[Study of the impact of a post-acute coronary syndrome pharmaceutical interview in hospital]. / Étude de l'impact d'un entretien pharmaceutique post-syndrome coronarien aigu à l'hôpital.

OBJECTIVES: Post-acute coronary syndrome pharmaceutical interviews were set up in our establishment. The objective of this study was to assess their impact on patient knowledge and their benefit at one year on medication compliance, cardiovascular risk factors (smoking, overweight, dyslipidemia) and the recurrence rate. METHODS: Two groups were formed, an experimental group of patients who had benefited from pharmaceutical interviews and a control group of patients who had not benefited from them. The knowledge of the patients was measured using a quizz carried out before the interview and one month after for the experimental group, then one year after hospitalization for the two groups. A one-year follow-up of medication compliance assessed, control of cardiovascular risk factors and the rate of recurrence of acute coronary syndrome was carried out in both groups. RESULTS: A significant increase in knowledge (P<0.001) after the pharmaceutical interview and its maintenance over time were observed in the experimental group. One year after hospitalization, in the experimental group, the average score on the knowledge quizz (9.2/10) was significantly higher (P<0.005) than that of the control group (6.6/10); medication compliance was significantly better (P<0.05) and greater smoking cessation was observed. CONCLUSIONS: These encouraging results should be highlighted in order to perpetuate and develop such approaches around patient care.

[Challenges of coronary catheterization after TAVR]. / Difficultés de cathétérisme coronaire après TAVI.

PURPOSE: Coronary catheterization after transcatheter aortic valve implantation (TAVR) may be challenging. The main objective of the study is to assess the feasibility of coronary catheterization and angioplasty according to each type of valve. PATIENTS AND METHOD: We retrospectively studied coronary angiography or percutaneous angioplasty procedures after TAVR in two different centers. The catheterization success of coronary artery was evaluated according to the quality of engagement in ostium and opacification of the artery. Other indicators were collected including catheters used, fluoroscopy and angiography times, DAP and the volume of the contrast agent. RESULTS: Among 1512 TAVR procedures, 33 patients were included. The Sapien 3® valve was implanted in 22 patients and the Evolut® in 11 patients (7 Evolut-R® and 4 Evolut Pro®). Coronary angiography with selective or partially selective catheterization has been successfully performed in all patients with a Sapien 3® valve. In the Evolut® group we identified 3 cases of non-selective catheterization for the right coronary and 1 case for the left coronary. Standard Judkins catheters seem to be the most suitable for both types of valve with very good efficiency. CONCLUSION: The results of our study is promising for the future of TAVR with a coronary catheterization success rate close to 100% with some difficulties for the Evolut® supra-annular valves. Special attention should be paid to the technique of implantation and orientation of cups in the aortic sinus.

[Common femoral artery bailout stenting with covered stent graft due to TAVR vascular complication: Clinical long term follow-up]. / Suivi clinique après implantation d'un stent couvert dans l'artère fémorale commune au décours immédiat d'une complication vasculaire per-TAVI.

BACKGROUND: Vascular complications are frequent in the context of transcatheter aortic valve replacement and may require the implantation of a covered stent graft in the common femforal artery. However, common femoral artery is considered to be at high risk of stent fracture or occlusion due to high mobility of the hip joint. PATIENTS AND METHODS: We analyzed medical records of patients with transcatheter aortic valve replacement related vascular complications between 2015 and 2018, treated with commom femoral artery transluminal angioplasty or surgery. Vascular complications or suspect symptoms were followed up by phone calls. RESULTS: Among 552 patients, 43 patients were included. Twelve (11.6 %) were managed by prolonged balloon inflation, 5 (11.6 %) by first line surgery and 26 (60.4 %) by the implantation of a covered stent graft. Among the latter group, the covered stent graft was efficient in 24 patients (92.3 %). The median follow-up was 430 days [3-1499]. The first-line surgery group had a higher risk of red blood cell transfusion and all causes mortality. At follow-up, no patient had suspicious symptoms of vascular covered stent complication. Four patients (9.3 %) had US-doppler or CT vascular imaging at follow-up, showing no evidence of stent fracture or occlusion. CONCLUSION: In our study, the implantation of a covered stent graft in the common femoral artery was an efficient and safe strategy for the management of transcatheter aortic valve replacement related vascular complications.

