106 Determinants of B-type natriuretic peptide levels and left atrial volume in stable patients in sinus rhythm: an echocardiographic-catheterization study

BackgroundB-type natriuretic peptide (BNP) (Advia Centaur System) and left atrial volume index (LAVi) are regarded as powerful markers of global myocardial function. Several confounding factors are known to potentially influence this relation. The aim of the present study was to evaluate the determinants of BNP and LAVi in the same population of stable patients referred for catheterism.Methods74 consecutive patients were included. Exclusion criteria were arrhythmias, acute coronary syndrome, exacerbation of heart failure and severe left-sided valve disease. All the data were obtained within the same morning for each patient. All following variables were tested: age, gender, body mass index, systolic arterial pressure, heart rate, LV ejection fraction (LVEF), LV mass index (LVM), significant mitral regurgitation (MR), serum hemoglobin (Hb), creatinine clearance (CC), LV end-diastolic pressure (LVEDP), extent of coronary disease.ResultsUnivariate determinants of BNP were age, LVEF, LVM, MR, LVEDP, extent of coronary disease, Hb and CC. By multiple regression analysis, the independant determinants of BNP were age, LVEDP and LVEF (p<0,005 for all). Univariate determinants of LAVI were age, significant MR, LVM, LVEF and LVEDP. By multiple regression analysis, the independent predictors were LVM and LVEDP (p=0,001 for all). BNP was not predicted by LAVi in the multivariate model.ConclusionOur study confirms that both BNP and LAVi can be used as markers of global myocardial dysfunction in stable patients in sinus rhythm. However, age must be taken into consideration before interpreting BNP results

021: Clopidogrel low response and correlation between the different tests: light transmission aggregometry, VerifyNow-P2Y12 and V ASP

BackgroundClopidogrel low response correlates with poor prognosis after percutaneous coronary intervention (PCI). Many biological tests are currently available to test the clopidogrel response. However, the presence of any correlation between the different tests is today poorly reported.MethodsIn this prospective study, clopidogrel response was assessed in 100 consecutive patients. All patients were tested between 18h and 24h after a600mg clopidogrel loading dose using 3 different tests: light transmission aggregometry with 10μmol ADP (LTA, results expressed as platelet inhibition percentage), VerifyNow-P2Y12 (VN, results expressed as PRU) and vasodilatator stimulated phosphoprotein (VASP, results expressed as IRP). Patients under chronic clopidogrel therapy were excluded.ResultsThe mean platelet inhibition percentage, PRU value and IRP value were 38.5±13% by LTA, 178±89 PRU by VN and 52±21% by VASP. When results were analyzed as continuous variables, there was a good correlation between the different tests: LTA/VN (R2=0,642, p<0,001), LTA/VASP (R2=0,409, p<0,001) and VN/VASP (R2=0,616, p<0,001). However, when results were analyzed as pre-specified cut-off points to define patients as “low or good responders” (according to the literature: 50% for LTA, 235 PRU for VN and 50% IRP for VASP), only 47% of the patients were defined as “good” or “low responders” by the 3 tests. Altogether, 33% of the patients were defined as “low responders” by only 1 test, 20% by 2 tests and only 16% by the 3 tests.ConclusionIf the correlation between the different tests is good when results are analyzed as continuous variables, each individual is rarely (less than 50%) defined as “low or good responder” by all the 3 tests when recognized cut-off values are used. In that way, a sole test might not be sufficient to manage antiplatelet therapy in an individual patient

TCT-747 Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention: Systematic review and meta-analysis

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056: Biological efficacy of a 600mg loading dose of clopidogrel in ST-elevation myocardial infarction

BackgroundOptimal platelet reactivity (PR) inhibition is critical to prevent thrombotic events in primary percutaneous coronary intervention (PCI). We aimed to determine the relationship between high on-treatment platelet reactivity (HTPR) and ST-elevation myocardial infarction (STEMI) following a 600mg loading dose (LD) of clopidogrel.Methods and resultsWe performed a prospective monocentre study enrolling patients on clopidogrel undergoing PCI. The VASP index was used to assess PR inhibition after clopidogrel LD. HTPR was defined according to the consensus as a VASP index ≥50%. The present study included 833 patients undergoing PCI. Most patients had PCI for an acute coronary syndrome (58.7%). The mean VASP index was 50±23% with a large inter-individual variability (range: 1–94%). Patients with a VASP index ≥50% were significantly older (p=0.03), with a higher BMI (p<0.001), more often diabetic (p=0.03), taking omeprazole (p=0.03), admitted for an ACS and with a high fibrinogen level compared to good responders (VASP<50%). In multivariate analysis BMI, omeprazole use, acute coronary syndrome and high fibrinogen level (p<0.001) remained significantly associated with HTPR. Of importance, in this analysis STEMI was independently associated with HTPR when compared with the other forms of ACS (NSTEMI and unstable angina) with an odd ratio of 2.14 (95% CI: 1.3 –3.5; p=0.003).ConclusionSTEMI is associated with high on-treatment platelet reactivity following 600mg of clopidogrel. The present results suggest that 600mg of clopidogrel may not be able to achieve an optimal PR inhibition in STEMI patients undergoing PCI and more potent drugs may be preferred

