Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial.

BACKGROUND: The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI). METHODS: The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status. RESULTS: 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001). CONCLUSION: In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.

[Long-lasting thrombocytopenia induced by glycoprotein IIb/IIIa inhibitor]. / Thrombopénie sévère et prolongée induite par un inhibiteur de la glycoprotéine IIb/IIIa.

INTRODUCTION: Glycoprotein IIb/IIIa inhibitors (anti-GPIIbIIIa) prevent platelet binding to fibrinogen. Transient sometimes-severe thrombocytopenia is a well-known side effect. OBSERVATION: A 71-year-old patient presented severe thrombocytopenia after the administration of tirofiban (anti-GPIIbIIIa). Corticosteroid treatment was initiated at day 10 because of persistence of severe thrombocytopenia with poor platelet transfusion efficacy. Corticosteroid treatment led to platelet recovery evoking an immune mediated mechanism for thrombocytopenia. CONCLUSION: Anti-GPIIbIIIa are associated with a risk of dramatic thrombocytopenia. The underlying mechanism is poorly understood. The management of these usually transient thrombocytopenias is based on platelet transfusion. As report here, in some cases persistent thrombocytopenia can respond to corticosteroids.

Adenosine plasma level correlates with homocysteine and uric acid concentrations in patients with coronary artery disease.

The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 µmol/L vs 0.53 ± 0.14 µmol/L; p < 0.01), HCys (15 ± 7.6 µmol/L vs 6.8 ± 3 µmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations.

Value of CMR in quantification of paravalvular aortic regurgitation after TAVI.

AIMS: To assess the value of cardiac magnetic resonance (CMR) using phase-contrast velocity mapping for paravalvular aortic regurgitation (PAR) quantification. METHODS AND RESULTS: All patients undergoing transcatheter aortic valve implantation (TAVI) in our centre between November 2012 and August 2013, without CMR-contraindication were included. PAR severity was assessed 5 days after TAVI using: transthoracic echocardiography (TTE) and CMR [regurgitant volume (RV), regurgitant fraction (RF)]. Aortic regurgitation (AR) index was obtained during TAVI. Thirty of 51 patients who underwent TAVI were included (COREVALVE, n = 10; or EDWARDS SAPIEN XT, n = 20). At TTE, PAR was mild in 22, moderate in 3, and severe in 5 patients. Reliable phase-contrast images were acquired at the sino-tubular junction for SAPIEN and at the tubular portion of the ascending aorta for COREVALVE. The reproducibility of CMR was high (coefficient of correlation = 0.99 for intra- and inter-operator variability). At CMR, RV, and RF were significantly (P < 0.0005) correlated with AR severity at TTE, with mean RF values at 9.2 ± 7.6% in mild, 20.3 ± 4.2% in moderate, and 46.8 ± 10.8% in severe PAR. A cut-off value of RF < 14% at CMR accurately discriminated mild from moderate/severe (sensitivity: 100%, specificity: 82%). The mean AR index was 29.4 ± 6 for mild and 13.8 ± 5 for moderate/severe PAR. Three patients had a RF > 14% and a low AR index <25 despite a mild PAR at TTE, suggesting an underestimation at TTE. CONCLUSION: CMR is a reproducible, accurate, and reliable method to assess PAR severity. CMR may allow correcting an underestimation at TTE when AR index is doubtful.

Safety and effectiveness of the association ezetimibe-statin (E-S) versus high dose rosuvastatin after acute coronary syndrome: the SAFE-ES study.

BACKGROUND: Statin therapy is a cornerstone therapy for secondary prevention after acute coronary syndrome (ACS). However, the use of these drugs can be limited by side effects, mainly muscular pain. Ezetimibe is a newer lipid-lowering agent, with fewer side effects. AIMS: The present study was designed to compare a commercially available association of ezetimibe and simvastatin (E-S) to high dose Rosuvastatin on cholesterol and muscular enzyme levels and occurrence of muscular pain. METHODS: All consecutive ACS statin-naïve patients with LDL cholesterol (LDL-C)>100mg/dL randomly received either high dose statin (Rosuvastatin 20mg) or E-S 10/40-mg. All patients had one-month follow-up with biological testing and clinical examination. We compared the two groups on the biological efficiency and incidence of muscular pain. RESULTS: One hundred and twenty-eight patients were randomized; 64 received E-S and 64 Rosuvastatin. In the two groups, the lowering of LDL-C level (Δ=51%) at one month was significant (P<0.01) without any difference in the rate of lowering on LDL-C or HDL-C suggesting that E-S is as effective as high dose Rosuvastatin (P=0.77 and P=0.99). The rate of patients reaching the objective of LDL-C<100mg/dL (45%) and LDL-C<70mg/dL (51%) was not different in the two clusters (P=0.65). Incidence of muscular pain was 15% higher in patients treated with Rosuvastatin (P=0.01) without any difference on CPK level (P=0.6). CONCLUSION: Using an association of E-S in an effective alternative strategy to high dose Rosuvastatin with a lower incidence of muscular pain, which might impact adherence to medication after ACS.

Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat.

OBJECTIVE: To assess epicardial fat volume (EFV), myocardial TG content (MTGC) and metabolic profile in severely obese patients, and to determine whether ectopic fat depots are linked to metabolic disorders or myocardial function. RESEARCH DESIGN AND METHODS: Sixty-three subjects with normal LV function and no coronary artery disease, including 33 lean (BMI: 21.4 ± 2.0 kg m(-2)) and 30 obese (BMI: 41.8 ± 6 kg m(-2)) patients, underwent 3-T cardiovascular MRI, and anthropometric, biological and visceral abdominal fat (VAT) assessments. EFV was measured by short-axis slice imaging and myocardial (intra-myocellular) TG content was measured by proton magnetic resonance spectroscopy. RESULTS: EFV and MTGC were positively correlated (r=0.52, P<0.0001), and were both strongly correlated with age, BMI, waist circumference and VAT, but not with severity of obesity. EFV and MTGC were significantly higher in obese patients than in lean controls (141 ± 18 versus 79 ± 7 ml, P=0.0001; 1.0 ± 0.1 versus 0.6 ± 0.1%, P=0.01, respectively), but some differences were found between the two cardiac depots: EFV was higher in diabetic obese subjects as compared with that in non-diabetic obese subjects (213 ± 34 versus 141 ± 18 ml, P=0.03), and was correlated with parameters of glucose tolerance (fasting plasma glucose, insulin and HOMA-IR), whereas MTGC was not. EFV and MTGC were both associated with parameters of lipid profile or inflammation (TGs, CRP). Remarkably, this was VAT-dependent, as only VAT remained independently associated with metabolic parameters (P<0.01). Concerning myocardial function, MTGC was the only parameter independently associated with stroke volume (ß=-0.38, P=0.01), suggesting an impact of cardiac steatosis in cardiac function. CONCLUSIONS: These data show that VAT dominates the relationship between EFV, MTGC and metabolic measures, and uncover specific partitioning of cardiac ectopic lipid deposition.

Aspirin and clopidogrel resistance: should we worry about?

Antiplatelet therapy is a cornerstone of coronary artery disease treatment and prevention. Aspirin and clopidogrel has emerged as the gold standard combination for patients receiving coronary stent and/or suffering from acute coronary syndrome. Despite their efficacy, recurrent events still occur and resistance to antiplatelet drugs might be one of the responsible factors. Aspirin and clopidogrel resistance are emerging entities primarily defined in biological studies by inability of the drug to achieve expected antiplatelet effect based on platelet function tests. Mechanisms of this variability of response remain complex and partially unknown. Moreover, clinical papers linked this biological entity with worse clinical outcomes, and therefore, tailored therapy based on platelet tests has been proposed. Mean while, new antiplatelet drugs will soon change the field while achieving homogeneous degree of platelet inhibition. The present review aims to summarize biological and clinical data about resistance to antiplatelet therapy, and try to estimate how much this might change our prescription in daily clinical practice.

[Acute stent thrombosis due to resistance to clopidogrel ? A case report]. / Implication de la résistance au clopidogrel dans la thrombose aiguë de stent ? A propos d'un cas.

The authors report the case of a 65 year old man who presented with an acute coronary syndrome without ST elevation due to acute stent thrombosis 12 hours after implantation. Recent reports in the literature suggest the role of resistance to antiplatelet drugs in acute, subacute or late stent thrombosis. This patient was included in a protocol studying the response to antiplatelet drugs in patients undergoing coronary stenting and fulfilled the criteria of resistance to clopidogrel. This clinical case illustrates the possible role of "resistance" to antiplatelet drugs in stent thromboses.

[Beneficial effect of a loading dose of 600 mg of clopidogrel on platelet parameters in patients admitted for acute coronary syndrome]. / Bénéfice d'une dose de charge de 600 mg de clopidogrel sur les paramètres plaquettaires chez les patients admis pour syndrome coronaire aigu.

INTRODUCTION: Despite the beneficial effect of an aspirin-clopidogrel combination in acute coronary syndrome, the incidence of ischaemic recurrences remains significant and very probably implicates a variability in the response to anti-platelet agents. OBJECTIVE: We sought to demonstrate the evidence for a beneficial effect, in terms of anti-platelet effect, of a higher loading dose of 600 mg of clopidogrel compared to the usual 300 mg in patients admitted to our centre with acute coronary syndrome. MATERIALS AND METHODS: Platelet reactivity was evaluated with the ADP 10_mol test and the degree of platelet activation by the expression of P-selectin. 178 consecutive patients admitted for acute coronary syndrome received 250 mg of intravenous aspirin together with either a loading dose of 300 mg of clopidogrel (n = 104) or 600 mg (n = 74) administered 12 to 24 hours prior to coronary angiography. RESULTS: The patients who received 600 mg of clopidogrel had an average aggregation intensity to ADP and a rate of platelet high reactivity post treatment that was significantly lower [48+20 vs 58+18, p = 0.0011 and 11 patients (15%) vs 26 patients (25%), p = 0.0003 respectively]. The degree of platelet activation evaluated with P-selectin was significantly lower in patients receiving 600mg [0.33 + 0.17 vs 0.50+0.29, p < 0.001]. CONCLUSION: Our study provides evidence for a beneficial effect of a loading dose of 600mg of clopidogrel compared to the usual 300 mg in terms of platelet reactivity and platelet activation post treatment.

