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Background The diagnosis of pulmonary arterial hypertension requires right heart catheterization (RHC) which is typically performed via proximal venous access (PVA). Antecubital venous access (AVA) is an alternative approach for RHC that can minimize complications, decrease procedural duration and allow for immediate patient recovery. A direct comparison between the two procedures in patients with pulmonary hypertension (PH) is lacking. Objectives To determine the feasibility, safety, and adoption rates of AVA-RHC as compared with ultrasound-guided PVA in a subpopulation of patients with PH. Methods All patients who underwent RHC for evaluation of PH between December 2014 and March 2017 at a single large academic medical center were included in this study. Demographic, procedural and outcomes data were retrieved from the medical records. Results In total, 159 RHC were included (124 AVA, 35 PVA). The duration of RHC was significantly shorter in the AVA compared with PVA group (53 (IQR 38–70) vs. 80 (IQR 56–95) min, respectively, p

The standard approach for urgent trans-venous temporary cardiac pacemaker (TVTP) implantation is fluoroscopy guidance. The delay in activation of the fluoroscopy-room and the transfer of unstable patients may be life-threatening. Echocardiography-guided TP implantation may increase the safety of the patients by obviating the need for in-hospital transfer. We examined the feasibility and safety of echocardiography-guided vs. fluoroscopy-guided TVTP implantation. From January 2015 to September 2017 data for consecutive patients who needed emergent TVTP implantation were retrospectively reviewed. Ultrasound-guided TVTP protocol that was introduced in our center in January 2015 involved ultrasound guidance for both central venous access and pacing lead positioning. Access sites included femoral, subclavian, or jugular veins. Electrodes were placed in the right ventricular apex by means of echocardiographic monitoring in intensive care unit or by fluoroscopic guidance. Endpoints were achievement of successful ventricular pacing and procedural complications. Sixty-six patients (17 echocardiography-guided and 49 fluoroscopy-guided) were included. There were no differences in pacing threshold between the echocardiography-guided group and the fluoroscopy-guided group (0.75 ± 0.58 mA vs. 0.57 ± 0.35 mA, p = 0.24). The access site for implantation was femoral vein in 27% for the fluoroscopy-guided vs. none for the echocardiography-guided approach (p = 0.015). One hematoma and one related infection occurred in the fluoroscopy-guided group. The need for electrode repositioning was observed in 1 patient in each group. There were no procedural-related deaths in either group. Echocardiography-guided temporary cardiac pacing is a feasible and safe alternative to fluoroscopy-guided approach and significantly lowers the need for in-hospital transfer.

Essentials Exercise Limitation 1 year after an acute pulmonary embolism is common.Serial imaging after acute pulmonary embolism is not well described and how it affects exercise limitation remains unknown.1 year after an acute pulmonary embolism chronic changes are common, more so on perfusion lung scanning than CT pulmonary angiography, but imaging findings did not predict exercise limitation. Introduction Risk factors for exercise limitation after acute pulmonary embolism (PE) are unknown. As a planned sub‐study of the prospective, multicenter ELOPE (Evaluation of Long‐term Outcomes after PE) Study, we aimed to describe the results of serial imaging by computed tomography pulmonary angiography (CTPA) and perfusion scan during 1 year after a first episode of acute pulmonary embolism, and to assess the association between imaging parameters and exercise limitation at 1 year. Methods In a prospective cohort study, 100 patients were recruited between June 2010 and February 2013 at five Canadian university–affiliated hospitals. CT pulmonary angiography was performed at baseline and 12 months, perfusion scan at 6 and 12 months, and cardio‐pulmonary exercise testing at 1 and 12 months. Imaging parameters included: on CT pulmonary angiography, CT obstruction index (CTO) (% clot burden in the pulmonary vasculature), and on perfusion scan, pulmonary vascular obstruction (PVO) (% perfusion defect). Abnormal cardio‐pulmonary exercise test (primary outcome) was defined as percent of predicted peak oxygen uptake (VO2) 80% on 1‐year cardio‐pulmonary exercise testing (1.4% [0%; 5.7%] vs 1.0% [0%; 2.4%]; P = .70). Mean (SD) pulmonary vascular obstruction at 6 and at 12 months was similar in patients with percent‐predicted VO2 peak 80% (6 months: 5.9% [0%; 10.4%] vs 6.2% [4.5%; 9.0%]; P = .91; 12 months: 5.1% [0%; 10.2%] vs 6.0% [0%; 9.7%]; P = .71). Conclusions Imaging findings after pulmonary embolism did not predict exercise limitation. Residual thrombus does not appear to explain long‐term functional limitation after pulmonary embolism.

Treatment delays in patients with acute myocardial infarction (AMI) are related to increased morbidity and mortality. Hence, identifying determinants of delay may help reduce time to treatment. Importantly, limited data suggest that there may be sex-related disparities in benchmark timelines. Although guidelines advocate the use of the first medical contact (FMC) rather than hospital admission as the moment from which delays to treatment should be monitored, the latter is still often used for quality purposes. We aimed to identify factors associated with treatment delays, with an emphasis on sex-related disparities. We reviewed data on 3,658 patients with AMI from 2 contemporary, consecutive multicenter surveys. Measured delays were FMC-to-electrocardiogram >10 minutes in ST-elevation MI (STEMI) and non-STEMI, FMC-to-primary percutaneous coronary intervention >90 minutes in STEMI, and invasive angiography >72 hours after admission in non-STEMI patients. Timely electrocardiogram was performed in 48% of patients with STEMI and in 39.8% of non-STEMI patients without significant sex-related differences. Independent determinants of delay included atypical chest pain (CP) and presentation during daytime. In patients with STEMI, 37.5% had primary percutaneous coronary intervention in less than 90 minutes without significant sex-related disparities. Independent determinants of delay included atypical CP, night presentation, and diabetes. In non-STEMI patients, independent determinants of delayed invasive approach were female sex, age >75 years, atypical CP, and renal failure. In conclusion, significant treatment delays in patients with AMI are still frequent in contemporary practice, highlighting the need for improvement and guidelines implementation. Predictors of delay identified in our study may facilitate targeting of interventions to improve adherence to guidelines.

International audience; Acute cardiovascular care has progressed considerably since the last position paper was published 10 years ago. It is now a well-defined, complex field with demanding multidisciplinary teamworking. The Acute Cardiovascular Care Association has provided this update of the 2005 position paper on acute cardiovascular care organisation, using a multinational working group. The patient population has changed, and intensive cardiovascular care units now manage a large range of conditions from those simply requiring specialised monitoring, to critical cardiovascular diseases with associated multi-organ failure. To describe better intensive cardiovascular care units case mix, acuity of care has been divided into three levels, and then defining intensive cardiovascular care unit functional organisation. For each level of intensive cardiovascular care unit, this document presents the aims of the units, the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region/area. This update emphasises cardiologist training, referring to the recently updated Acute Cardiovascular Care Association core curriculum on acute cardiovascular care. The training of nurses in acute cardiovascular care is additionally addressed. Intensive cardiovascular care unit expertise is not limited to within the unit's geographical boundaries, extending to different specialties and subspecialties of cardiology and other specialties in order to optimally manage the wide scope of acute cardiovascular conditions in frequently highly complex patients. This position paper therefore addresses the need for the inclusion of acute cardiac care and intensive cardiovascular care units within a hospital network, linking university medical centres, large community hospitals, and smaller hospitals with more limited capabilities.