Impact of initial clinical presentation on clopidogrel low response

SummaryBackgroundLarge interindividual variability exists in clopidogrel response. Clopidogrel low response correlates with poor prognosis after percutaneous coronary intervention. Some authors also suggest intraindividual variability over time.AimTo assess the impact of initial clinical presentation on clopidogrel low response.MethodsIn this prospective study, clopidogrel response was assessed in 100 patients. Fifty patients presenting with acute coronary syndromes (ACS group) were compared with 50 patients with stable coronary artery disease matched 1:1 for age, sex, body mass index and diabetes (stable group). All patients were tested 18–24h after a 600mg loading dose of clopidogrel using the VerifyNow-P2Y12 test (results expressed as platelet reaction units [PRUs]). Patients under chronic clopidogrel therapy or treated with glycoprotein IIb/IIIa inhibitors, bivalirudin or thrombolytics were excluded.ResultsMean age was 61±12 years in each group; 28% of patients in each group were diabetic; mean body mass index was 27.6±5.6kg/m2 in the ACS group and 27.9±5.9kg/m2 in the stable group (p=0.80). Mean PRU values were 197±81 in the ACS group and 159±94 in the stable group (p=0.03). By multivariable analysis, the ACS group was significantly associated with a higher PRU value (p=0.02). There were significantly more clopidogrel low responders (PRU value>230) in the ACS group (38% vs. 18%; p=0.04).ConclusionOur study confirms that initial clinical presentation, especially ACS, is a strong predictor of clopidogrel low response; this suggests that the evolution of coronary artery disease for one patient influences the clopidogrel response over time. These results are in accordance with recent trials showing a benefit for more aggressive antiplatelet therapy in ACS patients

Is abnormal myocardial repolarization associated with the occurrence of malignant tachyarrhythmias in Takotsubo cardiomyopathy?

Background: Abnormalities of cardiac repolarization are a hallmark of Takotsubo cardiomyopathy (TC), but their association with the occurrence of syncope and ventricular tachyarrhythmias is unknown. This study sought to assess the relationship between myocardial repolarization and malignant tachyarrhythmias in TC.Methods: Clinical data and electrocardiographic repolarization parameters of 28 patients with TC and ventricular tachyarrhythmias (n = 26) or syncope (n = 2) were compared to data from 20 randomly selected patients with TC but without ventricular tachyarrhythmias or syncope.Results: Study patients had signifi cantly lower ejection fraction (EF) compared with controls (35 ± 14% vs. 46 ± 10%, p = 0.006). On day 1, no signifi cant differences in repolarization parameters were observed. However, in the subgroup with ventricular fi brillation ([VF]; n = 10), Tpeak-Tend in lead V6 was significantly prolonged (97 ± 20 vs. 85 ± 19 ms; p = 0.04). Similarly, in the subgroup with torsade de pointes ([TdP]; n = 5) Tpeak-Tend in lead V4 wasprolonged (127 ± 21 vs. 94 ± 27 ms; p = 0.001). On day 3, Tpeak-Tend in lead V3 (130 ± 51 vs. 105 ± 21 ms, p = 0.049) and Tpeak-Tend dispersion (56 ± 33 vs. 36 ± 21 ms; p = 0.03) were signifi cantly longer in study patients. The difference in Tpeak-Tend in lead V3 was borderline in the VF subgroup, but significant in the subgroup with TdP. The latter grouphad also longer Tpeak-Tend in lead V4 and longer corrected QT interval in leads V3 and V4.Conclusions: Patients with TC who experience malignant tachyarrhythmias have lower EF and a more pronounced alteration of the spatial dispersion of ventricular repolarization

039: Platelet reactivity predicts both ischemic and bleeding events at one year follow-up in acute coronary syndome patients receiving prasugrel

