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Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials.

Objectives The aim of this study was to examine the value of frailty to predict in-hospital major bleeding and determine its impact on mid-term mortality following transcatheter (TAVR) or surgical (SAVR) aortic valve replacement. Background Bleeding complications are harbingers of mortality and major morbidity in patients undergoing TAVR or SAVR. Despite the high prevalence of frailty in this population, little is known about its effects on bleeding risk. Methods A post hoc analysis was performed of the multinational FRAILTY-AVR (Frailty Aortic Valve Replacement) cohort study, which prospectively enrolled older adults ≥70 years of age undergoing TAVR or SAVR. Trained researchers assessed frailty using a questionnaire and physical performance battery pre-procedure and ascertained clinical data from the electronic health record. The primary endpoint was major or life-threatening bleeding during the index hospitalization, and the secondary endpoint was units of packed red blood cells transfused. Results The cohort consisted of 1,195 patients with a mean age of 81.3 ± 6.0 years. The incidence of life-threatening bleeding, major bleeding with a clinically apparent source, and major bleeding without a clinically apparent source was, respectively, 3%, 6%, and 9% in the TAVR group and 8%, 10%, and 31% in the SAVR group. Frailty measured using the Essential Frailty Toolset was an independent predictor of major bleeding and packed red blood cell transfusions in both groups. Major bleeding was associated with a 3-fold increase in 1-year mortality following TAVR (odds ratio: 3.40; 95% confidence interval: 2.22 to 5.21) and SAVR (odds ratio: 2.79; 95% confidence interval: 1.25 to 6.21). Conclusions Frailty is associated with post-procedural major bleeding in older adults undergoing TAVR and SAVR, which is in turn associated with a higher risk for mid-term mortality.

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials.

Objectives This study sought to evaluate the feasibility, safety, and efficacy of the Ultraseal device for left atrial appendage closure (LAAC) (Cardia, Eagan, Minnesota) in patients with nonvalvular atrial fibrillation at high bleeding risk. Background The Ultraseal device is a novel bulb-and-sail designed LAAC device, with an articulating joint enabling conformability to heterogeneous angles and shapes of appendage anatomy. Methods This was a multicenter study including consecutive patients undergoing LAAC with the Ultraseal device at 15 Canadian and European sites. Periprocedural and follow-up events were systematically collected, and transesophageal echocardiography at 45 to 180 days post-procedure was routinely performed in all centers but 3. Results A total of 126 patients (mean age 75 ± 8 years; mean CHA2DS2-VASc score 5 ± 2; mean HAS-BLED score 4 ± 1) were included. The device was successfully implanted in 97% of patients. A major periprocedural adverse event occurred in 3 (2.4%) patients (clinically relevant pericardial effusion [n = 1], stroke [n = 1], device embolization [n = 1]). Ninety percent of patients were discharged on single or dual antiplatelet therapy. Follow-up transesophageal echocardiography was available in 89 (73%) patients, with no cases of large (>5 mm) residual leak and 5 (5.6%) cases of device-related thrombosis (all successfully treated with anticoagulation therapy). At a median follow-up of 6 (interquartile range: 3 to 10) months, the rates of stroke and transient ischemic attack were 0.8% and 0.8%, respectively, with no systemic emboli. None of the events occurred in patients with device-related thrombosis. Conclusions In this initial multicenter experience, LAAC with the Ultraseal device was associated with a high implant success rate and a very low incidence of periprocedural complications. There were no late device-related clinical events and promising efficacy results were observed regarding thromboembolic prevention at midterm follow-up. Larger studies are further warranted to confirm the long-term safety and efficacy of this novel device.

In the race to develop a transcatheter mitral valve, experience with new techniques and devices has resulted in revisiting a previously known complication of surgical mitral valve replacement and r...

Aims Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the ‘smoker’s paradox’ suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. Methods The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. Results Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p Conclusion In contrast to the ‘smoker’s paradox’, current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).

Takotsubo cardiomyopathy (TTC) is a stress-related transient cardiomyopathy. Life-threatening arrhythmias (LTA) can occur and worsen prognosis.The purpose of this study was to assess the incidence and outcome of LTA in TTC, as well as its predictive factors and clinical implications.We studied 214 consecutive cases of TTC over 8 years. The study cohort was divided into 2 groups: those with LTA (LTA group) and those without (non-LTA group). LTA was defined as ventricular tachycardia, ventricular fibrillation, or cardiac arrest.LTA occurred in 23 (10.7%) of patients mainly in the first 24 hours of hospitalization: ventricular tachycardia (n = 2), ventricular fibrillation (n = 11), cardiac arrest (n = 10: 5 asystole, 3 complete heart block, and 2 sinoatrial block). LTAs were associated with lower left ventricular ejection fraction (LVEF) and a high rate of conduction disturbances. In-hospital (39.1% vs 8.9%; P .001) and 1-year mortality (47.8% vs 14.1%; P.001) rates were significantly increased in the LTA group. LVEF and QRS duration105 ms were independent predictors of LTA. In cases where a device was implanted, conduction disturbances persisted after the index event despite complete recovery of LVEF. There was no ventricular arrhythmia recurrence during follow-up.LTAs occur early in patients presenting with TTC and are associated with significantly worse short- and long-term prognosis. Left ventricular impairment and QRS duration105 ms are independent predictors of LTA. Ventricular arrhythmias occurred in the acute phase without further recurrence recorded in hospital survivors, whereas severe conduction disorders persisted during long-term follow-up. These findings may have implications on the choice of device therapy for this specific patient subgroup.