Background We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea. Methods One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (Vo2 peak) Results At 1 year, 40 of 86 patients (46.5%) had percent predicted Vo2 peak Conclusions Almost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE. Trial Registry ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov.

Limited data are available regarding the optimal management of patients with cancer in the acute myocardial infarction (AMI) setting.We studied consecutive patients with AMI included in a national registry (years 2010, 2016) with the diagnosis of past or active malignancy and followed them for 1 year.Our cohort consisted of 2937 cancer-naive patients and 152 patients with cancer, of whom 35% presented with active malignancies. Compared with cancer-naive patients, patients with cancer were older, with female predominance, and presented more often with a history of hypertension and chronic kidney disease (P0.001 for all comparisons). The rate of ST-elevation AMI was comparable (P=0.067). GRACE score more than 140 was more common in the cancer group (P0.001). Most patients with cancer were referred to coronary angiography, though less than cancer-naive patients (87 vs. 93%; P=0.004). The rate of percutaneous coronary intervention was similar (P=0.265). Propensity score matching demonstrated similar rates of in-hospital complications between groups, and no mortality or major cardiac adverse event differences were noted at 30 days. Moreover, short-term mortality was similar between patients with active versus past malignancies, and between patients with solid and nonsolid tumors. However, cancer in patients with AMI was found to predict an increased mortality risk at 1 year by multivariable analysis (hazard ratio=2.52; P0.001).Patients with cancer and AMI have a more complicated clinical presentation, yet their short-term prognosis is similar to cancer-naive patients. Nevertheless, 1-year outcome is worse.

Atrial fibrillation (AF) is highly prevalent in dialysis patients, however whether its impact differs between patients on haemodialysis (HD) vs. peritoneal dialysis (PD) is unknown. We aimed to compare the association of AF and clinical outcomes in different dialysis modalities. We performed a population based retrospective cohort study, including adult patients who initiated dialysis between the years 2002 and 2015. Clinical, echocardiographic and laboratory data were reviewed and correlated with outcomes in HD vs. PD. During the study period, 1,130 patients began dialysis. Of the 997 patients without AF before dialysis initiation, 17% developed new-onset AF after the initiation of dialysis (17.3% of HD vs. 13.7% of PD patients, p = 0.27). Using multivariate analysis, only enlarged left atrium at dialysis initiation (hazard ratio (HR) 2.82, CI95% 2.00–3.99) and age (HR 1.04, CI95% 1.03–1.06) were significantly associated with AF. Dialysis modality was not a significant predictor of AF in either univariate or multivariate analysis. In conclusion, our study demonstrated that AF is common in dialysis patients irrespective of modality. In our cohort, the risk factors associated with AF were older age and enlarged left atrium. AF was associated with increased rates of heart failure and mortality, but not stroke.

Prasugrel has proved its superiority over clopidogrel for reducing ischemic events among patients with ST elevation myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). Data on switching of antiplatelet therapy in acute coronary syndrome patients in clinical practice are very limited. Importantly, the safety of in-hospital switching from clopidogrel to prasugrel following thrombolysis has not been addressed.We reviewed consecutive STEMI patients from February 2011 to April 2014 who were transferred to a tertiary center after receiving thrombolysis and a loading dose of clopidogrel in a non-PCI-capable center. If not contraindicated, these patients were reloaded and treated with prasugrel. A control group, three times larger, was selected from patients who underwent primary PCI and were initially treated with prasugrel. In-hospital outcomes were examined.Cases (n=45, 13% female, mean age 56 years) and controls (n=135, 11% female, mean age 54 years) did not differ significantly with respect to MI location, left ventricular systolic function, and extent of coronary artery disease. Mean time from thrombolysis to prasugrel loading was 32±19 hours. No significant differences were found between cases and controls in TIMI major or minor bleeding (0% vs. 3%), overall mortality (0% vs. 1.5%), and hospitalization length (4.8 vs. 5.5 days).In-hospital reloading and subsequent maintenance therapy with prasugrel in patients who received thrombolysis and a loading dose of clopidogrel appears to be as safe as in STEMI patients managed by primary PCI; however, larger studies are needed to verify these results.

Spasm of the left main coronary artery (LM) is considered to be rare. We investigated the angiographic characteristics of the LM in patients with combined LM and disease involving additional vessels, who underwent coronary artery bypass grafting (CABG) and underwent repeat coronary angiography within 5 years of the CABG, to examine the apparent frequency of spasm of the LM on initial angiography and its possible predictors. A retrospective analysis was performed of patients who underwent coronary angiography in our institute, who were found to have significant LM stenosis and disease involving additional vessels, underwent CABG and repeat coronary angiography within 5 years of the CABG. Data on angiographic characteristics of the LM on the initial angiogram were investigated. Of 84 patients, 17 (20%) were found to have a normal LM on repeat angiography (group A), and 67 (80%) demonstrated significant stenosis (group B). The degree of LM stenosis was milder in the initial angiogram in group A than in group B (64 ± 15% vs 72 ± 14%, p = 0.047). Most patients in group A demonstrated tubular LM stenosis at initial catheterization in comparison to group B (71% vs 18%). Using multivariate analysis, the only predictor for a normal LM at repeat catheterization was found to be tubular stenosis at initial catheterization (odds ratio 123, 95% confidence interval 4.0 to 3696). In conclusion, LM coronary spasm is a common finding, particularly in those with the appearance of tubular stenosis, and it should be excluded even in patients with additional coronary disease in certain instances to prevent unnecessary CABG.

Premature myocardial infarction (MI) is an increasingly prevalent cause of morbidity and mortality worldwide. A subset of patients, predominantly young women, present with MI with no obstructive coronary artery disease (MINOCA), a nomenclature gaining recognition. However, few data exist on presentation and prognosis according to the severity of coronary artery disease (CAD).We studied patients with premature (younger than 55 years of age) acute MI enrolled in a large cohort in 24 centres across Canada. Baseline clinical, psychosocial, and coronary anatomy characteristics as well as 12-month outcomes were compared between patients with MINOCA (50% stenosis) and patients with MI with obstructive CAD (≥ 50% stenosis; MICAD).From a cohort of 1210 patients with acute coronary syndrome, we examined 998 MI patients with available angiography core lab readings: 82 (8.2%) had a MINOCA and 916 (91.8%) had a MICAD. Forty percent of patients with MINOCA were women compared with one-third with MICAD. The prevalence of traditional risk factors and chest pain at presentation was lower in MINOCA patients, yet 37% had a ST-elevation MI and 10% presented with a cardiac arrest. No evident etiology was detected in70% of MINOCA, but 10% presented with either spontaneous coronary dissection or Takotsubo cardiomyopathy. Although combined major adverse cardiovascular events and all-cause readmission rate was lower in the MINOCA group (14% vs 25%; adjusted hazard ratio, 0.51; 95% confidence interval, 0.28-0.93), it was not negligible.Patients with MINOCA present with high-risk features despite the absence of obstructive CAD. A search for etiology and eventual treatment provides a rich avenue for improving prognosis in young women with premature MI.