Increased risk and severity of unprovoked venous thromboembolism with clustering cardiovascular risk factors for atherosclerosis: Results of the REMOTEV registry.

BACKGROUND: The role of cardiovascular risk factors (CVRF) for atherosclerosis in venous thromboembolic disease (VTE) is controversial. The aim of this study was to evaluate the impact of CVRF and their cumulative effects on the occurrence of unprovoked VTE, severity, recurrence and survival. METHODS AND RESULTS: This is a prospective cohort from the REMOTEV registry including all consecutively hospitalized patients for acute symptomatic VTE. From November 2013 to December 2016, 515 patients with 6months follow-up (FU) were selected for the analysis. Events were classified as unprovoked or provoked VTE. In univariate analysis, hypertension (OR 1.44, [95% CI 1.01-2.06]), diabetes (OR 2.07, [95% CI: 1.25-3.55]) and age (OR 1.94, [95% CI: 1.31-2.88]) were significantly associated with the risk of unprovoked VTE. After adjustment, diabetes (OR 1.82, [95% CI: 1.07-3.18]) and age (OR 1.79, [95% CI: 1.15-2.8]) remained associated with the risk of unprovoked VTE. The proportion of unprovoked VTE increased significantly with the number of CVRF adjusted for thrombophilia (1 CVRF: OR 3 [95% CI: 1.44-6.52]) 2 CVRF: OR 4.33 [95% CI: 2.07-9.49] and ≥3 CVRF: OR 4.58 [95% CI: 2.27-9.7]). The severity of pulmonary embolism was significantly associated with CVRF clustering. There were more VTE recurrences and deaths during the 6months of FU with cumulative CVRF. CONCLUSION: The risks of unprovoked VTE and PE severity are associated with clustering CVRF. The role of cumulative CVRF predominates rather than the specific burden of each of the CVRF in the risk of VTE occurrence.

Vascular access complications in endovascular procedures with large sheaths.

Endovascular procedures, such as transcatheter aortic valve implantation (TAVI), thoracic endovascular aortic repair (TEVAR), and endovascular abdominal aortic repair (EVAR) have been established as promising less invasive therapeutic options. However, despite continuous advances and device improvements, the use of large-sheaths still remains an important challenge, since significant coexisting arterial disease may be encountered in patients undergoing such procedures. Identification of coexisting arterial diseases by optimal preoperative imaging assessment is essential to anticipate these difficulties and avoid the complications by using adequate access options. Should a vascular complication such as iliac rupture occur, vascular interventionists must be aware of salvage procedures to control and treat major complications, such as maintaining wire access across the rupture for occlusion balloon placement and vessel control, while disruption is addressed either through an endovascular or an open approach. The aims of this review are to describe how to prevent vascular complications by optimal preoperative imaging assessment, to detail intraoperative options available for addressing difficult access issues and to discuss how to manage intraoperative major vascular complications.

Microcirculation in hypertensive patients.

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function. This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network. The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease. These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression.

ß-arrestin-1 participates in thrombosis and regulates integrin aIIbß3 signalling without affecting P2Y receptors desensitisation and function.

ß-arrestin-1 (ß-arr1) and ß-arrestin-2 (ß-arr2) are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling. We used genetically-inactivated mice to evaluate the role of ß-arr1 or ß-arr2 in platelet function, P2Y receptor desensitisation, haemostasis and thrombosis. Platelet aggregation, soluble fibrinogen binding and P-selectin exposure induced by various agonists were near normal in ß-arr1-/- and ß-arr2-/- platelets. In addition, deficiency in ß-arr1 or ß-arr2 was not critical for P2Y receptors desensitisation. A functional redundancy between ß-arr1 and ß-arr2 may explain these unchanged platelet responses. Interestingly, ß-arr1-/- but not ß-arr2-/- mice were protected against laser- and FeCl3-induced thrombosis. The tail bleeding times, number of rebleeds and volume of blood loss were unchanged in ß-arr1-/- and ß-arr2-/- mice, suggesting no defect in haemostasis. ß-arr1-/- platelet activation upon adhesion to immobilised fibrinogen was inhibited, as attested by a 37 ± 5% (n = 3, p<0.0001) decrease in filopodia extension, suggesting defective signalling through integrin αIIbß3. ß-arr1 appeared to be located downstream of Src family kinases and to regulate αIIbß3 signalling by increasing Akt phosphorylation. Overall, this study supports a role for ß-arr1 in promoting thrombus formation, in part through its participation in αIIbß3 signalling, and no role of ß-arr1 and ß-arr2 in agonist-induced platelet activation and P2Y receptors desensitisation.