Percutaneous left atrial appendage occlusion (LAAO) for stroke prevention in patients with atrial fibrillation has significantly advanced in the past 2 decades. LAAO has emerged as a feasible and safe alternative to oral anticoagulants in patients who are deemed high risk for bleeding or are ineligible to receive anticoagulation. Herein, the authors review the main design features of the AMPLATZER Amulet device and describe step-by-step technical considerations for implantation of this LAAO device.

Background Paravalvular aortic regurgitation (PVAR) remains a frequent postprocedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high-molecular-weight von Willebrand multimers, primary haemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor–dependent platelet function (closure time [CT] adenosine diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined whether CT-ADP could detect PVAR at 30 days and bleeding complications following TAVR. Methods CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PVAR was defined as a circumferential extent of regurgitation more than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the Valve Academic Research Consortium-2 consensus classification. Results Significant PVAR was diagnosed in 44 out of 219 patients (20.1%). Important reduction of CT-ADP could be found in patients without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1, 95% confidence interval [CI]: 2.5–10.6; p 180 seconds was identified as an independent predictor of major/life-threatening bleeding (HR: 1.7, 95% CI [1.0–3.1]; p = 0.049). Major/life-threatening bleedings were at their highest levels in patients with postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). Conclusion Postprocedural CT-ADP > 180 seconds is an independent predictor of significant PVAR 30 days after TAVR and may independently contribute to major/life-threatening bleedings.

Background Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. Conclusions Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.

Out-of-hospital cardiac arrest (OHCA) remains a major public health issue. Emergency coronary angiography and percutaneous coronary intervention might improve survival, especially when cardiac arrest is caused by acute myocardial infarction (AMI). However, identifying patients with AMI after OHCA remains challenging. The aim of this study was to determine the clinical and ECG criteria in OHCA that may help to identify better the patients with AMI.Consecutive OHCA patients who underwent emergency coronary angiography in our centre between 2009 and 2013 were included in this retrospective single-centre observational study.A total of 177 patients with complete datasets were included. Significant coronary artery disease was found in 71% of the patients, and 43% presented with AMI. The independent predictors of AMI were ST elevation in any lead including aVR (odds ratio (OR) 18.06; 95% confidence interval (CI) 6.6-49.38), chest pain before cardiac arrest (OR 4.05; 95% CI 1.55-10.54) and an initial shockable rhythm (OR 2.99; 95% CI 1.34-6.45). An additive score that included these three predictors yielded a sensitivity and a specificity for detecting AMI of 93% and 63%, respectively.These data suggest that fewer than half of patients with OHCA undergoing emergency coronary angiography present with AMI. The identification of OHCA patients with AMI might be improved by a simple score using post-resuscitation ECG and simple clinical criteria.

Transcatheter aortic valve replacement (TAVR) is now considered as the established treatment of severe symptomatic aortic stenosis in patients deemed to be at high risk of surgical mortality or who are not suitable for surgery. During this decade, TAVR has emerged as a valid alternative to surgical aortic valve replacement in patients at intermediate surgical risk, and several studies are currently being performed to assess whether TAVR can be as effective as surgical aortic valve replacement (SAVR) in low- to intermediate-risk patients.

Reactive oxygen species (ROS) are central bioenergetic markers linked to aortic stenosis (AS) development and severity. We sought to evaluate the time course and impact of ROS assessed by plasmatic superoxide anion (SA) among patients undergoing transcatheter aortic valve replacement (TAVR). Among 106 patients, SA significantly decreased after TAVR. Dropped values were measured 10 min after TAVR (0.590 ± 0.181

With respect to the transfemoral approach, transradial procedures enable a drastic reduction of bleeding events and are associated with a reduction of mortality. Radial artery spasm (RAS) is one of the most common complications and may lead to patient discomfort and procedural failure. Currently, there is no consensus on the optimal sedation protocol to avoid RAS. The aim of this study was to investigate the respective impact of opioids analgesia and inhalation sedation with a 50% nitrous oxide/oxygen premix (Kalinox) on pain and occurrence of RAS during transradial coronary procedures. Consecutive patients undergoing transradial coronary angiography were prospectively enrolled in one, single center observational study (Nouvel H&ocirc, pital Civil, Strasbourg, France). Patients received opioids analgesia or inhalation sedation with Kalinox. The primary endpoints of the study were the incidence of a pain scale &ge, 5/10 and the occurrence of RAS. The secondary endpoints were the incidence of side effects. A total of 325 patients were enrolled (185 in the opioids analgesia group, 140 in the Kalinox group). RAS and pain scale &ge, 5 rates were not significantly different in the opioids analgesia and Kalinox groups (respectively 13.5% vs. 10.0% and 16.2% vs. 11.4%). Headache was more frequently observed in the Kalinox group (6.4% vs. 0.0%, p = 0.002). By multivariate analysis, female gender, BMI &lt, 25 kg/m2, puncture difficulty, the use of plastic needle and 6F sheath were identified as independent predictors of RAS. Procedural inhalation sedation by Kalinox is as safe as opioids analgesia during transradial coronary angiography.