Background We aimed to evaluate health-related quality of life (QOL), dyspnea, and functional exercise capacity during the year following the diagnosis of a first episode of pulmonary embolism. Methods This was a prospective multicenter cohort study of 100 patients with acute pulmonary embolism recruited at 5 Canadian hospitals from 2010-2013. We measured the outcomes QOL (by Short-Form Health Survey-36 [SF-36] and Pulmonary Embolism Quality of Life [PEmb-QoL] measures), dyspnea (by the University of California San Diego Shortness of Breath Questionnaire [SOBQ]) and 6-minute walk distance at baseline and 1, 3, 6, and 12 months after acute pulmonary embolism. Computed tomography pulmonary angiography was performed at baseline, echocardiogram was performed within 10 days, and cardiopulmonary exercise testing was performed at 1 and 12 months. Predictors of change in QOL, dyspnea, and 6-minute walk distance were assessed by repeated-measures mixed-effects models analysis. Results Mean age was 50.0 years; 57% were male and 80% were treated as outpatients. Mean scores for all outcomes improved during 1-year follow-up: from baseline to 12 months, mean SF-36 physical component score improved by 8.8 points, SF-36 mental component score by 5.3 points, PEmb-QoL by −32.1 points, and SOBQ by −16.3 points, and 6-minute walk distance improved by 40 m. Independent predictors of reduced improvement over time were female sex, higher body mass index, and percent-predicted VO 2 peak Conclusions On average, QOL, dyspnea, and walking distance improve during the year after pulmonary embolism. However, a number of clinical and physiological predictors of reduced improvement over time were identified, most notably female sex, higher body mass index, and exercise limitation on 1-month cardiopulmonary exercise test. Our results provide new information on patient-relevant prognosis after pulmonary embolism.

Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care.We studied 1123 patients (18-55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures.Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non-ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework.Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.

Background The incidence of pericardial effusion (PEF) during long-term follow-up among patients with pulmonary arterial hypertension (PAH) is unknown. We aimed to determine the incidence and prognostic significance of developing a new PEF among PAH patients. Methods Records of consecutive patients diagnosed with PAH between January 1990 and May 2010 were reviewed. Patients had systematically undergone right heart catheterization, transthoracic echocardiography, and coronary angiography during their initial assessment as well as routine echocardiograms during follow-up. Effusions were graded as small (echo-free space in diastole Results The entire cohort consisted of 154 patients. The prevalence of identified PEF during initial assessment was 28.6%. The incidence of PEF among patients with no effusions who had additional echocardiographic studies during follow-up (n = 102) was 44.1%. Patients who developed PEF during follow-up had no differences with respect to baseline characteristics, associated aetiologies, hemodynamic parameters, and extent of coronary disease. Among these 102 patients, survival estimates were 94.9%, 75.0%, and 62.4% at 1, 3, and 5 years, respectively. Development of a PEF that was at least moderate-sized at its first appearance was a predictor of mortality in univariate (hazard ratio, 6.85; 95% confidence interval, 2.60-18.10) as well as multivariate analysis (hazard ratio, 3.95; 95% confidence interval, 1.26-12.40). Conclusions PEF develops frequently in PAH patients. In patients with no PEF at baseline, the appearance of a new moderate-size or larger PEF is associated with increased mortality, whereas no significantly increased mortality was observed when a small PEF develops.

Background— Although echocardiography is commonly performed before coronary artery bypass surgery, there has yet to be a study examining the incremental prognostic value of a complete echocardiogram. Methods and Results— Patients undergoing isolated coronary artery bypass surgery at 2 hospitals were divided into derivation and validation cohorts. A panel of quantitative echocardiographic parameters was measured. Clinical variables were extracted from the Society of Thoracic Surgeons database. The primary outcome was in-hospital mortality or major morbidity, and the secondary outcome was long-term all-cause mortality. The derivation cohort consisted of 667 patients with a mean age of 67.2±11.1 years and 22.8% females. The following echocardiographic parameters were found to be optimal predictors of mortality or major morbidity: severe diastolic dysfunction, as evidenced by restrictive filling (odds ratio, 2.96; 95% confidence interval, 1.59-5.49), right ventricular dysfunction, as evidenced by fractional area change 0.40 (odds ratio, 1.89; 95% confidence interval, 1.13-3.15). These results were confirmed in the validation cohort of 187 patients. When added to the Society of Thoracic Surgeons risk score, the echocardiographic parameters resulted in a net improvement in model discrimination and reclassification with a change in c-statistic from 0.68 to 0.73 and an integrated discrimination improvement of 5.9% (95% confidence interval, 2.8%-8.9%). In the Cox proportional hazards model, right ventricular dysfunction and pulmonary hypertension were independently predictive of mortality over 3.2 years of follow-up. Conclusions— Preoperative echocardiography, in particular right ventricular dysfunction and restrictive left ventricular filling, provides incremental prognostic value in identifying patients at higher risk of mortality or major morbidity after coronary artery bypass surgery.

Our study aimed to determine the prevalence of occult left-heart disease in patients with scleroderma and pulmonary hypertension. In patients with pulmonary hypertension (mean pulmonary artery pressure (mean PAP)≥25 mmHg), differentiation between pre- and post-capillary pulmonary hypertension has been made according to pulmonary artery wedge pressure (PAWP) less than or more than 15 mmHg, respectively. We performed a retrospective chart review of 107 scleroderma patients. All patients with suspected pulmonary hypertension had routine right or left heart catheterisation with left ventricular end-diastolic pressure (LVEDP) measurement pre-/post-fluid challenge. We extracted demographic, haemodynamic and echocardiographic data. Patients were classified into one of four groups: haemodynamically normal (mean PAP25 mmHg); pulmonary venous hypertension (PVH) (mean PAP≥25 mmHg, PAWP15 mmHg); occult PVH (mean PAP≥25 mmHg, PAWP≤15 mmHg, LVEDP15 mmHg before or after fluid challenge); and pulmonary arterial hypertension (PAH) (mean PAP≥25 mmHg, PAWP≤15 mmHg and LVEDP≤15 mmHg before or after fluid challenge). 53 out of 107 patients had pulmonary hypertension. Based on the PAWP-based definition, 29 out of 53 had PAH and 24 out of 53 had PVH. After considering the resting and post-fluid-challenge LVEDP, 11 PAH patients were reclassified as occult PVH. The occult PVH group was haemodynamically, echocardiographically and demographically closer to the PVH group than the PAH group. PVH had high prevalence in our scleroderma-pulmonary hypertension population. Distinguishing PAH from PVH with only PAWP may result in some PVH patients being misclassified as having PAH.