[Usefulness of diastolic deceleration time assessed by transthoracic Doppler measurement in the detection of sustained microvascular obstruction in STEMI patients treated by primary PTCA]. / Intérêt de la mesure du temps de décélération diastolique par Doppler transthoracique dans l'évaluation du phénomène de no-reflow au cours de l'infarctus du myocarde antérieur traité par angioplastie primaire.

AIMS: To assess the value of coronary flow measurement by transthoracic Doppler technique in the detection of "no-reflow" phenomenon. METHODS: Fourteen patients with first anterior wall infarction treated by successful (TIMI3) primary percutaneous angioplasty and left descending coronary artery stenting were investigated. Myocardial perfusion following PCI was assessed by (i) ST-segment resolution, (ii) MRI-detected microvascular obstruction (early hypoenhancement), (iii) coronary flow pattern measurement by transthoracic Doppler technique. RESULTS: Sustained impairment of myocardial perfusion following PCI was observed in a large proportion of the cohort (36% by MRI, 43% by ST regression analysis). Patients with a diastolic deceleration time inferior to 482 ms had higher troponin and CK peak value, higher wall motion index score, lower ST resolution and lower LVEF assessed by MRI. The concordance of the three methods was 80%. CONCLUSION: The measurement of diastolic deceleration time by transthoracic Doppler technique is a reliable technique to identify microvascular obstruction following PCI in acute anterior STEMI. A DDT inferior to 482 ms is associated with sustained "no-reflow" phenomenon.

Impaired inhibition of P2Y(12) by clopidogrel is a major determinant of cardiac death in diabetes mellitus patients treated by percutaneous coronary intervention.

OBJECTIVES: We sought to determine whether low platelet response (LR) to the P2Y(12) receptor antagonist as assessed by vasodilator-stimulated phosphoprotein flow cytometry (VASP-FCT) differentially affects outcome in patients with or without diabetes mellitus undergoing percutaneous coronary intervention. BACKGROUND: While both DM and LR to clopidogrel are known to predict an unfavorable outcome after PCI, the deleterious effect of their association is less well established. The VASP-FCT is specific for the P2Y(12) ADP receptor pathway. In this test, platelet activation is expressed as the platelet reactivity index (PRI). METHODS: Patients were assigned to four different groups according to the presence or not of DM (DM, NDM) and LR to clopidogrel (LR, R). LR was defined as a PRI of >61%, a threshold previously identified as the optimal cut-off value to predict cardiac death following PCI. RESULTS: A total of 436 consecutive patients (163 DM, 273 NDM) were enrolled. The proportion of LR patients was higher in DM (47.9% vs. 35.2% p=0.011). At 9±2 months follow-up, the rates of total and cardiac mortality and possible and overall stent thrombosis were higher in DM-LR patients. Conversely, the cardiovascular outcome of DM-R patients was comparable to that of NDM (-LR or -R) patients. In DM, a multivariate analysis identified LR to clopidogrel (HR 6.09 [1.27-29.08], p=0.023) as the sole independent predictor of cardiac mortality. CONCLUSIONS: In DM patients undergoing PCI, LR to clopidogrel is an independent predictor of cardiac death.

Recurrent form of neurogenic stunned myocardium: is myocardial adrenergic receptor distribution a dynamic process?

Neurogenic stunned myocardium mediated by stress-induced catecholamine acute release is considered as the central causative mechanism of transient left ventricular dysfunction syndrome (TVLDS). Interindividual differences in both LV ß-adrenergic receptor density and sympathetic innervation were proposed to explain the atypical forms of TVLDS. Whether this distribution is independent of age or may vary during ageing still remains unclear. We report a recurrent form of TLVDS characterized by two different patterns. Whilst myocardial receptor distribution or sympathetic innervation appears to follow a dynamic process, the precise determinants of these variations remain largely unknown.

