The Paradox of Pulmonary Vascular Resistance: Restoration of Pulmonary Capillary Recruitment as a Sine Qua Non for True Therapeutic Success in Pulmonary Arterial Hypertension.

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.

Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease.

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 < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05). 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).

Impact of Opioid Analgesia and Inhalation Sedation Kalinox on Pain and Radial Artery Spasm during Transradial Coronary Angiography.

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 Hôpital 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 ≥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 ≥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 <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.

Frailty and Bleeding in Older Adults Undergoing TAVR or SAVR: Insights From the FRAILTY-AVR Study.

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.

Left ventricular mechanics in the acute phase of Takotsubo cardiomyopathy: distinctive ballooning patterns translate into different diastolic properties.

Although apical and midventricular Takotsubo cardiomyopathies (TTCs) share common triggers and pathophysiological features, little is known about the potential differences in left ventricular (LV) mechanistic properties between these TTC phenotypes. We sought to investigate whether LV systolic and/or diastolic function, as assessed invasively by left heart catheterization (LHC), differ according to ballooning patterns in the acute phase of TTC. One hundred and fourteen TTC patients were retrospectively identified between January 2009 and December 2015 at the University Hospital of Strasbourg, France. A comprehensive list of LV quantitative parameters was derived from LHC analysis for each patient. We examined 2 groups of patients according to ballooning patterns in the acute phase of TTC: patients with apical ballooning ("Apical group"; n = 76) and those with midventricular ballooning ("Midventricular group"; n = 38). LV minimal diastolic pressure (8.72 ± 6.72 vs. 5.02 ± 6.08 mmHg; p = 0.004), LV end diastolic pressure (23.11 ± 8.32 vs. 18.84 ± 8.06 mmHg; p = 0.01), and LV diastolic stiffness (LV stiffness 1: 0.29 ± 0.23 vs. 18.84 ± 8.06 mmHg/mL; p = 0.04-LV stiffness 2: 0.16 ± 0.08 vs. 0.12 ± 0.05 mmHg/mL; p = 0.005) were significantly higher in patients with apical TTC than in the midventricular group. Concomitantly, these findings were associated with significantly higher BNP levels in the apical group (923.91 ± 1164.53 vs. 418.71 ± 557.75 pg/mL; p = 0.004) than in the midventricular group. In the acute phase of stress cardiomyopathy, the classic apical form of TTC is associated with poorer diastolic function compared to the midventricular ballooning variant, as assessed through direct invasive hemodynamic measurements using LHC.

Atrial arrhythmias in Takotsubo cardiomyopathy: incidence, predictive factors, and prognosis.

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.

Does Transcatheter Aortic Valve Replacement Modulate the Kinetic of Superoxide Anion Generation?

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 vs. 0.648 ± 0.193; p < 0.001) and persistent at 3 days (0.611 ± 0.0.228 vs. 0.646 ± 0.199; p = 0.033) and 30 days follow-up (0.572 ± 0.207 vs. 0.639 ± 0.199; p = 0.005). Increased baseline SA (>75 percentile) was continuously associated with higher postprocedural SA values 10 min after valve expansion (p < 0.001), at 3 days (p < 0.001) and 30 days (p < 0.001). Higher baseline SA was linked to higher inflammatory response assessed by higher C-reactive protein values at day 1 and day 3. The composite endpoint of all-cause mortality and/or stroke and/or pacemaker implantation and/or significant paravalvular aortic regurgitation ≥mild at 30 days did not differ significantly according to SA baseline values (p = 0.055). This is the first report identifying a decrease in oxidative stress level after TAVR. Our observation leads to the hypothesis that oxidative stress biomarkers may survive the journey from bench to bedside in AS and TAVR and become new biomarkers with both diagnostic and prognostic values. Antioxid. Redox Signal. 31, 420-426.

Primary Hemostatic Disorders and Late Major Bleeding After Transcatheter Aortic Valve Replacement.

BACKGROUND: Periprocedural and late (>30 days) bleedings represent major complications after transcatheter aortic valve replacement and have been identified as potential areas for improved patient care. OBJECTIVES: The authors sought to evaluate the impact of ongoing primary hemostasis disorders on late major/life-threatening bleeding complications (MLBCs). METHODS: Bleedings were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Closure time of adenosine diphosphate (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: Among 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 (42.8%) and were associated with increased overall mortality (hazard ratio [HR]: 5.66; 95% confidence interval [CI]: 3.10 to 10.31; p < 0.001) and cardiac mortality (HR: 11.62; 95% CI: 4.59 to 29.37; p < 0.001). A 2.5-fold elevation of MLBCs could be evidenced in patients with a CT-ADP > 180 s (27.4% vs. 11.5%; p < 0.001). Multivariate regression analysis identified paravalvular leak (PVL) (HR: 6.31; 95% CI: 3.43 to 11.60; p < 0.0001) and CT-ADP > 180 s (HR: 3.08; 95% CI: 1.62 to 5.81; p = 0.0005) as predictor of MLBCs. CONCLUSIONS: MLBCs after transcatheter aortic valve replacement are frequent and associated with an increased morbidity and mortality. PVL and CT-ADP >180 s were identified as strong predictors for MLBCs. These findings strongly suggest that persistent HMW defects contribute to enhanced bleeding risk in patients with residual PVL.

Percutaneous Left Atrial Appendage Closure With the Ultraseal Device: Insights From the Initial Multicenter Experience.

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.

Ventricular arrhythmias and sudden cardiac arrest in Takotsubo cardiomyopathy: Incidence, predictive factors, and clinical implications.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is a stress-related transient cardiomyopathy. Life-threatening arrhythmias (LTA) can occur and worsen prognosis. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 duration >105 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. CONCLUSION: LTAs occur early in patients presenting with TTC and are associated with significantly worse short- and long-term prognosis. Left ventricular impairment and QRS duration >105 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.

CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and Bleeding Events following Transcatheter Aortic Valve Replacement.

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 < 0.001) and a self-expandable valve were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural CT-ADP >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.

The Amplatzer Amulet Device: Technical Considerations and Procedural Approach.

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.

Antiplatelet Therapy in ACS Patients: Comparing Appropriate P2Y12 Inhibition by Clopidogrel to the Use of New P2Y12 Inhibitors.

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 long-term 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.

Unexpected Problems of Antithrombotic Therapy with An Unusual Side Effect of Vitamin K Antagonists after Mitral Valve Replacement.

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.

Pharmacogenetics of Lipid-Lowering Agents: an Update Review on Genotype-Dependent Effects of HDL-Targetingand Statin Therapies.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

Out-of-hospital cardiac arrest survivors sent for emergency angiography: a clinical score for predicting acute myocardial infarction.

BACKGROUND: 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. METHODS: Consecutive OHCA patients who underwent emergency coronary angiography in our centre between 2009 and 2013 were included in this retrospective single-centre observational study. RESULTS: 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. CONCLUSIONS: 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.

Early and Late Atrial Arrhythmias After Lung Transplantation　- Incidence, Predictive Factors and Impact on Mortality.

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.

Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

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 ß-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 ß-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 ß-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.