Percutaneous left atrial appendage occlusion (LAAO) for stroke prevention in patients with atrial fibrillation has significantly advanced in the past 2 decades. LAAO has emerged as a feasible and safe alternative to oral anticoagulants in patients who are deemed high risk for bleeding or are ineligible to receive anticoagulation. Herein, the authors review the main design features of the AMPLATZER Amulet device and describe step-by-step technical considerations for implantation of this LAAO device.

Aims:Takotsubo cardiomyopathy (TTC) is a stress-related transient cardiomyopathy. It is unclear whether TTC is associated with poorer prognosis when atrial arrhythmia (AA), atrial fibrillation or flutter, occurs. The purpose of this study was to assess the incidence of AA in patients with TTC, predictive factors of AA, and its association with mortality. Methods and results:We studied 214 consecutive cases of TTC over 8 years. The study cohort was divided into two groups-those with newly diagnosed AA (AA-group) and those without (non-AA group). AA occurred in 24.8% of the patients. The AA group presented with lower left ventricular ejection fraction (LVEF) on admission and higher cardiac arrest rate. Admission and peak levels of troponin, B-type natriuretic peptide (BNP), C-reactive protein (CRP), and leucocytes were higher in the AA group. In-hospital, 30-day, cardiovascular, and all-cause mortality were significantly higher in the AA group. Independent predictors of newly diagnosed AA were troponin peak [odds ratio (OR) 1.03 (1.003-1.06); P = 0.029], CRP peak [OR 1.006 (1.001-1.01); P = 0.026], and LVEF on admission [OR 0.96 (0.93-0.99); P = 0.01]. Newly diagnosed AA was not predictive of mortality. The BNP peak [OR 1.00 (1.000-1.001); P = 0.022] and leucocytes peak [OR 1.095 (1.034-1.16); P = 0.002] were predictive factors of in-hospital mortality. LVEF upon discharge [OR 0.935 (0.899-0.972); P = 0.001] and leucocytes peak [OR 1.068 (1.000-1.139); P = 0.049] were predictive of cardiovascular death. Conclusion:Newly diagnosed AA is frequently observed in patients presenting with TTC and is associated with poorer short- and long-term prognosis. Inflammation, myocardial damage, and LVEF are predictors of AA onset and cardiovascular mortality.

Aim: In percutaneous coronary intervention (PCI)-treated acute coronary syndrome (ACS) patients on clopidogrel therapy, high on-treatment platelet adenosine diphosphate (ADP) reactivity was observed in numerous studies, with significant increases in non-fatal myocardial infarction, definite/probable stent thrombosis, or cardiovascular mortality. Compared to clopidogrel, prasugrel and ticagrelor provide more potent platelet inhibition. Whether new P2Y12 inhibitors reduce thrombotic events in a similar manner compared to the rate observed with appropriate P2Y12 inhibition by clopidogrel must still be determined. This study sought to compare longterm outcomes between clopidogrel responders (platelet reactivity index [PRI] vasodilator-stimulated phosphoprotein [VASP] < 61%) and patients under prasugrel or ticagrelor therapy following PCI-treated ACS. Methods: 730 ACS patients undergoing urgent PCI were prospectively enrolled into two groups: clopidogrel responders (n = 448) and those under ticagrelor or prasugrel therapy (n = 282). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stent thrombosis, and stroke; the secondary endpoint comprised major hemorrhagic events. Results: The median follow-up was 260 ± 186 days. Clopidogrel patients were older and more likely to present non-ST segment elevation myocardial infarction, cardiovascular risk factors, atrial fibrillation, or prior vascular disease. After propensity score matching, the primary endpoint was met in 7.1% of the clopidogrel group and 4.1% of the prasugrel/ticagrelor group (p = 0.43). Minor bleeding events were significantly reduced in the clopidogrel group (1.1% vs. 3%; p = 0.03). In a multivariate analysis, the antiplatelet treatment strategy was not an independent primary endpoint predictor. Conclusion: In PCI-treated ACS patients, clopidogrel therapy and PRI VASP < 61% were not associated with increased risks of thrombotic events compared to prasugrel or ticagrelor therapy.