We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea.One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (VoAt 1 year, 40 of 86 patients (46.5%) had percent predicted VoAlmost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE.ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov.

Background Over past decades, the incidence of acute coronary syndrome (ACS) has increased in young women, and greater mortality rates after discharge were observed among young women vs men. We revisited this issue with contemporary data from the Gen d e r and S ex Determ i nant s of Cardiovascular Disease: From Bench to Beyond Pr emature A cute Coronary S y ndrome (GENESIS-PRAXY), a multicentre prospective cohort study. Methods One thousand two hundred thirteen patients were enrolled in GENESIS-PRAXY from 26 centres across Canada, the United States, and Switzerland between January 2009 and April 2013. We assessed major adverse cardiac events (MACE) and mortality over 12 months after ACS. The role of sex as a predictor of outcomes was determined with Cox proportional hazard regression analysis. Results We included 1163 patients with complete data. The occurrence of MACE was 9% and 8% in women and men, respectively ( P = 0.75), and 1% of women and men died during follow-up. In adjusted models, there was no sex difference in the risk of MACE or mortality. The proportion of patients with all-cause rehospitalization was higher in women (13%) compared with men (9%; P = 0.006), but cardiac rehospitalization rates were similar in both sexes regardless of ACS type. Among first rehospitalizations, the majority was classified as cardiac related (69%), with chest pain or angina (28%) and myocardial infarction (19%) reported as the most common reasons for first rehospitalization. Conclusions Women were more likely than men to be rehospitalized for all causes but not for a cardiac cause. In contrast to earlier studies, men and women had similar mortality and MACE outcomes at 1 year.

Background Combination therapy (CT) for patients with pulmonary arterial hypertension (PAH) has been recommended for many years, despite weak evidence of efficacy over monotherapy (MT). A previous meta-analysis comparing CT vs MT with pulmonary vasodilators failed to demonstrate a clear reduction in clinical worsening events. Methods We searched for relevant articles in PubMed, EMBASE, the Cochrane Database, and clinicaltrials.gov; we also manually searched review articles and conference abstracts from 1980-December 2015. Target articles were double-blinded studies of 2 or more pulmonary vasodilators given in combination vs monotherapy for treatment of patients with PAH. The principal outcome of interest was "combined clinical worsening" (CCW) events (including but not limited to death or hospitalization). Data on physiological outcomes were also explored. Meta-analysis was performed using the DerSimonian and Laird random-effects model. Results We extracted data from 18 randomized controlled trials (RCTs) (N = 4162). CT was associated with a significant 38% reduction of risk of CCW (15 RCTs: n = 3906; risk ratio [RR], 0.62; 95% confidence interval [CI], 0.50-0.77). This reduction in risk was driven by a reduction in nonfatal end points (12 RCTs: n = 2611; RR, 0.56; 95% CI, 0.40-0.78) and not by a reduction of mortality (12 RCTs: n = 2717; RR, 0.79; 95% CI, 0.53-1.17). CT was also associated with improvement in 6-minute walking distance (10 RCTs: n = 1553; weighted mean difference [WMD], +23.0 m; 95% CI, 15.9-30.1), improved functional class (9 RCTs: n = 1737; RR, 1.26; 95% CI, 1.05-1.51), and beneficial effects on pulmonary hemodynamics such as cardiac index (WMD, +0.35 L/min/m; 95% CI, 0.14-0.56). Conclusions In this highly comprehensive meta-analysis, CT reduces the risk of CCW events in patients with PAH and brings physiological improvement.

Recent registries describe a significant prevalence of pulmonary arterial hypertension (PAH) in the elderly, but little is known of their characteristics. We aimed to examine the features and prognostic factors of long-term survival in elderly (≥65 years) PAH patients. Clinical, echocardiographic, angiographic, hemodynamic, treatments, and survival data were reviewed in consecutive patients over the course of 20 years. Elderly PAH patients (n = 47) were compared to younger PAH patients (n = 107). At presentation, elderly patients were more likely to have hypertension, diabetes, dyslipidemia, coronary disease, and PAH associated with scleroderma (42.6 vs. 24.3 %; p = 0.02) than younger patients. Prior to PAH therapy, elderly patients had better right ventricular myocardial performance index (RV-MPI; 0.48 ± 0.20 vs. 0.62 ± 0.23, p = 0.006) and lower mean pulmonary arterial pressure (PAP; 45.0 ± 11.1 vs. 49.2 ± 11.8 mmHg, p = 0.04). Elderly patients were treated less often with epoprostenol (8.5 vs. 29 %, p = 0.006) or trepostinil (8.5 vs. 23.4 %, p = 0.04). The 1, 3, and 5 year survival rates of elderly patients were estimated to be 76.4, 50.5, and 37.6 %, respectively. In comparison, younger patients had survival estimates of 92.2, 74.2 and 64.0 % (p = 0.002). Baseline right atrial pressure, mean PAP, cardiac index, and RV-MPI were associated with survival in elderly patients; however in these patients, survival was not affected by any PAH subgroup or age (per year) by itself. The diagnosis of PAH in elderly patients is associated with poorer survival which is in part explained by a greater vulnerability to the hemodynamic disturbances of PAH.

New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.

It is unclear whether intracoronary (IC) bolus administration of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes is superior to intravenous (IV) administration. We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of IC and IV administrations of GPIs in patients with acute coronary syndromes. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for RCTs comparing IC to IV administration of GPIs (abciximab, eptifibatide, tirofiban) during PCI. Data were pooled and stratified into short (1 month to 3 months) and mid-/long-term (≥6 months) follow-up durations. Ten RCTs involving 1,590 patients met our inclusion criteria. Compared to the IV group the IC group was more likely to have complete perfusion (Thrombolysis In Myocardial Infarction grade 3 flow) after PCI (risk ratio [RR] 1.08, 95% confidence interval [CI] 1.02 to 1.15). IC administration was associated with similar bleeding rates as IV (RR 0.92, 95% CI 0.68 to 1.24) but with a significant decrease in short-term target vessel revascularization (RR 0.54, 95% CI 0.30 to 0.96). IC administration was also associated with a significant decrease in short-term mortality (RR 0.45, 95% CI 0.23 to 0.90) but this decrease was no longer significant in mid-/long-term RCTs. In conclusion, compared to IV administration IC administration of GPIs has favorable effects on Thrombolysis In Myocardial Infarction flow, target vessel revascularization, and short-term mortality after PCI, with no difference in rates of bleeding. Data regarding mid-/long-term outcomes were limited and inconclusive. Large RCTs with longer follow-up are required to determine long-term safety and efficacy.

