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Percutaneous coronary interventions (PCIs) are central to the treatment of coronary artery disease, but their invasive nature in conjunction with the use of anticoagulants makes bleeding complications an important peri-procedural risk. Any amount of bleeding, including minor bleeding, that results from PCI is associated with worse ischemic outcomes such as myocardial infarction, stent thrombosis and death. Establishing the incidence of bleeding associated with PCI is challenging owing to the lack of consistency in definitions used to define bleeding events and differences between clinical trial and registry data. The factors that translate bleeding events into worse clinical outcomes are not fully understood, but likely involve hypotension, tachycardia, reduced oxygen-carrying capacity and systemic inflammation. The use of blood transfusions does not appear to mitigate this risk, but actually appears to be independently associated with increased morbidity and mortality. A number of studies have demonstrat...

Enhanced recovery after surgery (ERAS) protocols have proven effective in a variety of surgical specialties. Published reports on these pathways within cardiac surgery and interventional cardiology are limited. Invasive aortic valve replacement procedures are increasingly being performed by hybrid groups of interventional cardiologists and surgeons through transcatheter aortic valve implantation (TAVI). The TAVI patient population is at a higher surgical risk compared with those undergoing surgical aortic valve replacement since they are older, frailer, and have significant co-morbidities which result in an increased risk of perioperative complications. ERAS protocols have the potential to help these patients undergoing TAVI procedures. In conclusion, we propose a TAVI ERAS protocol with a call-to-action for other centers to implement an ERAS protocol to improve hospital and cardiac outcomes.

Aims We aimed to determine the frequency of aortic valve surgery (AVR) with or without coronary artery bypass grafting (CABG), among patients with moderate/severe aortic stenosis (AS) and left ventricular systolic dysfunction (LVSD), and its relationship with survival. Methods and results The Duke Echocardiographic Database ( N = 132 804) was queried for patients with mean gradient ≥25 mmHg and/or peak velocity ≥3 m/s and LVSD (left ventricular ejection fraction ≤50%) from 1 January 1995–28 February 2014. For analyses purposes, AS was defined both by mean gradient and calculated aortic valve area (AVA) criteria. Time-dependent indicators of AVR in multivariable Cox models were used to assess the relationship of AVR and all-cause mortality. A total of 1634 patients had moderate ( N = 1090, 67%) or severe ( N = 544, 33%) AS by mean gradient criteria. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. There were 863 (53%) deaths observed up to 5 years following index echo. After multivariable adjustment in an inverse probability weighted regression model, AVR was associated with higher 5-year survival amongst patients with moderate AS and severe AS whether classified by AVA or mean gradient criteria. Over all, AVR ± CABG compared with medical therapy was associated with significantly lower mortality [hazard ratio, HR = 0.49 (0.38, 0.62), P < 0.0001]. Compared with CABG alone, CABG + AVR was associated with better survival [HR = 0.18 (0.12, 0.27), P < 0.0001]. Conclusions In patients with moderate/severe AS and LVSD, mortality is substantial and amongst those selected for surgery, AVR with or without CABG is associated with higher survival. Research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.

Background: In the current era of surgical and transcatheter aortic valve replacement (AVR), patients with severe symptomatic aortic stenosis (AS) receiving medical management after referral to a valve treatment center have not been well-described. Methods: The ACC Championing Care for the Patient with AS initiative involved 454 patients referred for assessment of AS treatment options to 9 US valve treatment centers from 11/2012 to 6/2014. We compared clinical characteristics of patients with severe symptomatic AS receiving medical management versus AVR using chi-square, Fisher’s exact, and t-tests. We identified reasons for medical management using summary statistics. Results: Among 454 patients referred to a valve center, 42 (9%) received medical management for insufficient AS severity, 76 (17%) received medical management despite having severe symptomatic AS, and 336 (74%) underwent AVR. Patients receiving medical management despite severe symptomatic AS were older with higher STS predicted mortality than patients treated with AVR (Table). Common reasons for medical management were patient preference (43%, including waiting for commercial TAVR), medical futility (17%), inoperability (11%, including infeasible aortic annulus for TAVR), and temporary bridging with valvuloplasty (15%). Conclusions: In the current era of transcatheter and surgical AVR, medical management often occurs among patients with severe symptomatic AS referred for AVR. As medical futility, inoperability, and patient preferences commonly contribute to this decision, both valve treatment centers and referring physicians should be well versed in supportive care strategies to improve health outcomes in these patients.