This study sought to evaluate the feasibility, safety, and efficacy of the Ultraseal device for left atrial appendage closure (LAAC) (Cardia, Eagan, Minnesota) in patients with nonvalvular atrial fibrillation at high bleeding risk.The Ultraseal device is a novel bulb-and-sail designed LAAC device, with an articulating joint enabling conformability to heterogeneous angles and shapes of appendage anatomy.This was a multicenter study including consecutive patients undergoing LAAC with the Ultraseal device at 15 Canadian and European sites. Periprocedural and follow-up events were systematically collected, and transesophageal echocardiography at 45 to 180 days post-procedure was routinely performed in all centers but 3.A total of 126 patients (mean age 75 ± 8 years; mean CHAIn this initial multicenter experience, LAAC with the Ultraseal device was associated with a high implant success rate and a very low incidence of periprocedural complications. There were no late device-related clinical events and promising efficacy results were observed regarding thromboembolic prevention at midterm follow-up. Larger studies are further warranted to confirm the long-term safety and efficacy of this novel device.

Background Periprocedural and late (>30 days) bleedings represent one of the major complications after Transcatheter Aortic Valve Replacement (TAVR) and have been identified as potential area for improved patient care. Objectives To evaluate the impact of ongoing primary hemostasis disorders on late major/life-threatening bleeding complications (MLBCs). Methods Bleedings were assessed according to the Valve Academic Research Consortium-2 (VARC-2) criteria. CT-ADP, a surrogate marker of high molecular weight von Willebrand multimers proteolysis was assessed 24 h after the procedure. Ongoing primary hemostasis disorder was defined by a CT-ADP > 180 s. Results Amongst 372 patients who survived at 30 days, MLBCs occurred in 42 patients (11.3%) at a median follow-up of 383 days (interquartile range 188 to 574 days). MLBCs were mainly of gastrointestinal origin (42.9%) and were associated with increased overall mortality (HR 5.66; 95% CI [3.10–10.31]; P 180 s (27.4 vs. 11.5%; P 180 s (HR 3.08; [1.62–5.81]; P = 0.0005) as independent predictor of MLBCs Table 1 , Fig. 1 ). Conclusion MLBCs after TAVR are frequent and associated with an increased morbidity and mortality. PVL and CT-ADP > 180s were identified as strong predictors for MLBCs. Our findings strongly suggest that the missing link between PVL and the risk of MLBCs is a persistent High Molecular Weight Von Willebrand defect. It may help physician to tailor follow-up and anti-thrombotic regimens of patients and improve clinical outcomes.

SummaryBackgroundIn STEMI patients treated by primary PCI, damage of the microvascular circulation caused by distal embolization of thrombotic material affects the quality of myocardial reperfusion. Important controversies remain concerning the usefulness of the manual thrombectomy to improve myocardial perfusion. The aim of this study is to evaluate the impact of manual thrombectomy on ST resolution as a surrogate of reperfusion extent.MethodsTwo hundred and thirty-nine consecutive STEMI patients with an 70%) resolution of ST segment elevation.ResultsA complete resolution of ST segment elevation occurred in 51.4% of patients in the thrombectomy group and in 35,6% of those in the conventional-PCI group (P=0.018). Thrombectomy strategy was associated with a lower use of stents. Multivariate analysis identified manual thrombectomy (HR=2.08 IC 95% (1.01–4.26); P=0.046), inferior location and short ischemic delay (

a Pole d'activite medico-chirurgicale, Nouvel Hopital Civil, Hopitaux universitaires de Strasbourg, France b Pole Anesthesie-Reanimation Chirurgicale, SAMU, Nouvel Hopital Civil, Hopitaux universitaires de Strasbourg, France c Service de medecine interne, Nouvel Hopital Civil, Hopitaux universitaires de Strasbourg, France d Laboratoire EA 3072: «Mitochondries, stress oxydant et protection musculaire», Institut de Physiologie, Faculte de Medecine, Universite de Strasbourg, France

Except for bleeding complications, vitamin K antagonists (VKAs) are known to have few undesirable side effects. Herein is presented the case of a 45-year-old woman in whom liver damage was induced by fluindione and warfarin after mitral valve replacement. Hepatotoxicity is a rare complication of VKAs, both in the French National and Drug Safety registry and the medical literature. A diagnosis of VKA-induced drug damage was confirmed by the absence of other etiologies, the chronological sequence, recurrence after re-exposure to VKA, and rapid improvements after discontinuation of the drug. Despite possible cross-reactions between VKAs, the re-introduction of acenocoumarol was successfully achieved, with no recurrence of biological disturbances.

High-density lipoproteins (HDL) are involved in reverse cholesterol transport. Results from randomized trials of HDL-targeting therapies, including cholesteryl ester transfer protein (CETP) inhibitors, have shown a lack of benefit in unsegmented populations. These observations could be explained by inter-individual variability of clinical responses to such agents depending on the patients’ genotypes. In parallel, although lowering of LDL cholesterol (LDL-c) with statin therapy reduces the risk of vascular events in a wide range of individuals, inter-individual variability exists with regard to LDL-c-lowering response as well as efficacy in reducing major cardiovascular events. Pharmacogenomic analyses were performed in the dal-OUTCOMES and dal-PLAQUE-2 studies. Beneficial and concordant results were observed in patients with the favorable genotype when treated with the CETP inhibitor dalcetrapib. Similarly, previous studies revealed genetic variants associated with differential LDL-c response to statin therapy. In this review, we discuss the pharmacogenetic determinants of HDL-targeting and statin therapy responses in light of the latest available published data, and their potential therapeutic applications.