[Myonecrosis and inflammatory response following percutaneous coronary angioplasty. A protective role for betablockers?]. / Myonécrose et majoration de la réponse inflammatoire après angioplastie coronaire. Rôle protecteur des bêtabloquants?

INTRODUCTION: Percutaneous coronary intervention (PCI) is widely used actually for the treatment of coronary disease. Stent implantation in the vessel wall is associated with local healing processes and some myonecrosis. However, little is known about the relationships between systemic inflammatory response, myonecrosis and the patient's and procedural characteristics. OBJECTIVES: (i) To evaluate the level of C-Reactive Protein (hsCRP) and cardiac troponin I (cTnI) elevation after PCI; (ii) to determine the patient's and procedural factors associated with those elevations. METHOD: This is a prospective monocentric study carried out in patients hospitalised for elective PCI or for ACS without cTnI elevation. CRP and cTnI were assessed before, after and 24 hours after the procedure. RESULTS: Thirty-four patients (mean age 64+/-10.9 years; sex ratio 28 males/six females) were included. hsCRP increased in 26 patients (76.4%) and cTnI in 16 patients (47%) after PCI. cTnI elevation did not correlate with inflammatory response. Whereas none of the studied parameters were statistically linked with hsCRP increase, cTnI elevation was significantly associated with AHA-ACC B(2)/C type lesion, the number and the total length of stents implanted, the duration of procedure and treatment by betablockers. Multivariate analysis showed that the independent predictors of cTnI elevation were procedure duration (p=0.032 OR=14.2 CI 95% 7.69-100) and the absence of pretreatment with betablockers (p=0.036, OR=2,6 CI 95% 1.35-35). CONCLUSION: cTnI elevation following PCI is very frequent and related with the duration of the procedure. Our data suggest a protective role of betablockers in the occurrence of cTnI elevation after PCI. Confirmation of the protective role of betablockers in larger cohort is mandatory.

Ex vivo inhibition of thrombus formation by an anti-glycoprotein VI Fab fragment in non-human primates without modification of glycoprotein VI expression.

OBJECTIVES: Glycoprotein (GP)VI is an attractive target for the development of new antithrombotic drugs. Its deficiency protects animals in several models of thrombosis, arterial stenosis and ischemia--reperfusion while inducing no major bleeding tendency. The Fab fragment of one anti-GPVI monoclonal antibody (9O12.2) inhibits all GPVI functions in vitro. The aim of this study was to determine the ex vivo effects of 9O12.2 Fab on hemostasis, coagulation and thrombosis in non-human primates. METHODS AND RESULTS: Blood samples were collected from cynomolgus monkeys before and after (30, 90 and 150 min, 1 and 7 days) a bolus injection of 9O12.2 Fab (4 mg kg(-1)) or vehicle. Platelet counts and coagulation tests (prothrombin time, activated partial thromboplastin time) were not modified following Fab injection. The PFA-100 closure time increased during the first hours and returned to initial values on day + 1. Platelet-bound Fab was detected from 30 min to 24 h after Fab injection without GPVI depletion at any time. Collagen-induced platelet aggregation was selectively and fully inhibited at 30 min. Thrombus formation on collagen in flowing whole blood (1500 s(-1)) was delayed and decreased, and collagen-induced or tissue factor-induced thrombin generation in platelet-rich plasma was profoundly inhibited. CONCLUSION: The anti-GPVI 9O12.2 Fab inhibits thrombus formation ex vivo in non-human primates with a composite effect on platelet activation and thrombin generation in the absence of GPVI depletion.

[Platelet responsiveness to clopidogrel in patients with coronary syndrome. Comparison of platelet aggregation induced by ADP and flow cytometric analysis of intraplatelet VASP phosphorylation]. / Evaluation de la réponse plaquettaire au clopidogrel au cours des syndromes coronariens. Comparaison de l'agrégométrie à l'ADP et de la méthode VASP.