A 76-year-old woman presented with progressive heart failure and transfusion-dependent hemolytic anemia due to severe paravalvular aortic regurgitation 4 years after bioprosthetic aortic valve replacement. She was deemed not to be a candidate for redo cardiac surgery due to a porcelain aorta and multiple comorbid medical conditions. We describe the role of pre-procedure contrast-enhanced, ECG-gated computed tomographic angiography to characterize the anatomy of the paravalvular leak connection for appropriate occluder device selection leading to successful percutaneous closure and resolution of the paravalvular regurgitation and hemolytic anemia.

A 60-year-old man with end-stage heart failure underwent orthotopic heart transplantation. Before transplantation, he had elevated pulmonary artery (PA) pressures (60/17 mm Hg, mean PA 35 mm Hg) and pulmonary vascular resistance (PVR) (6.6 Wood units). Following transplantation, he initially did

A 33-year-old woman was evaluated for palpitations and a continuous murmur. Echocardiography demonstrated a dilated vascular structure posterior to the aortic root. Coronary angiography revealed a coronary–cameral fistula originating from the left main coronary artery emptying into the right

Acute myocarditis often mimics acute myocardial infarction (MI) and can present a diagnostic dilemma. A 16-year-old healthy female presented with vomiting, malaise and bradycardia. Workup revealed inferolateral ST-elevation and troponin >200 ng/mL. She was transferred to pediatric intensive care

Medicare has proposed bundled payment for coronary artery bypass surgery (CABG) and acute myocardial infarction with or without percutaneous coronary intervention (AMI/PCI). The 90 day bundled payment window encompasses home health and rehabilitation, and may lead to financial challenges for health

PURPOSE This study aimed to assess vascular contrast opacification and homogeneity using single-bolus contrast administration with hybrid thoracic and abdominopelvic computed tomographic angiography in patients with severe aortic valve stenosis. MATERIALS AND METHODS Combination electrocardiogram-gated thoracic and dual-source, high-pitch abdominopelvic computed tomographic angiography examinations of 50 patients with severe aortic stenosis between December 2013 and March 2014 were reviewed. Contrast administration was individualized to patient-specific physiology. Image analysis of vascular opacification was obtained and interdependencies of vascular contrast and homogeneity of contrast distribution were assessed. RESULTS The mean volume of contrast administered was 106 ± 11.7 mL. Mean attenuation was 371 ± 90.7 Hounsfield units (HU) in the thoracic aorta and 388 ± 95.9 HU in the abdominal aorta. Homogeneous opacification was obtained throughout with coefficient of variation of 11%. CONCLUSIONS Procedural planning for transcatheter aortic valve replacement can be achieved using a single-injection bolus contrast protocol in combination with a 2-part multidetector computed tomographic image acquisition technique with optimal opacification of major arterial structures.

Over the last decade, there have been tremendous advances in our ability to treat valvular heart disease and anatomic cardiac defects utilizing catheter-based approaches. At the same time, the number of patients with acquired valvular heart disease or adult congenital heart disease who may benefit