The recently reported ANTARCTIC trial by Cayla and colleagues is the latest large-scale study of personalized antiplatelet therapy based on platelet function testing (1). In this open-label, blinded end-point, randomized, controlled trial, the authors ascertained the net clinical benefit of individualized antiplatelet therapy based on platelet function monitoring in elderly patients undergoing stenting (PCI) for an acute coronary syndrome (ACS).

Background Paravalvular aortic regurgitation (PAVR) remains a frequent post-procedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high molecular weight von Willebrand multimers, primary hemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor-dependent platelet function (closure-time (CT)-ADP) in the monitoring of immediate PA. This study examined whether CT-ADP could detect PAVR at 30 days and bleeding complications following TAVR. Methods CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PAVR was defined as a circumferential extent of regurgitation greater than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the VARC-2 classification. Results Significant PAVR was diagnosed in 44/219 patients. Important reduction of CT-ADP could be found in patients without PAVR, contrasting with the lack of CT-ADP improvement in significant PAVR patients. By univariate analysis, a self-expendable valve, valve size ≥ 31 mm and CT-ADP > 180 s were associated with PAVR. By multivariate analysis, CT-ADP > 180 s (HR 5.1 95% CI (2.5–10.6); P 180 s, but not PAVR, was proven to be an independent predictor of major/life-threatening bleeding (HR 1.813 (1.014–3.241); P = 0.045) [ Table 1 , Fig. 1 ]). Conclusion Post-procedural CT-ADP > 180 s is an independent predictor of significant PAVR 30 days after TAVR and may independently contribute to major/life-threatening bleedings. Other parameters such LVEF should be taken into account in the interpretation of prolonged CT-ADP time following valve implantation.

Background Bedside diagnosis between Takotsubo syndrome (TTS) and ACS remains challenging and requires multimodal examinations. Because invasive procedures portend by themselves a sizeable ischemic and bleeding risk in this frail population, non-invasive criteria are warranted to enable early diagnosis. Methods and results A total of 1100 patients (TTS n = 314, STEMI n = 452, NSTEMI n = 334) were enrolled in two centers. Baseline clinical and biological characteristics were compared between groups. At admission, cut-off values of BNP/TnI ratio of 54 and 329 distinguished respectively STEMI from NSTEMI, and NSTEMI from TTS. Best differentiation between TTS and ACS was obtained by the use of BNP/TnI ratio at peak (cut of value of 6 discriminated STEMI from NSTEMI, and 115 distinguished NSTEMI from TTS). We developed a score including 5 routinely available parameters (age, gender, history of psychiatric disorders, LVEF and BNP/TnI ratio on admission) enabling good distinction between TTS and STEMI 77% specificity and 92% sensitivity, AUC 0.93 (95% CI 0.92–0.95). For the distinction between TTS and NSTEMI, a second 4 variables score (gender, history of psychiatric disorders, LVEF on admission, BNP on admission) achieved a good diagnostic performance Se 89%, Sp 85%, AUC 0.94 (95% CI 0.92-0.96) ( Table 1 ). Conclusion A distinctive cardiac biomarker profile exists during TTS enabling at an early stage the differentiation between TTS and various myocardial infarction patterns. Best discrimination between TTS and ACS was obtained using a 4 (NSTEMI) or 5 variables score (STEMI).

Background Although the relationship between malignancies and catecholamine-induced myocardial stunning remains largely speculative, it has been suggested that the presence of cancer may lower the threshold for stress stimuli and/or may aggravate cardiac adrenoreceptor sensitivity. We sought to investigate whether associations exist between a previous or current diagnosis of malignancy, diagnostic parameters during hospitalization and death in takotsubo. Methods and results The 154 takotsubo patients were retrospectively identified between May 2008 and December 2014. Previous history of malignancy was identified in 44 patients (28.5%). Cardiac arrest was present at admission in 13 patients (8.4%). Intra-aortic balloon pump was inserted in 16 patients (10.4%). In patients with malignancy, higher B-type natriuretic peptide (BNP), leukocyte and C-reactive protein (CRP) peaks could be observed during the hospital phase. Initial impairment of left ventricular ejection fraction was negatively related to BNP, leukocyte, and CRP peaks. At a median follow-up of 364 days, all-cause death occurred in 41 patients (26.6%) and cardiac death in 12 patients (7.7%). Multivariate Cox regression analysis identified malignancy (hazard ratio 4.77 (1.02-22.17), leukocyte peak and age as independent predictors of cardiac death. Malignancy (2.62 (1.26-5.44), leukocyte peak (1.05 (1.01-1.08) and initial cardiac arrest (6.68 (2.47-18.01) were identified as independent predictors of overall mortality. Conclusions In the present takotsubo patients, the prevalence of malignancy was high and may have affected cardiovascular outcomes through the activation of inflammatory and neurohormonal mechanisms. (Circ J 2016; 80: 2192-2198).