Previous studies comparing combination therapy (CT) of pulmonary vasodilators to monotherapy (MT) in patients with pulmonary arterial hypertension (PAH) report conflicting results as to whether CT is more efficacious than MT. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials comparing CT to MT for patients with PAH. Data were pooled using the DerSimonian-Laird random-effects model. Six randomized controlled trials including 729 patients met our inclusion criteria. Follow-up ranged from 12 to 16 weeks. Compared to MT, CT resulted in a modest increase in 6-minute walk distance at the end of follow-up (weighted mean difference 25.2 m, 95% confidence interval [CI] 13.3 to 37.2). CT did not decrease mortality (risk ratio [RR] 0.42, 95% CI 0.08 to 2.25), admissions for worsening PAH (RR 0.72, 95% CI 0.36 to 1.44), or escalation of therapy (RR 0.36, 95% CI 0.09 to 1.39) and did not improve New York Heart Association functional class (RR 1.32, 95% CI 0.38 to 4.5) compared to MT. Incidence of study-drug discontinuation was similar between groups (RR 0.89, 95% CI 0.53 to 1.48). CT did not decrease the combined end point of mortality, admission for worsening PAH, lung transplantation, or escalation of PAH therapy (RR 0.42, 95% CI 0.17 to 1.04). In conclusion, this meta-analysis suggests that in PAH CT does not offer an advantage over MT apart from modestly increasing exercise capacity. However, given the paucity of good-quality data, more studies are required to define the efficacy of CT in this population before establishing final guidelines.

The occurrence and impact of coronary artery disease (CAD) among patients with pulmonary arterial hypertension (PAH) are unknown. We aimed to determine the prevalence, clinical correlates, and effect of CAD in patients with PAH. We reviewed the medical records of consecutive patients diagnosed with PAH at a university-based referral center for pulmonary vascular disease from January 1990 to May 2010. The patients systematically underwent right heart catheterization and coronary angiography as a part of their evaluation. The patients with PAH with CAD (defined as ≥50% stenosis in ≥1 major epicardial coronary artery) were compared to patients without CAD. Among the 162 patients with PAH, the prevalence of CAD was 28.4%. The presence of CAD was associated with older age (66.6 ± 11.5 vs 49.2 ± 14.0 years, p0.001), systemic hypertension, and dyslipidemia. The patients with PAH and CAD had a lower mean pulmonary arterial pressure (44.6 ± 11.1 vs 49.2 ± 14.0 mm Hg; p = 0.02) than patients without CAD. During a median follow-up of 36 months, 73 patients died. The presence of CAD was a predictor of all-cause mortality on univariate analysis (hazard ratio 1.97, 95% confidence interval 1.21 to 3.20) but not on multivariate analysis, which identified older age (hazard ratio 1.03, 95% confidence interval 1.01 to 1.05) and right atrial pressure (hazard ratio 1.08, 95% confidence interval 1.03 to 1.14) as the only independent predictors. In conclusion, our study has demonstrated that CAD is common among patients with PAH. CAD prevalence increases with age, dyslipidemia, and hypertension, but we did not detect an independent prognostic effect of CAD on mortality.

Numerous studies have examined whether plasma D-dimer (DD) can be used to identify patients with acute aortic dissection (AAD). These studies have been inconclusive because of their limited sample sizes and the different cut-off values employed. We aimed to conduct a systematic review and meta-analysis to examine the utility of plasma DD as a screening tool for AAD. We systematically searched EMBASE and MEDLINE and hand-searched relevant articles to identify studies investigating plasma DD as a screening tool for AAD. A value of 500 ng/ml was defined as the threshold for a positive plasma DD finding because it is widely used for ruling out pulmonary emboli. Using DerSimonian-Laird random-effects models we pooled data across studies to estimate sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (LRs). We identified 7 studies involving 298 subjects with AAD and 436 without. When data were pooled across studies, sensitivity (0.97, 95% confidence interval [CI] 0.94 to 0.99) and negative predictive value (0.96, 95% CI 0.93 to 0.98) were high. Specificity (0.56, 95% CI 0.51 to 0.60) and positive predictive value (0.60, 95% CI 0.55 to 0.66) were low. Negative LR showed an excellent discriminative ability (0.06, 95% CI 0.03 to 0.12), whereas positive LR did not (2.43, 95% CI 1.89 to 3.12). In conclusion, our meta-analysis suggests that plasma DD

Individual socioeconomic factors have been associated with adverse cardiovascular outcomes. It is however unclear how the socioeconomic status of a community influences the characteristics and outcome of patients treated with percutaneous coronary intervention (PCI).The Israel Central Bureau of Statistics assigns a socioeconomic index (SI) to communities based on demographic, economic and educational parameters. We determined the SI for 1397 consecutive patients who underwent PCI between 4/2004 and 10/2006; patients were divided into low, intermediate or high SI. Baseline and procedural characteristics, adherence to guidelines - recommended medications and major adverse cardiac events (MACE) were compared between groups. Multivariate analysis was used to adjust for baseline and procedural variables.Patients from low SI communities were younger (59±11, 64±12, 65±11 years for low, middle and high SI groups respectively, P0.01) and had higher rates of diabetes (P0.04) and of smoking (P0.01). A low SI was associated with a lower rate of drug eluting stent implantation (P0.01), lower adherence to aspirin and clopidogrel therapy, a higher rate of repeat revascularization (P=0.04) and a higher rate of recurrent myocardial infarction. A lower SI was an independent predictor of MACE (H.R 1.52 - 95% CI 1.03-2.25).Among patients undergoing PCI, a low community socioeconomic level is associated with a higher prevalence of cardiovascular risk factors, lower adherence to guidelines recommended therapy and is an independent predictor of MACE during follow up.

Coronary artery perforation (CP) is a rare, sometimes lethal complication of percutaneous coronary intervention. There are limited controlled contemporary data regarding its predictors, incidence, and outcomes. The aim of this study was to define the incidence, associated factors, and outcomes of CP in the current era of coronary intervention. All patients who had CP during percutaneous coronary intervention at a large tertiary center from January 2001 to December 2008 were identified. Demographic, clinical, and procedural data and outcome variables were obtained. Patients with CP were compared with a randomly assigned control group. Fifty-seven patients with CP were identified among 9,568 interventions performed during the study period (0.59%); these patients were compared with 171 who underwent percutaneous coronary intervention without CP. Vessels were perforated by wires (52.6%), balloons (26.3%), and stents (21.1%). Perforations were classified using the Ellis classification. CP was associated with mortality and tamponade rates of 7% and 16%, respectively, but all these serious complications occurred with grade III perforations. Most grade I and II perforations were managed conservatively. Multivariate analysis identified the treatment of chronic total occlusion as the strongest independent predictor of CP; other independent variables included calcium in the coronary artery that was the site of intervention and non-ST elevation myocardial infarction.