This study sought to compare the accuracy of 2-dimensional transesophageal echocardiography (TEE) and computed tomography angiography (CTA) for noninvasive aortic annular sizing as required for transcatheter aortic valve implantation (TAVI). Direct intraoperative (OR) sizing is the gold standard for aortic annular measurement in surgical aortic valve replacement. Unlike surgical aortic valve replacement, TAVI requires noninvasive assessment of aortic annular dimensions for determining the size of prosthesis to be implanted and controversy exists regarding the best imaging technique for TAVI sizing. Preoperative CTA and OR TEE images of the aortic annulus in 227 patients who underwent proximal aortic surgery with OR annular sizing at the Duke University Medical Center were reviewed. Both imaging techniques were compared with direct OR measurements of aortic annulus diameter using metric sizers as the gold standard. CTA overestimated aortic annulus diameter in 72.2% of cases, with 46.3% >1 TAVI valve-size (>3 mm) overestimations, whereas TEE underestimated aortic annulus diameter in 51.1% of cases, with 16.7% >1 valve-size underestimations. Combining both techniques improved the estimation of aortic annular size. In conclusion, there are limitations to current imaging techniques for noninvasive determination of aortic annular dimensions compared with direct OR sizing. Undersizing by TEE and oversizing by CTA are common and may be related to differences in methods for sizing an elliptical structure. Combining measurements from both techniques would decrease the false exclusion rate for TAVI eligibility because of size mismatch.

Introduction: Aortic valve replacement (AVR) for aortic stenosis (AS) carries additional surgical risk in patients with left ventricular dysfunction (LVD) but has been associated with survival benefit. The current use of AVR and its relationship to mortality in patients with moderate or severe AS and LVD is ill defined. Hypothesis: We hypothesized that AVR was underutilized among patients with moderate/severe AS and LVD, and that it was associated with lower mortality. Methods: We queried the Duke Echocardiographic Database for patients with moderate (mean gradient >25 mmHg and/or peak velocity >3m/s) or severe AS (mean gradient >40 mmHg and or peak velocity >4m/s) and LVD (left ventricular ejection fraction [LVEF] Results: We identified a total of 1,634/132,804 patients with moderate (1,095, 67%) or severe (539, 33%) AS and LVD. Severe LVD (LVEF ≤35%) was present in 35% of the cohort. The median age of the cohort was 75 (IQR 67-83), and patients with moderate AS were more likely than those with severe AS to have a history of ischemic heart disease, diabetes, peripheral vascular disease, cerebrovascular disease, and renal disease (all p Median follow-up time was 1.2 years (IQR 0.2- 3.9). There were 863 deaths in the cohort. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. After multivariable adjustment, AVR with (n=270) or without CABG (n=280), compared to medical therapy was associated with lower mortality (HR=0.47 [0.38, 0.59], p Conclusions: Among patients with significant AS and LVD, AVR with or without CABG is associated with significant mortality benefit and may be underutilized in this population. Further research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.

Aims We sought to determine the feasibility of conducting percutaneous coronary intervention (PCI) in high-risk acute coronary syndrome (ACS) patients utilising the REG1 system consisting of pegnivacogin, an aptameric factor IXa inhibitor, and its controlling agent anivamersen. Methods and results In RADAR, ACS patients were randomised to pegnivacogin 1 mg/kg with 25%, 50%, 75%, or 100% anivamersen reversal or unfractionated heparin. Of the 640 patients randomised, 388 (61%) underwent PCI. Major modified ACUITY 30-day bleeding rates were 18% (25% reversal), 12% (50% reversal), 9% (75% reversal), and 7% (100% reversal), compared with 11% with heparin. The corresponding total bleeding rates were 68%, 39%, 35%, 34%, and 38% (heparin). Ischaemic events were less frequent in those receiving pegnivacogin versus heparin (4.4% vs. 7.3%, p=0.3). Thirty-day urgent TVR (1.1% vs. 0.9%, p=1.0), myocardial infarction (4.0% vs. 6.4%, p=0.3), and angiographic complication (11.2% and 10.8%, p=0.9) rates were similar with pegnivacogin and heparin. There were no incidences of clot formation on guidewires or catheters. Conclusions High-level factor IXa inhibition in ACS patients undergoing PCI, with at least 50% reversal, has a favourable bleeding profile and appears effective at suppressing ischaemic events and thrombotic complications. Larger phase trials in PCI are warranted. Clinical trials registration ClinicalTrials.gov NCT00932100.