Background: Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature EC aging and thrombogenicity. Methods: Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=4) by sequential centrifugation. The level of endothelial senescence was assessed as senescence-associated β-galactosidase activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, tissue factor activity using an enzymatic Tenase assay, the level of target protein expression by Western blot analysis, platelet aggregation using an aggregometer, and shear stress using a cone-and-plate viscometer. Results: Senescence, as assessed by senescence-associated β-galactosidase activity, was induced by the passaging of porcine coronary artery ECs from passage P1 to P4, and was associated with a progressive shedding of procoagulant MPs. Exposure of P1 ECs to MPs shed from senescent P3 cells or circulating MPs from ACS patients induced increased senescence-associated β-galactosidase activity, oxidative stress, early phosphorylation of mitogen-activated protein kinases and Akt, and upregulation of p53, p21, and p16. Ex vivo, the prosenescent effect of circulating MPs from ACS patients was evidenced only under conditions of low shear stress. Depletion of endothelial-derived MPs from ACS patients reduced the induction of senescence. Prosenescent MPs promoted EC thrombogenicity through tissue factor upregulation, shedding of procoagulant MPs, endothelial nitric oxide synthase downregulation, and reduced nitric oxide–mediated inhibition of platelet aggregation. These MPs exhibited angiotensin-converting enzyme activity and upregulated AT1 receptors and angiotensin-converting enzyme in P1 ECs. Losartan, an AT1 receptor antagonist, and inhibitors of either mitogen-activated protein kinases or phosphoinositide 3-kinase prevented the MP-induced endothelial senescence. Conclusions: These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II–induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt. They further suggest that targeting endothelial-derived MP shedding and their bioactivity may be a promising therapeutic strategy to limit the development of an endothelial dysfunction post-ACS.

The Ultraseal device (Cardia Inc., Eagan, MN) is a new left atrial appendage closure (LAAC) device, with a distal bulb and a proximal sail, connected by an articulating joint. We evaluated the feasibility, safety and efficacy of the Ultraseal device for LAAC in patients with nonvalvular atrial

Objectives The aim of this study was to investigate the respective impact of opiods analgesia and inhalation sedation with a 50% nitrous oxide/oxygen premix (Kalinox) on pain and occurence of radial artery spasm (RAS) during transradial coronary procedures. Backgroud With respect to the transfemoral approach, transradial procedures enable a drastic reduction of bleeding events and are associated with a reduction of mortality. RAS is one of the most common complications and may lead to patient discomfort and procedural failure. Currently, there is no consensus on the optimal sedation protocol to avoid RAS. Methods Consecutive patients undergoing transradial coronary angiography were prospectively enrolled in one single center study (Nouvel Hopital Civil, Strasbourg, France). Patients were allocated to opioids analgesia or inhalation sedation with Kalinox. The primary endpoints of the study were the incidence of a pain scale more than or equal to 5 and the occurrence of RAS. The secondary endpoint included the occurrence of side effects including nausea, vomiting, dizziness or faintness and headache. Results From September 2016 to February 2017 a total of 325 patients were enrolled (Opiods Analgesia n = 185, Kalinox n = 140). RAS and Pain scale ≥ 5 rates were not significantly differents in Opiods Analgesia and Kalinox groups (respectively 13.5% vs. 10% and 16.2% vs. 11.4%). Headache was more frequently observed in the kalinox group (6.4% vs. 0%; P = 0.002). By multivariate analysis, female gender, BMI Conclusion Procedural inhalation sedation by Kalinox is as safe as Opiods Analgesia during transradial coronary angiography.

Background Atrial arrhythmias (AA) are observed frequently early after lung transplant and also late after the surgery. Several predictive factors of post-operative AA after lung transplant have been already identified whereas those of late AA are still not known. Whether AA after lung transplant impacts mortality and the optimal strategy of rhythm management are still debated. The Purpose of the study was to assess in a large cohort of lung transplanted patients the incidence of AA early and late after surgery, their predictive factors and their impact on mortality. Methods and results We included 271 consecutive patients single or double lung-transplanted over a 9-years period in a large French center. We collected baseline clinical, surgery and post-operative data. The follow-up was 2,9±2,4 years. 33% patients developed post-operative AA. Age (HR=2,35; CI [1,31-4,24]) and chronic obstructive pulmonary disease (HR=1,028; CI [1,12-4,03]) were independant predictive factors of post-operative AA. Late AA occurred 2,2±2,7 years after transplant in 8.8% of the patients. Systolic pulmonary arterial pressure was the only independent predictive factor of late AA (HR=1,028; CI [1,001; 1,056]). Double lung transplant was associated with long term freedom from AF compared with single transplant (p=0,05) whereas the Kaplan-Meier curve for the development of late atrial flutter was similar in single and double lung transplant. Early and late AA after surgery showed no impact on mortality. Bilateral lung transplant was associated with a better survival. Conclusion Post-operative AA after lung transplantation are common with good outcome and contrast with the low occurrence of late organized AA. Double lung transplantation protects against AF but not AFL. Underlying electrophysiological mechanisms may explain these observations. Predictive factors of early and late AA after transplantation are different. Nevertheless these AA do not impact mortality after lung transplant (figure next page). Download : Download high-res image (108KB) Download : Download full-size image Abstract 0376 – Figure: Survival free of late AF and AFL by transplant