Keyword: Coronary angiography, Invasive Computerized tomography including demographic, clinical, and angiographic data. All invasive angiograms in which isolated LM disease was questioned, were reviewed by an experienced operator, in particular looking for the presence of calcification and whether the lesion was ostial or not. Of 10,742 patients undergoing ICA during the study period, thirtysix (0.3%) also underwent CCTA shortly after ICA. Of this group, the indications for CCTA were: twenty-five (69%) for questionable LM spasm or disease, 3 (8%) for defining anomalous RCA origin, 2 (6%) for defining bypass grafts not demonstrated by ICA, 2 (6%) for questionable

Chronic lymphedema occurs frequently in breast cancer patients and is associated with significant morbidity and reduced quality-of-life. In this pilot study, the authors (1) addressed whether conducting a larger randomized controlled trial of aqua lymphatic therapy (ALT) would be feasible and (2) estimated the extent to which ALT combined with home-based exercise compared with home-based exercise alone would reduce arm disability in patients with breast cancer-related lymphedema.Twenty-five women with breast cancer-related lymphedema were randomized to either ALT in addition to a home land-based exercise program (ALT group; n = 13) or to a home land-based exercise program alone (control group; n = 12). The participants were evaluated before and after a 12-wk intervention period composed of weekly pool exercise sessions. Main outcome measures were arm volume, arm disability, pain, and quality-of-life.At follow-up, there was no statistical difference between the control and ALT groups in any of the outcomes, except for present pain intensity. At the end of the study period, there was no change in the lymphedematous limb volume in either group. Grip strength was improved in both groups. Only the ALT group showed a statistically significant difference with a reduction in pain intensity score and arm disability. Furthermore, quality-of-life significantly improved only in the ALT group.Conducting a larger randomized controlled trial would be feasible. In comparison with the beginning of the intervention, the participants in the ALT group showed significant beneficial changes after 12 wks of treatment, whereas the control group did not improve. ALT did not make the lymphedema volume worse and therefore may serve as a safe alternative to land-based treatments of breast cancer-related lymphedema.

Limited data is available regarding angiographic findings of young women presenting with acute coronary syndrome (ACS). Spontaneous coronary artery dissection (SCAD) may be a major cause of ACS in this population. Coronary angiograms of 366 women (age ≤ 55 years) enrolled in the GENESIS PRAXY

Morbidity from pulmonary arterial hypertension (PAH) ensues when the pulmonary pressure reaches suprasystemic levels. A transcatheter alternative to the Potts shunt would allow decompression of the right heart without the surgical risks. To aid development of a transcatheter aortopulmonary shunt (TAPS) device, we described the anatomic relationship between the left pulmonary artery (LPA) and the descending aorta (dAO) in adults with severe pulmonary hypertension. Adults with severe PAH (peak systolic pulmonary arterial pressure [PASP] ≥80 mmHg) who had computed tomography of the chest were enrolled. Measurements were taken on the axial plane at the level of the pulmonary artery bifurcation. Forty patients (male sex, 9 patients; median age ± standard deviation [SD], [Formula: see text] years; median PASP ± SD, [Formula: see text] mmHg) were identified. The mean distance (±SD) between the LPA and dAO was [Formula: see text] mm. The mean luminal dAO and LPA diameters (±SD) were [Formula: see text] mm and [Formula: see text] mm, respectively. The LPA and dAO approximated in 93% of patients, with 38% having aortic calcification at the contact site. The mean "landing zone" width and height (defining an area with distance4 mm between the outer borders) of the two arteries were [Formula: see text] mm and [Formula: see text] mm, respectively, at a mean distance of [Formula: see text] mm from the main pulmonary artery bifurcation. This study shows that the landing zone is able to accommodate a TAPS device of up to 15 mm in diameter in the majority of patients with severe PAH.

High levels of circulating cell free DNA (CFD) have been associated with poor prognosis in various diseases. Data pertaining to CFD in acute myocardial infarction (MI) are scarce. The available data have been obtained by either electrophoresis or polymerase chain reaction. We evaluated a novel method for the detection of CFD in patients with ST elevation myocardial infarction (STEMI) and examined its correlation with established markers of necrosis and ventricular function.Serum concentrations of CFD, troponin-T and creatine kinase (CK) were measured simultaneously in 16 randomly selected acute STEMI patients upon admission and at three more time points. 47 healthy subjects served as a control group. CFD was quantified by a novel rapid fluorometric assay. Ejection fraction (EF) was assessed by echocardiography.Peak CFD levels were significantly higher in patients compared with controls (P = 0.001) and correlated with peak levels of CK and troponin-T (R = 0.79, P0.001); R = 0.65, P = 0.006, respectively). Peak CFD levels tended to be associated with lower EF (P = 0.075).With this method, CFD levels correlated with the levels of established markers of myocardial necrosis but not with EF. The kinetic pattern of CFD release after STEMI and its prognostic value require further investigation.

Postoperative atrial fibrillation (AF) is a serious yet common complication after coronary artery bypass grafting (CABG) surgery. Risk factors for postoperative AF have been identified, including echocardiographic parameters, and these are relied on to implement preventative strategies that reduce the incidence of AF. There has yet to be a study examining the impact of echocardiographic right-sided cardiac parameters on the prediction of postoperative AF. Thus, a panel of right-sided cardiac parameters was measured in a cohort of patients undergoing isolated CABG surgery, excluding those who did not have echocardiographic assessment within 30 days before surgery and those with any history of AF. The primary outcome was postoperative AF defined as any episode of AF requiring treatment during the index hospitalization. Postoperative AF occurred in 197 of 768 patients (25.6%); these were older and more likely to have hypertension and chronic kidney disease. After adjustment for clinical and echocardiographic variables, left atrial volume index ≥34 ml/m 2 (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.36 to 2.87), abnormal right ventricular myocardial performance index (OR 1.50, 95% CI 1.01 to 2.24), and advancing age (OR 1.05, 95% CI 1.03 to 1.07) were found to be independent predictors of postoperative AF. In conclusion, right ventricular myocardial performance index is a novel predictor of postoperative AF in patients undergoing isolated CABG surgery and appears to be additive to established risk factors such as age and left atrial volume.