The REG2 Anticoagulation System consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous active control agent, anivamersen. Its effect on thrombin generation is unknown. A prospectively designed thrombin generation study was conducted within the phase 1 ascending dose study of REG2 to assess the effect of REG2 on thrombin generation kinetics. A total of 32 healthy volunteers were recruited into four cohorts of ascending dose pegnivacogin for the phase 1 study. In this pre-specified substudy, blood samples were drawn in the presence or absence of corn trypsin inhibitor at specified times within each dosing cohort. Thrombin generation was initiated with tissue factor and thrombin generation kinetics were measured using the Calibrated Automated Thrombogram (CAT). REG2 attenuated thrombin generation in a dose-dependent manner. All parameters of the CAT assay, except for lag time, showed a dose and concentration-dependent response to pegnivacogin [time to peak thrombin generation (PTm), endogenous thrombin potential, peak thrombin generation, and velocity index (VIx)]. Reversal of the effect of pegnivacogin with anivamersen demonstrated restoration of thrombin generation without rebound effect. This first-in-human study of the effect of the REG2 Anticoagulation System on thrombin generation demonstrates concentration-dependent suppression of thrombin generation that is reversible without rebound effect, as measured by the CAT assay.

In this report, we describe a case of primary pericardial mesothelioma, which is an extremely rare tumor arising from mesothelial cells lining the pericardium and is associated with a dismal prognosis.

Background Up to one-third of patients diagnosed with left bundle branch block (LBBB) by conventional electrocardiographic (ECG) criteria are misdiagnosed. Strict LBBB shows decreased left ventricular pumping efficiency compared with nonstrict LBBB. However, no previous study has evaluated the frequency of strict LBBB after transcatheter aortic valve replacement (TAVR). The aim of this study was to determine the incidence of developing strict versus nonstrict LBBB after TAVR and test the hypothesis that preprocedure QRS duration does not predict strict LBBB but predicts development of nonstrict LBBB. Methods All patients receiving TAVR between 4/2011 and 2/2013 (n = 71) with no preexisting bundle branch block or permanent pacemaker were included. Twelve-lead ECGs were acquired preprocedure and both 1-day and 1-month postprocedure. All ECGs were classified as strict LBBB, nonstrict LBBB, or no LBBB. Results Sixty-eight patients had ECGs eligible for final analysis. On postprocedure day 1, 25 (37%) of 68 patients developed strict LBBB, and 2 patients (3%) developed nonstrict LBBB. At 1-month follow-up, the 2 patients diagnosed with nonstrict LBBB had resolved to normal, and 5 (20%) of 25 patients with strict LBBB had resolved to normal. Preprocedure QRS duration did not predict strict LBBB ( P = .51). Because of the low incidence of nonstrict LBBB, QRS duration as a predictor of nonstrict LBBB could not be tested. Conclusions Almost all patients who developed evidence of LBBB after TAVR met the new strict criteria, indicating probable procedural injury to the left bundle branch. Preprocedural QRS duration did not predict the development of strict LBBB.

The clinical significance of persistent patent foramen ovale (PFO) is not well defined. Empirically, PFO has been associated with many clinical conditions. In cryptogenic stroke, migraine, and orthodeoxia/platypnea, a plausible biologic mechanism exists to support PFO closure as a possible treatment. Although transcatheter closure of PFO has been available for over 2 decades, it has remained controversial due to a paucity of evidence to guide patient and device selection. Contemporary studies investigating PFO closure as treatment for patients with these conditions have been published recently and longitudinal data regarding the safety and efficacy of the devices is now available. In this review, we aim to describe the potential clinical significance of a patent foramen in the adult, appraise the newest additions to the body of evidence, and discuss the safety, benefit, patient selection, and future of transcatheter treatment of PFO.