UNLABELLED: Although antiplatelet therapy with ASA-clopidogrel reduces the risk of cardiovascular episodes after PCI, a substantial number of events occur during follow-up. Sustained platelet reactivity under dual antiplatelet therapy was recently associated with increased risk of recurrent atherothrombotic events after PCI. Whereas it appears significant to determine clopidogrel responsiveness, the accurate platelet function assay is still under investigation. OBJECTIVES: (i) to determine the proportion of "low-responders" or "resistants" patients during coronary syndrome (ii) to identify determinants of interindividual variability response to clopidogrel (iii) to compare aggregometry and VASP phosphorylation measured by flow cytometry. Patients were treated by clopidogrel (300 mg loading dose and 75 mg maintenance dose) and ASA (160 mg) (N=27). Additional treatment by GPIIbIIIa antagonists was given to high-risk patients (N=9). Platelet function was monitored by ADP aggregometry (5, 10, 20 microM) and VASP phosphorylation before any treatment by clopidogrel (d0) and at least five days after (d5). The platelet reactivity index (PRI), expressed as percentage, is the difference in VASP fluorescence intensity between resting (+ PGE1) and activated (ADP) platelets. At d5, low responsiveness to clopidogrel was defined by either (i) a PRI > 67.3% corresponding to the mean value -2SD measured in untreated patients (dO) (ii) or an absolute change (delta d0-d5) in aggregation (ADP 10 microM) < to 30%. RESULTS: PRI, platelet aggregometry to ADP was significantly reduced following clopidogrel treatment (P < 0.01). A wide inter-individual variability to clopidogrel was observed at d5 (PRI from 11 to 83%). Whatever the platelet function used, a large proportion of patients were detected as "low-responders" (37% by VASP, 44% by ADP aggregometry). Absolute change in ADP aggregation was correlated to the variation of PRI (R = 0.559; P = 0.02). Contrary to ADP aggregometry, PRI was not influenced by GPIIbIIIa antagonists or prior administration of ASA. However, the conformity of the two methods to evaluate clopidogrel responsiveness was only 66%. No differences in platelet aggregometry could be observed at d5 between "low" and "good-responders" defined by VASP analysis. At d5, a higher PRI value could be detected in male and patients with history of dyslipemia. CONCLUSION: During coronary syndrome, impaired platelet responsiveness to clopidogrel was observed in a large proportion of patients whatever the platelet function assay used. VASP analysis was found insensitive to GPIIbIIIa or aspirin administration. Possible mechanisms linking clopidogrel "resistance" measured by VASP assay and enhanced thrombogenicity remain to be characterized. Indeed, clopidogrel "resistance" defined by VASP analysis was not associated with higher platelet aggregation.

Role of pre-infarction angina and inflammatory status in the extent of microvascular obstruction detected by MRI in myocardial infarction patients treated by PCI.

BACKGROUND/OBJECTIVES: The extent of microvascular obstruction (MVO) during myocardial infarction referred to as the "no-reflow phenomenon", may determine myocardial damage. Our study aimed to investigate the incidence and the influencing factors of MVO in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous intervention (PCI). PATIENTS, METHODS: Using contrast-enhanced MRI, microvascular obstruction was defined as early hypoenhancement. Contrast defects were scored from 0 (no hypoenhancement) to 3 (strong hypoenhancement). 50 patients (56+/-11 years) with STEMI underwent PCI. Contrast-enhanced MRI (6+/-2 days after STEMI) and biochemical parameters were evaluated. RESULTS: Microvascular obstruction (score 1 to 3) was observed in 90% of the patients and major microvascular obstruction (score 2-3) in 54%. In univariate analysis, leukocytes and CRP levels were associated with MVO, whereas pre-infarction angina and prior medication by aspirin or calcium channel antagonist appeared protective. Microvascular obstruction intensity positively correlated with baseline inflammation status assessed by C-reactive protein and leukocytes (rho=0.43 and rho=0.44; p=0.003), the peak of CK (rho=0.56; p=0.01) or Troponin I (rho=0.59; p=0.01) and negatively correlated with LVEF (rho=-0.44; p=0.002). Multivariate analysis identified the absence of pre-infarction angina as the only independent predictor for microvascular obstruction (odds ratio, 8.35, 95% confidence interval 1.27-54.71; p=0.027). CONCLUSION: MRI-detected microvascular obstruction has a high incidence in patients with STEMI treated by primary PCI and determines post-MI LVEF even in patients with post PCI TIMI 3 flow score. Pre-infarction angina appears to be an independent determinant of the extent of MVO detected by MRI.