There are evidences of a link between platelet reactivity inhibition and thrombotic and bleeding events. We have previously demonstrated that PR after prasugrel loading dose (LD) predicts short-term thrombotic events. We aimed to further investigate the relationship between PR under prasugrel and one-year thrombotic and bleeding events.MethodPatients were prospectively included in this multicentre study if they had a successful PCI for an acute coronary syndrome (ACS) and received prasugrel. Vasodilator-Stimulated Phosphoprotein (VASP index) was measured after prasugrel LD. Endpoint included the rate of thrombotic events (cardiovascular death, myocardial infarction and stent thrombosis) and bleeding events (TIMI) at one year.ResultsThree hundreds and one patients were enrolled. Nine patients (3%) were lost to follow-up at one year. The rates of thrombotic and bleeding events at one year were 7.5 and 6.8% respectively. The mean VASP index after a 60mg LD of prasugrel was 34}23% and 76 patients (25%) were considered as having high on-treatment platelet reactivity (HTPR). Patients with HTPR had a higher rate of thrombotic events compared to good responders (19.7 vs 3.1%;p<0.001). Patients with a minor or major non-CABG related TIMI bleeding had lower PR compared to patients with no bleeding events (21}18 vs 35}23%;p=0.008). In multivariate analysis, the VASP index predicted both thrombotic and bleeding events (OR: 1.44 (95% CI: 1.2–1.72; p<0.001 and 0.75 (95% CI: 0.59–0.96;p=0.024 (respectively, per 10% increase)).ConclusionPlatelet reactivity measurement after prasugrel LD predicts both ischemic and bleedings events at one year follow-up for ACS patients undergoing PCI

International Expert Consensus on Switching Platelet P2Y(12) Receptor-Inhibiting Therapies

Dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y(12) inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y(12) inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y(12) inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y(12) inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y(12) inhibitors

Beta-blocker management in patients admitted for acute heart failure and reduced ejection fraction: a review and expert consensus opinion

The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings

Nouveaux bio-marqueurs predictifs de la thrombose et de la restenose chez les patients coronariens traites parangioplastie coronaire avec implantation d'une endoprothèse.

L’angioplastie coronaire est la première forme de revascularisation coronaire. Elle présente cependant 2 limites qui restreignent encore son utilisation : la thrombose et la resténose de stent. La thrombose de stent est un événement précoce associé à une mortalité élevée. Les plaquettes y jouent un rôle déterminant. Le développement de tests fonctionnels plaquettaires permettant d’analyser le niveau de réactivité plaquettaire sous traitement a permis de mettre en évidence les limites de celui-ci sur le plan biologique. Nous avons démontré l’impact clinique de l’utilisation de ces tests dans la prédiction et la réduction du risque de thrombose de stent chez des patients traités par angioplastie coronaire. La resténose est quant à elle une complication tardive de l’angioplastie coronaire avec implantation d’un stent non-actif. Sa physiopathologie repose sur des mécanismes de lésion et de régénération endothéliale. Des marqueurs endothéliaux circulants ont récemment été développés. Nous avons montré qu’ils pouvaient permettre d’évaluer la lésion et la régénération endothéliale induite par une angioplastie coronaire. Les cellules endothéliales circulantes s’élèvent transitoirement après l’angioplastie et ce de façon variable en fonction de la réactivité plaquettaire sous traitement démontrant les interactions étroites entre ces différents acteurs. Dans le même temps, on observe une mobilisation de progéniteurs d’origine médullaire suite à l’angioplastie. Nos travaux suggèrent un rôle clé de la régénération endothéliale dans la cicatrisation vasculaire après angioplastie. En effet, il apparait que la proportion de progéniteurs de profil de différenciation endothélial en réponse à l’angioplastie coronaire détermine la survenue d’une resténose intra-stent. Ces données ouvrent la voie à une meilleure compréhension des mécanismes physiopathologie menant à la resténose mais aussi à des perspectives thérapeutiques intéressantes.Percutaneous coronary intervention is the most commonly used revascularization technique. However it has 2 main complications limiting its widespread: stent thrombosis and in stent restenosis. Stent thrombosis is an early event associated with a high mortality rate. Platelets are key in its physiopathology. The availability of platelet function tests allowing to determine platelet reactivity levels under therapy showed a variable ant platelet effect following aspirin and clopidogrel intake. We further demonstrated that tailoring anti platelet therapy according to platelet function tests results decrease the rate of stent thrombosis following PCI without increasing bleedings. In stent-restenosis is a late complication of PCI with bare metal stents. The pathophysiology of in-stent restenosis is dependent on the lesion and regeneration of the endothelium. Circulating endothelial biomarkers have recently been developed. We have demonstrated that this marker allow to evaluate the lesion and regeneration of the endothelium following PCI. We evidenced a transient increase in circulating endothelial cells following PCI which is dependent on the level of platelet reactivity inhibition demonstrating the interaction between platelets and the endothelium. At the same time, PCI induces mobilization of progenitor cells which is detectable early after the intervention. Our work suggests that these progenitor cells have a key role in endothelial regeneration after PCI. We evidenced for the first time that the proportion of endothelial progenitor cells among progenitor cells mobilized after PCI determine the occurrence of in stent restenosis. Altogether these data give critical inside into vascular regeneration after PCI in human and on the mechanisms associated with in stent restenosis thus providing new potential therapeutic target