RADAR compared REG1 (25%, 50%, 75%, 100% reversal) with unfractionated heparin (UFH) in 640 acute coronary syndrome (ACS) patients (479 REG1 patients, 161 UFH patients) undergoing an invasive management strategy. We sought to determine whether the REG1 anticoagulation system allows for safer early arterial sheath removal following cardiac catheterization.REG1 patients had arterial sheath removal immediately post catheterization. We measured arterial sheath management outcomes and vascular access complications in patients who had sheath removal without vascular closure device implantation; 461 patients were included (349 REG1 patients, 112 UFH patients).The median (25th, 75th) time from end of catheterization to arterial sheath removal was shorter in REG1 arms regardless of reversal strategy (26 minutes [18, 46]) compared with UFH (210 minutes [102, 342]). There was no increase in median time from sheath removal to hemostasis (10 minutes [10, 20] and 10 minutes [10, 20]; P=.60); vascular access-site bleeding complications were numerically fewer with REG1 than UFH (6% vs 11%; odds ratio [OR], 0.57; 95% CI, 0.27-1.18; P=.14). There were no differences in time to ambulation or hospital length of stay between the groups.REG1 allows for very early arterial sheath removal following cardiac catheterization without increasing the time to hemostasis or vascular access-site bleeding complications. Further studies are needed to determine whether anticoagulation with REG1 will translate into shorter hospital lengths of stay and reduced costs in ACS patients.

To assess whether systemic inflammatory response syndrome is associated with morbidity and mortality in ST-elevation myocardial infarction.Secondary analysis of multicenter randomized controlled trials.Complement and reduction of infarct size after angioplasty or lytics project patients (n=1,903) with ST-elevation myocardial infarction undergoing fibrinolysis or mechanical reperfusion.None.The prevalence of systemic inflammatory response syndrome was described in the 1,186 patients (64.4%) with data available for all systemic inflammatory response syndrome criteria. Using multiple imputations for the 1,843 patients (96.8%) with available endpoints, we compared the 90-day prevalence of death, shock, heart failure, or stroke between patients with and without systemic inflammatory response syndrome at presentation and at 24 hours post admission. Systemic inflammatory response syndrome was defined as ≥2 of 1) heart rate90 beats/min, 2) respiratory rate20 breaths/min, 3) body temperature38 or36°C, or 4) leukocyte count12 or4×10/L. At presentation, 25.0% of patients met systemic inflammatory response syndrome criteria; at 24 hours, 8.1% of patients met systemic inflammatory response syndrome criteria. The primary outcome was more frequent among patients with systemic inflammatory response syndrome at presentation (31.0% vs 16.7%; adjusted hazard ratio, 1.78 [95% CI, 1.35-2.34]; p0.001) and at 24 hours (36.7% vs 11.1%; adjusted hazard ratio, 2.84 [95% CI, 2.03-3.97]; p0.001). Mortality at 90 days was also higher among patients with systemic inflammatory response syndrome at either time point. Each additional systemic inflammatory response syndrome criterion was independently associated with 90-day outcomes at the time of presentation (adjusted hazard ratio, 1.41 per systemic inflammatory response syndrome criteria [95% CI, 1.24-1.61]; p0.001) and at 24 hours (adjusted hazard ratio, 1.72 per systemic inflammatory response syndrome criteria [95% CI, 1.47-2.01]; p0.001).The diagnosis of systemic inflammatory response syndrome and the cumulative number of systemic inflammatory response syndrome criteria were independently associated with 90-day clinical outcomes in a population of patients with ST-elevation myocardial infarction. The independent association of this simple composite measure of the inflammatory response with outcomes underscores the importance of the clinical inflammatory response in ST-elevation myocardial infarction.

