Bertrand Ledermann

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

Optical Coherence Tomography Evidence of Spontaneous Healing of an Intramural Coronary Hematoma

A 57-year-old woman with no cardiovascular risk factors was admitted to our institution for noneST-elevation myocardial infarction. An admission electrocardiogram showed inverted negative T waves and a significant elevation of ultrasensitive troponin. A transthoracic echocardiogram showed severe apical hypokinesia with a 45% left ventricular ejection fraction. A coronary angiogram revealed a nonsignificant lesion of the mideleft anterior descending artery (Fig. 1A) without other lesions. Optical coherence tomography (OCT) confirmed an extensive left anterior descending hematoma without intimal tear (Fig. 1, B and C). No angioplasty was proposed given its location and extension. Angiographic (Fig. 1D) and OCT controls (Fig. 1, E and F) were obtained at 1 year and showed the complete healing of coronary hematoma. Intramural coronary hematoma has been reported to be a very rare cause of acute coronary syndrome and is often

0098: One year incidence and clinical impact of bleeding outcomes in STEMI patients treated by prasugrel or clopidogrel in real life: the BLEED-MI study

Purposes The aim of this study was to evaluate one-year incidence of bleeding events and their impact on compliance in patients admitted for ST Elevation Myocardial Infarction (STEMI) and treated by prasugrel or clopidogrel in « real-world ». Methods Patients admitted for a STEMI were treated by either clopidogrel or prasugrel according to the physician with respect of guidelines. The primary endpoint was the first occurrence of bleeding events within 12 months assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire focused on bleeding events. Topography bleedings, causes of premature cessation and ischemic events were also compared. Results 390 patients were enrolled, 211 in prasugrel group and 179 in clopidogrel group. Patients in the prasugrel group were younger, with higher body weight and were more frequently men. At 12 months, a bleeding complication occurred in 40% of patients regardless of its severity or treatment prescribed. Major bleedings (BARC 3) were significantly lower with prasugrel than clopidogrel (1% versus 6%, p=0.001). Minimal bleedings (BARC 1) were more frequent in clopidogrel group than prasugrel group (respectively 27% and 18%; p=0.05). However BARC 2 bleedings occurred more often in prasugrel group (14% versus 6%, p=0.01) (figure). Subcutaneous and gastrointestinal haemorraghes were the most frequent. Over one-year, the rate of cessation was 18% in the prasugrel group and only 10% in the clopidogrel group (p=0.04). Respectively for prasugrel and clopidogrel, rates of recommend discontinuation were 10% and 4% (p=0.02) and of disruption were 8% and 5% (p=0.3). Despite more frequent discontinuation, mortality remains very low in the prasugrel group (0.5% versus 7%, p=0.0003). Conclusion In real-world, in a low bleeding risk population, the rate of major bleedings with prasugrel at 12 months was low but nuisance bleedings were frequent with significant impact on premature cessation Download : Download full-size image Abstract 0098 – Figure: 12 months bleedings classification

Évolution des stents pharmacoactifs

L’intervention coronarienne percutanee (ICP) a ete introduite dans les annees 1970 et le premier stent metallique nu (Bare-Metal Stent, BMS) a ete implante par le Pr Jacques Puel en 1986. Les stents a elution de medicaments ( drug-eluting stent, DES) ont ete developpes pour lutter contre la restenose rencontree avec les stents nus. L’arrivee des stents actifs a permis une importante reduction de la restenose intrastent mais, de maniere parallele, une augmentation des thromboses de stent tres tardives a ete observee avec la premiere generation de stents actifs. L’arrivee des stents actifs « nouvelle generation » avec amelioration des plateformes mais aussi des polymeres (biocompatibles ou resorbables) a permis une amelioration des resultats cliniques notamment une reduction des thromboses de stent tres tardives permettant d’envisager une reduction de la duree de la bitherapie antiplaquettaire a 6 mois pour l’angioplastie elective. Dans le meme temps, les stents integralement bioresorbables sont maintenant disponibles, mais ne peuvent pas etre proposes dans toutes les situations cliniques.

075 - Identification of patients at risk for premature discontinuation of oral antiplatelet therapy after elective percutaneous coronary intervention

Background Premature discontinuation of antiplatelet therapy is a major risk factor of stent thrombosis after drug-eluting stent placement leading to an increased risk of death. Objectives We sought to determine by a simple questionnaire the prevalence of patients at risk for premature discontinuation of oral antiplatelet therapy in elective percutaneous coronary intervention (PCI). Methods Patients scheduled for elective PCI underwent a routine interview (RI) and a specific questionnaire (SQ) by two independent physicians the day before the intervention. The SQ was designed to identify bleeding disorders, suspected cancer, planned invasive procedures and self evaluation of compliance. The final decision of drug eluting stent (DES) implantation was made by a third independent physician who performed the planned PCI and who had full access to the patient record. Results At least one contraindication to DES implantation was found in one third of the study population (82/302, 27%) after the RI. All these patients were also identified by the SQ. At total of 31 additional patients were identified by the SQ as non eligible for DES implantation. Active bleeding (n = 14) and scheduled biopsies (n = 4) were the two main contraindications to DES implantation isolated by the SQ. Patients characteristics and angiographic findings identified 59.9% patients (n = 181/302) eligible for a DES implantation. Finally the physician performing the PCI excluded 66.3% of the patients (n = 79/302) who could receive a DES and implanted a bare metal stent (BMS) instead. This decision was based on the findings of the dedicated questionnaire on top of the interview in 30 patients (38%) and in 49 patients (62%) for other reasons. Conclusions In elective PCI, a simple questionnaire used before DES implantation can improve identification of patients at high risk for premature discontinuation of antiplatelet therapy.