution with confirmed AAD and in whom D-Dimer test had been performed at presentation. These patients were matched with 94 controls presenting with clinical suspicion of dissection, which was later ruled out. INTERVENTIONS: Patient characteristics and clinical course were analyzed. MEASUREMENTS AND MAIN RESULTS: Ninety-three (99%) patients with AAD had elevated D-Dimer (>400 ng/mL) with a median D-Dimer value of 8610 ng/mL (interquartile range, 2982-20,000 ng/mL). Receiver operating characteristic curves analysis showed that D-Dimer, but not C-reactive protein, troponin, lactate dehydrogenase, or leukocyte count, was predictive of a diagnosis of AAD, with a sensitivity and specificity of 99% and 34%, respectively. D-Dimer concentration positively correlated with the anatomical extension of the dissection to the different segments of the aorta (R = .47, p < .0001). A positive relationship was observed between D-Dimer and in-hospital mortality rate among patients with AAD (p = .037). On multivariate analysis, the independent predictors of in-hospital mortality were the presence of pericardial effusion (odds ratio, 6.80; confidence interval, 1.87-27.60), D-Dimer >5200 ng/mL (odds ratio, 5.38; confidence interval, 1.27-30.87), and female gender (odds ratio, 4.96; confidence interval, 1.39-19.95). CONCLUSIONS: D-Dimers are elevated in patients with AAD and provide valuable diagnostic and prognostic information. In patients with acute chest pain and elevated D-Dimer, a diagnosis of AAD should also be considered. D-Dimer might be a useful complementary tool to the current diagnostic work-up of patients with suspected AAD.