Limited data exist regarding the management of patients with acute coronary syndrome (ACS) in high-income countries compared with low/middle-income countries. We aimed to compare in-hospital trends of revascularization and prescription of medications at discharge in patients with ACS from high-income (Canada and United States) and low/middle-income (India, Iran, Pakistan, and Tunisia) countries. Data from a double-blind, placebo-controlled, randomized trial investigating the effect of bupropion on smoking cessation in patients after an enzyme-positive ACS was used for our study. A total of 392 patients, 265 and 127 from high-income and from low/middle-income countries, respectively, were enrolled. Patients from high-income countries were older, and were more likely to have diagnosed hypertension and dyslipidemia. During the index hospitalization, patients from high-income countries were more likely to be treated by percutaneous coronary intervention (odds ratio [OR] 19.7, 95% confidence interval [CI] 10.5 to 37.0). Patients with ST elevation myocardial infarction from high-income countries were more often treated by primary percutaneous coronary intervention (OR 16.3, 95% CI 6.3 to 42.3) in contrast with thrombolytic therapy (OR 0.24, 95% CI 0.14 to 0.41). Patients from high-income countries were also more likely to receive evidence-based medications at discharge (OR 2.32, 95% CI 1.19 to 4.52, a composite of aspirin, clopidogrel, and statin). In conclusion, patients with ACS in low/middle-income countries were less likely to be revascularized and to receive evidence-based medications at discharge. Further studies are needed to understand the underutilization of procedures and evidence-based medications in low/middle-income countries.

Obesity is the new epidemic and is associated with an increased risk of diastolic and systolic heart failure. Effective treatment options with drastic results such as bariatric surgery have raised interest in the possible reversal of some of the cardiovascular sequelae. Many studies have assessed individually the effect of weight loss on specific echocardiographic indices, mostly employing nonhomogeneous groups. The purpose of this narrative review is to summarise the effect of bariatric surgery on echocardiographic indices of biventricular function and to help in the understanding of the expected echocardiographic changes in bariatric patients after weight-loss surgery.

Background Smoking remains the most important modifiable risk factor for secondary prevention of cardiovascular events. We therefore performed a meta-analysis to determine the efficacy and safety of bupropion therapy started in-hospital for smoking cessation in patients with cardiovascular disease (CVD). Methods We systematically searched the medical literature to identify randomized controlled trials (RCTs) of in-hospital initiation of bupropion therapy for smoking cessation in patients with CVD. RCTs reporting smoking abstinence at 6 or 12 months were included. Results Three RCTs, including 773 patients, were included in our analyses. Participants were predominantly men (range of means, 69.0%-83.8%), and the majority were hospitalized with acute coronary syndrome (ACS) (range of means, 66%-100%). Treatment duration ranged from 8-12 weeks. At the end of treatment, bupropion was associated with a significant increase in point prevalence abstinence (relative risk [RR], 1.21; 95% confidence interval [CI], 1.02-1.45) but not continuous abstinence (RR, 1.19; 95% CI, 0.97-1.45). However, bupropion was not associated with a significant increase in point prevalence abstinence (RR, 1.17; 95% CI, 0.92-1.48) or continuous abstinence (RR, 1.16; 95% CI, 0.90-1.50) at 12 months. The results of the pooled analysis for major adverse cardiac and cerebrovascular events were inconclusive (RR, 1.28; 95% CI, 0.93-1.78). Conclusions We found that bupropion improved abstinence over placebo at the end of treatment but that this effect did not persist at 12 months. Because of inconsistent reporting of safety data, the safety profile of bupropion therapy in this patient population remains unclear.

Objective To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism. Design Systematic review and random effects meta-analysis. Data were extracted independently by two investigators. An adjusted indirect comparison was performed to compare between novel oral anticoagulants. Data sources Medline, Embase, and Cochrane Library (from inception to April 2012). Hand searching of relevant scientific works and contact with experts. Study selection Randomised controlled trials of novel oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism. Selected outcomes were recurrent events, major bleeding, and all cause mortality. Results Nine studies met our inclusion criteria, involving 16 701 patients evaluated for efficacy and 16 611 for safety. Data were stratified according to different novel oral anticoagulants. For recurrent acute venous thromboembolism, there were no significant differences in events rates between any of the anticoagulants and conventional treatment (rivaroxaban (four studies): relative risk 0.85, 95% confidence interval 0.55 to 1.31; dabigatran (two studies): 1.09, 0.76 to 1.57; ximelagatran (two studies): 1.06, 0.62 to 1.80; and apixaban (one study): 0.98, 0.20 to 4.79). Rivaroxaban reduced the risk of major bleeding compared with conventional treatment (0.57, 0.39 to 0.84), whereas other novel oral anticoagulants did not (0.76 (0.49 to 1.18) for dabigatran; 0.54 (0.28 to 1.03) for ximelagatran; 2.95 (0.12 to 71.82) for apixaban). For all cause mortality there were no significant differences between the novel oral anticoagulants and conventional treatment (0.96 (0.72 to 1.27) for rivaroxaban; 1.00 (0.67 to 1.50) for dabigatran; 0.67 (0.42 to 1.08) for ximelagatran; 6.89 (0.36 to 132.06) for apixaban). The adjusted indirect comparison between rivaroxaban and dabigatran did not show superiority of either drug over the others for major bleeding (0.75, 0.41 to 1.34) or the other endpoints. Conclusions Compared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding.

New oral anticoagulants have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). We performed a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of new oral anticoagulants to that of

Patients with pulmonary hypertension (PH) typically have exercise intolerance and limitation in climbing steps. To explore the exercise physiology of step climbing in PH patients, on a laboratory-based step test. We built a step oximetry system from an ‘aerobics’ step equipped with pressure sensors and pulse oximeter linked to a computer. Subjects mounted and dismounted from the step until their maximal exercise capacity or 200 steps was achieved. Step-count, SpO2 and heart rate were monitored throughout exercise and recovery. We derived indices of exercise performance, desaturation and heart rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level were measured. Lung function tests and hemodynamic parameters were extracted from the medical record. Eighty-six subjects [52 pulmonary arterial hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were recruited. Exercise performance (climbing time, height gained, velocity, energy expenditure, work-rate and climbing index) on the step test was significantly worse with PH and/or worsening WHO functional class (ANOVA, p