[Platelet function after a high dose bolus of tirofiban immediately after coronary angioplasty]. / Etude de la fonction plaquettaire après bolus de tirofiban a haute dose au décours immédiat de I'angioplastie coronaire.

In the TARGET trial, the lower incidence of cardiac events at one month with abciximab compared with tirofiban was attributed to a lack of efficacy in the first hour because of suboptimal dosage. The object of this study was to confirm that high dose tirofibal is associated with over 90% platelet inhibition during the first hour and to analyse the effect of this new dosage on platelet activation. Thirty-three patients treated with clopidogrel and aspirin for an acute coronary syndrome without ST elevation were given before angioplasty a bolus of 25 microg/Kg of tirofiban injected in 3 minutes, followed by an infusion of 0.15 microg/kg/min. Blood samples were taken before the treatment (TO) and at the 45th minute (T1) to measure platelet aggregation induced by ADP, the expression of P-selection, the quantification of circulating monocyte-platelet aggregates and the phospholyration of VASP protein. The results showed that all patients had over 90% (100%) inhibition of platelet aggregation at T1. The expression of P-selection was significantly reduced (T0: 0.195 +/- 0.057 MFI; T1: 0.186 +/- 0.055 MFI, p = 0.03). There was no significant difference in the number of monocyte-platelet aggregates or in the phosphorylation of VASP. In conclusion, a bolus of 25 microg/Kg/3 min of tirofiban provides over 90% inhibition of platelet aggregation in the first hour. The initial platelet proactivator effect at this dosage was shown to have disappeared with an inhibition of platelet activation.

[Endomyocardial fibrosis: a rare case of restrictive cardiomyopathy in a Caucasian female]. / Fibrose endomyocardique: une cause rare de cardiomyopathie restrictive chez une patiente caucasienne.

The authors report the case of endomyocardial fibrosis diagnosed in a young Caucasian female presenting with progressive congestive cardiac failure. The diagnosis was suspected on the echocardiographic, magnetic resonance imaging and cardiac catheterisation findings in association with the clinical presentation. After a short course of symptomatic medical therapy, the patient underwent the only curative treatment of this pathology, surgical endocardectomy and combined valvular surgery. The confirmation of the diagnosis was obtained a posteriori by histopathological examination of the operative findings which showed appearances of endomyocardial fibrosis similar to those observed in tropical regions. The patient was discharged on the eighth postoperative day, much improved clinically, and follow-up at one year was very satisfactory.

High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome.

BACKGROUND AND OBJECTIVES: Low response to antiplatelet therapy may be a risk factor for the development of ischemic complications in patients with non-ST segment elevation acute coronary syndrome (NSTE ACS) undergoing coronary stenting. METHODS: We prospectively studied the platelet response to both clopidogrel and aspirin in 106 NSTE ACS consecutive patients undergoing percutaneous coronary intervention (PCI) with stenting. A single post-treatment blood sample was obtained just before PCI and analyzed by platelet aggregometry using both ADP and arachidonic acid (AA) as agonists to explore the responses to clopidogrel and aspirin, respectively. Patients were divided into quartiles according to the ADP or AA induced maximal intensity of platelet aggregation. Patients of the highest quartile (quartile 4) were defined as the 'low-responders'. RESULTS: Twelve recurrent cardiovascular (CV) events occurred during the 1-month follow-up. Clinical outcome was significantly associated with platelet response to clopidogrel [Quartile 4 vs. 1, 2, 3: OR (95% CI) 22.4 (4.6-109)]. Low platelet response to aspirin was significantly correlated with clopidogrel low response (P = 0.003) but contributed less to CV events [OR (95%CI): 5.76 (1.54-35.61)]. CONCLUSIONS: A post-treatment ADP-induced platelet aggregation performed just before PCI identifies low responders to dual antiplatelet therapy with an increased risk of recurrent CV events.

[Adult apico-aortic shunts. A case followed for 6 years]. / Dérivation apico-aortique chez l'adulte. A propos d'un cas suivi durant 6 ans.

An apico-aortic shunt enables a reduction in the aortic transvalvular pressure gradient. It is recommended for patients with symptomatic severe stenosis when anatomical constraints contra-indicate valvular replacement. The authors report the case of a patient who underwent this uncommon procedure, which was indicated due to previous coronary bypass surgery using both mammary arteries, plus massive calcification of the ascending aorta. Angio-haemodynamic investigation and MRI performed three years and five years respectively following the procedure confirmed its efficiency. An analysis of the few reported series confirms the value of this special procedure.