Background fragmented QRS complex (fQRS) is a marker of myocardial scarring and has prognostic significance. ST-segment resolution (STR) in STsegment elevation acute myocardial infarction (STEMI) is characteristic of tissue reperfusion. This study investigates the relationship between fQRS and STR in STEMI patients undergoing primary percutaneous coronary intervention (PCI) and determines the predictors of fQRS. Methods we analyzed the electrocardiograms (ECGs) of 256 patients included in a multicenter prospective STEMI-PCI study. fQRS and STsegment resolution were evaluated upon arrival in the ambulance (ECG-amb) and 1 h post-PCI (ECG-post). Major clinical cardiac events were assessed at 30 days and 6 months. Results fQRS was present in 33 patients (13.6%) on ECG-amb and in 30 patients (12%) on ECG-post. The presence of fQRS at either time was not associated with STR or clinical outcomes. In a multivariable analysis, the independent predictors of fQRS on ECG-amb were female sex (p=0.04), cardiac troponin Ic level at 72 h (p=0.01), TIMI 0-1 flow rate pre-PCI (p=0.002), and inferior STEMI location (p=0.04). Patients with fQRS on ECG-amb presented a larger necrosed mass on cardiac MRI than patients without fQRS (p=0.04). No predictors of fQRS post-PCI were identified. Conclusion the presence of fQRS at the time of presentation or 1 h after PCI was not associated with STR. However, fQRS was related to enzymatic infarct size, inferior STEMI location, and low TIMI flow rate.

Introduction ACS diagnosis relies on the detection of an increase or a decrease in troponin levels (delta-TnI) that might be estimated as absolute (delta-TnI-abs) or relative value (delta-TnI-rel). The discriminative cut-off value of delta-TnI to identify ACS in patients admitted in ICU is a matter of debate. Methods We aimed to determine in a monocentric registry the cut-off value of delta-TnI to identify ACS among patients admitted in ICU with a suspicion of acute myocardial ischemia. All the patients had 2 measurements of ultrasensible cTnI (ADVIA Centaur Siemens®; 99th percentile: 0,04 μg/L). Patients were classified in 4 groups: 1) ACS (NSTEMI, UA), 2) Cardiac non coronary diseases (heart failure, PE, arrhythmia, pericarditis, myocarditis, syncope, Tako-Tsubo), 3) Non cardiac diseases (pneumonia, stroke, epilepsy, neoplasm), 4) Chest pain of unknown origin (musculo-skelettal pain…) Results 275 patients were included. Medians of delta-TnI-abs were 0.12 [0 ; 1.01] ; 0.01 [0 ; 0.03] ; 0 [-0.01 ; 0] et 0 [0 ; 0] μg/L in groups 1 to 4 respectively. Medians of delta-TnI-rel) were 104 [0 ; 680] ; 2 [0 ; 62] ; 0 [-6 ; 0] et 0 [0 ; 0] % in groups 1 to 4 respectively. The delta-TnI-abs was significantly different between groups 1 and 2 (p=0.026). ROC curve analysis showed that optimal threshold of delta-TnI-abs was 0.02 μg/L (sensitivity 67%, specificity 76%) to distinguish group 1 from groups 2, 3 and 4. The threshold was 0.04 μg/L (sensitivity 61%, specificity 80%) to distinguish group 1 from group 2. The use of delta-TnI-rel yielded similar results and the only confounder was age. Conclusion This study suggests that the cut-off of delta-TnI to identify ACS in ICU patients should be higher to be discriminative of cardiac non coronary diseases. The identification of type 1 and type 2 myocardial infarction is a major challenge and needs further research.