Background: Most pulmonary embolism (PE) research has focused on acute and short-term outcomes such as mortality and PE recurrence. Whether long-term morbidity such as exercise limitation, impaired quality of life (QOL) and persistent dyspnea occurs after PE is largely unstudied. To address this knowledge gap, we performed the ELOPE study, a prospective, observational, multicenter cohort study of long-term outcomes after acute PE (www.clinicaltrials.gov NCT01174628). Objectives: The objectives of the ELOPE (Evaluation of Long-term Outcomes after PE) Study were: (1) to describe and quantify degree of exercise limitation, QOL impairment and persistent dyspnea at 1 year after PE; and (2) to identify predictors of poor functional status at 1 year. Methods: Patients ≥18 years old with a 1st episode of acute PE diagnosed within the previous 10 days screened at 5 Canadian recruiting centers were potentially eligible to participate. Exclusion criteria were subsegmental-only PE, preexisting severe cardiopulmonary comorbidity, previous proximal DVT, contraindication to CT pulmonary angiography (CTPA), life expectancy After the Baseline (B) visit, patients attended follow-up (FU) visits at 1, 3, 6 and 12 months to measure QOL (SF-36, PEmbQoL), dyspnea (UCSD SOBQ), and 6-minute walk test (6MWT) [all FU visits]; undergo CTPA [B, 12], echocardiogram [B, 12], Q scan [6, 12], cardiopulmonary exercise testing (CPET) [1, 12] and pulmonary function tests [1, 12]; and measure biomarkers (BNP, ddimer, troponin) [B, 6]. The primary study outcome was maximal aerobic capacity defined by peak oxygen uptake (VO2) as a percent of predicted maximal VO2 (VO2max) on 1-year CPET, with For the present analysis, we summarized demographic and clinical characteristics of study subjects, the proportion of patients with VO2max Results: 984 patients were screened for participation; of these, 150 were eligible and 100 (67%) consented to participate. Mean (SD) age was 50 (15) years, 57% were male, 80% were outpatients and 33% had concomitant DVT. PE was provoked in 21% and unprovoked in 79%; none were cancer-related. At 1 year, 40/86 (46.5%) of patients had 80% predicted VO2max at 1 year. Independent baseline predictors of abnormal VO2max at 1 year included: male sex (relative risk (RR)= 3.2 [95% CI 1.3-8.1]; p=0.015), age (RR 0.98 [95% CI 0.96-0.99] per 1 year age increase; p=0.002), BMI (RR 1.1 [95% CI 1.01-1.2] per 1 kg/m2 BMI increase; p=0.023), and smoker (RR 1.8 [95% CI 1.1-2.9]; p=0.023). In addition, VO2max Conclusions: PE is a common and serious cardiovascular illness, yet clinically relevant information on characteristics and determinants of long-term outcome after PE have been lacking. Results of the ELOPE Study indicate that almost half of PE patients can be considered to have a "post-PE syndrome" characterized by exercise limitation at 1 year, which influences their QOL and degree of dyspnea. Predictors of this post-PE syndrome include male sex, younger age, higher BMI and smoking. CPET testing or 6MWT testing at 1 month may help to identify patients with a higher risk of post-PE syndrome at 1 year. Funding: Canadian Institutes of Health Research (MOP-93627) Disclosures Wells: Bayer: Honoraria; BMS/Pfizer: Research Funding.

Background: Biomarkers such as brain natriuretic peptide (BNP), high-sensitivity cardiac troponin (hsTnT) and d-dimer (DD) are useful for acute or short-term risk stratification after pulmonary embolism (PE) to predict right ventricular dysfunction, recurrent PE or death. However, whether acute or convalescent levels of these biomarkers predict longterm functional limitation after PE has not been evaluated. To address this knowledge gap, we performed the ELOPE (Evaluation of Longterm Outcomes after PE) Study, a prospective, observational, multicenter cohort study of long-term outcomes after acute PE (www.clinicaltrials.gov NCT01174628). Objectives: To describe levels of NT-proBNP, hsTnT and d-dimer at baseline and 6 months in patients with acute PE, and to assess the relationship between biomarker levels and functional status at 1 year. Methods: Patients ³ 18 years old with a 1st episode of acute PE diagnosed within the previous 10 days screened at 5 Canadian recruiting centers were potentially eligible to participate. Exclusion criteria were subsegmental-only PE, preexisting severe cardiopulmonary comorbidity, previous proximal DVT, contraindication to CT pulmonary angiography (CTPA), life expectancy Patients attended study visits at baseline, 1, 3, 6 and 12 months. Blood samples to assay NT-proBNP (serum), hsTnT (serum) and DD (plasma) were obtained at baseline and 6 months. NT-proBNP and hsTnT were measured using the cobas® 8000 modular analyzer (Roche Diagnostics, Laval, Quebec); cut-off for normal is The primary outcome for the ELOPE Study was maximal aerobic capacity as defined by peak oxygen uptake (VO2) as a percent of predicted maximal VO2 (VO2max) on a cardiopulmonary exercise test (CPET) performed at the 1-year visit, with For each biomarker at baseline and 6 months, we calculated median (IQR) values, % of values above the cutoff, and univariate relative risk (RR) for VO2max Results: 984 patients were screened for participation; of these, 150 were eligible and 100 (67%) consented to participate. Mean (SD) age was 50 (15) years, 57% were male, 80% were outpatients, and 33% had concomitant DVT. PE was provoked in 21% and unprovoked in 79%; none were cancer-related. Table. Median biomarker values, % of values above cutoff, and univariate RR for VO2max cut-off* 8 (10.1%) 4 (5.8%) 8 (10.1%) 5 (7.2%) 62 (78.5%) 8 (11.6%) Univariate RR for VO2 max In a multiple model adjusted for age and sex, baseline NT-proBNP >300 pg/mL was associated with a relative risk (RR) of 2.31 (95% CI 1.10, 4.86; p=0.027) for VO2max Conclusion: In a prospective cohort of patients with a first episode of PE without preexisting severe cardiopulmonary comorbidity, baseline NT-proBNP >300 pg/mL predicted a greater than 2-fold increased risk of abnormal CPET at 1 year after PE. This finding may allow early identification of PE patients at increased risk of poor longterm outcome after PE. Further analyses are in progress to assess the relationship between changes in biomarker levels from baseline to 6 months and 1-year CPET result. Funding: Canadian Institutes of Health Research (MOP-93627) Disclosures Wells: BMS/Pfizer: Research Funding; Bayer: Honoraria.

Cilostazol is a generic drug with antiplatelet and antiproliferative effects. It is unclear whether adding cilostazol to standard dual antiplatelet therapy (aspirin and clopidogrel) after percutaneous coronary intervention reduces restenosis and improves the outcomes. We, therefore, conducted a systematic review and meta-analysis. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials comparing dual antiplatelet therapy with and without cilostazol after percutaneous coronary intervention. The data were pooled using random-effects models and stratified into short-term (1-month), midterm (1- to 12-month), and long-term (≥12-month) follow-up durations. Twelve randomized controlled trials involving 5,655 patients met our inclusion criteria. The addition of cilostazol to dual antiplatelet therapy was not associated with a significant change in target lesion revascularization (TLR) and target vessel revascularization (TVR) at short-term follow-up. However, TLR and TVR were significantly reduced at midterm follow-up (relative risk 0.57, 95% confidence interval 0.39 to 0.84, and relative risk 0.62, 95% confidence interval 0.47 to 0.83, respectively). Data regarding TLR and TVR at long-term follow-up were limited and inconclusive. We did not find a difference in myocardial infarction, mortality, or major bleeding at any follow-up duration. In conclusion, the addition of cilostazol to dual antiplatelet therapy after percutaneous coronary intervention has favorable effects on TLR and TVR at 1 to 12 months, with no differences in adverse outcomes at any follow-up duration.