Purpose Conduction disorders are frequent after transcatheter aortic valve implantation (TAVI). The aim of the study was to assess the incidence, the clinical impact and the predictive factors of new-onset left bundle branch block (LBBB) after TAVI. Methods Between 2010 and 2014, 198 consecutive patients underwent TAVI in our center and 156 were prospectively followed during 1 year (62 CoreValve (CV), 94 Edwards Sapiens valve (ES)). 42 patients were excluded because of a pre-existing PM before TAVI, death or surgery after TAVI. Results After 156 TAVI, 40 patients (26%) required pacemaker implantation. CV patients were more frequently implanted than ES (35% vs 19%; p=0.03). Out of 116 non-implanted patients, 53 (46%) patients presented with LBBB which persisted in 35 (30%) patients. QRS width increased +27ms in post-procedure, +21ms at hospital discharge, +15ms at 1 month, +11ms at 1 year in the whole cohort. There was no clinical nor echocardiographic difference between the LBBB group and no-LBBB group. Ischemic neurological complication were more frequent during hospitalization in the LBBB group (8.6% vs 3.7%; p=0.007). On multivariate analysis, a pre-existing incomplete LBBB (OR 4.15; IC 1.31-13.11; p=0.015) and a long pre-procedure PR interval (OR 1.023; IC 1.001-1.046; p=0.038) were predictive factors of new persistent LBBB after TAVI and a trend with CV implantation was observed (OR 2.35; IC 0.99- 5.53; p=0.051). NYHA grade was increased in the LBBB group compared to non-LBBB group at 1 (2,1 ± 0,8 vs 1,7 ± 0,6 ; p=0.006), 6 (2,21 ± 0,7 vs 1,53±0,6 ; p=0.001) and 12 months (2.2 vs 1.7, p=0.04). On univariate analysis, a pre-existing atrial fibrillation (OR 2.1; IC 1.12- 4.01; p=0.021), an initial mean aortic gradient (OR 0.78; IC 0.65-0.93; p=0.006) and new LBBB after TAVI (OR 2.06; IC 1.05-4.04; p=0.036) were predictive factors of mortality at 12 months. On multivariate analysis, LBBB after TAVI was an independent predictor of mortality (OR 3.52; IC 1.17- 10.58, p=0.025). Conclusion New-onset LBBB is frequent after TAVI and persists in a great proportion of patients. In our study, LBBB after TAVI was an independent predictor of mortality.

Purpose Atrioventricular (AV) conduction disturbance leading to pacemaker (PM) implantation is frequent after transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the incidence and the predictors of PM implantation after TAVI. Methods Between 2010 and 2014, 198 consecutive patients underwent TAVI in our center. 42 patients were excluded from the study because of a pre-existing PM before TAVI. 156 patients (62 Corevalve (CV), 94 Edwards Sapiens valve (ES) were included and prospectively followed during 1 year. Results Complete AV block occurred after TAVI in 29 patients (19%), second degree AV block in 3 (0.05%), new left bundle branch block (LBBB) in 53 (34%). A PM was implanted in 40 patients (26%). CV patients were more frequently implanted than ES (35% vs 19%; p=0.03). Post-procedure PR, QRS duration were longer in the PM group (227 vs 196ms; 159 vs 129ms, respectively, p Conclusion TAVI is associated in a great proportion of patients with AV disturbances which are mostly regressive over time. Patients with pre-existing RBBB, LBBB and high prosthesis/annulus diameter ratio are at increased risk of complete AV block. LVEF increase was lower in PM group even with a low percentage of stimulation time.

BackgroundAortic regurgitation (AR) after TAVI is the main limitation of this procedure. The aim of this study was to evaluate i) aortic annulus sizing by CT and/or echocardiography (TTE or TEE) ii) the incidence of AR and its determinism iii) the prognostic impact of AR and other survival predictors.Methods136 consecutive patients undergoing TAVI were included between 2010 and 2013. The aortic annulus sizing for prosthesis choice was done by TEE in 29 patients and by CT in 107 patients. Aortic valve calcium volume was measured by the volume technique in 67% of patients who have got CT. Follow-up was performed at 1, 6, 12 and 24 months.ResultsAortic annulus sizing by TTE and TEE echocardiography (TEE) were well correlated (r=0,73, p=0,0001, n=51) but were significantly lower than CT sizing (p < 0,0001). The incidence of AR ≥ 2/4 was 13% and was not significantly different according to the strategy of aortic annulus sizing for prosthesis choice. No predictor of AR≥ 2/4 was identified. Calcium volume was not associated either with AR with 1 month mortality. Mortality was 13% at 1 month, 25% at 1 year and 39% at 2 years. Predictors of mortality at 2years in univariate analysis were Euroscore> 25%, aortic regurgitation ≥ 2/4, renal failure with creatinin> 130μmol/l, anemia after TAVI < 8g/dl, trans aortic gradient before TAVI < 30mmHg and tamponade. In multivariate analysis, independent predictors were aortic regurgitation ≥ 2/4, anemia after TAVI < 8g/dl and tamponade (OR 2,75 CI 1,3-6,7; OR 2,5 CI 1,1-5,75 et OR 4,5 CI 1,30-15,55 respectively).ConclusionThis study showed that aortic annulus sizing by echocardiography is significantly lower than sizing by CT. AR have an independent prognostic on survival. Prevention of aortic regurgitation is an important issue for the future of this technique.

Background Cardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation. Methods The study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared. Results The mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03–6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status. Conclusions KT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.

IntroductionThe PARTNER trial has shown that TAVI is not inferior to surgical aortic valve replacement (AVR) in high-risk aortic stenosis. However, real life registry comparing TAVI and surgery are lacking.Methodsmonocentric registry of high-risk patients (lEUROSCORE1 ≥15%) undergoing TAVI (114 patients) or AVR (81 patients) between 2009 and 2013 in our institution.ResultsMean age was 84,4 and 83,6 yo (p=NS). TAVI patients had higher EUROSCORE1 (31 vs 24.5%, p