High-risk percutaneous coronary interventions (PCI) are becoming more prevalent as the ability to perform complex coronary interventions continues to improve. Patients for whom high-risk interventions are considered generally have severe diffuse coronary artery disease, a single last patent conduit, or significant left main disease with large territories of myocardial ischemia. In addition, these patients also typically have reduced left ventricular function (ejection fraction

Antiplatelet therapy serves an important role in the management of acute coronary syndromes and in reducing the risk of thrombotic complications from atrial fibrillation. There has been rapid development of newer and more potent antiplatelet therapies over the last several years that have further reduced ischemic complications, but with a trade-off of increased bleeding risk. Bleeding complications associated with antiplatelet and anticoagulant therapies are associated with significantly increased risk of adverse outcomes, including death. Understanding the risk of bleeding associated with antiplatelet agents is critical to developing strategies to mitigate this risk.

Antithrombotic agents including anticoagulants and antiplatelets are the cornerstone of treatment of acute coronary syndromes. Currently available anticoagulants have several important limitations including unpredictable pharmacodynamics, immunogenicity, and difficulty in reversibility. A potent anticoagulant that has predictable efficacy, is easily reversible should the clinical need arise, and reduces ischemic events without an increase in bleeding risk would overcome many of the current limitations. Inhibition of factor IX in the coagulation cascade has shown promise as a target for development of a novel anticoagulant with a favorable bleeding risk. Aptamers are small oligonucleotides that can be developed to inhibit specific protein targets with high affinity and used as active drugs. Because aptamers are made of oligonucleotide sequences, they provide the code for their own complement (reversal agent) that can be developed and used to inhibit their function. The REG1 anticoagulation system is a novel, aptamer-based, factor IXa inhibitor that is being developed for use in patients undergoing percutaneous coronary intervention and the treatment of acute coronary syndrome.

Antiplatelet therapy serves an important role in the management of acute coronary syndromes and in reducing the risk of thrombotic complications from atrial fibrillation. There has been rapid development of newer and more potent antiplatelet therapies over the last several years that have further reduced ischemic complications, but with a trade-off of increased bleeding risk. Bleeding complications associated with antiplatelet and anticoagulant therapies are associated with significantly increased risk of adverse outcomes, including death. Understanding the risk of bleeding associated with antiplatelet agents is critical to developing strategies to mitigate this risk.

*Department of Medicine, University of North Carolina, Chapel Hill, NC; Division of Cardiology, University of North Carolina, Chapel Hill, NC;and Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC, USATo cite this article: Vavalle JP, Wu SS, Hughey R, Madamanchi NR, Stouffer GA. Plasma fibronectin levels and coronary artery disease. J ThrombHaemost 2007; 5: 864–6.

Synaptosome-associated protein of 25 kDa (SNAP-25) is a presynaptic membrane protein that has been clearly implicated in membrane fusion in both developing and mature neurons, although its mechanisms of action are unclear. We have now identified a novel SNAP-25-interacting protein named SNIP. SNIP is a hydrophilic, 145-kDa protein that comprises two predicted coiled-coil domains, two highly charged regions, and two proline-rich domains with multiple PPXY and PXXP motifs. SNIP is selectively expressed in brain where it co-distributes with SNAP-25 in most brain regions. Biochemical studies have revealed that SNIP is tightly associated with the brain cytoskeleton. Subcellular fractionation and immunofluorescence localization studies have demonstrated that SNIP co-localizes with SNAP-25 as well as the cortical actin cytoskeleton, suggesting that SNIP serves as a linker protein connecting SNAP-25 to the submembranous cytoskeleton. By using deletion analysis, we have mapped the binding domains of SNIP and SNAP-25, and we have demonstrated that the SNIP-SNAP-25 association is mediated via coiled-coil interactions. Moreover, we have shown that overexpression of SNIP or its SNAP-25-interacting domain inhibits Ca(2+)-dependent exocytosis from PC12 cells. These results indicate that SNIP is involved in regulation of neurosecretion, perhaps via its interaction with SNAP-25 and the cytoskeleton.

Bei einer Vielzahl von infektiosen, aber auch bei nicht infektiosen Erkrankungen wird das systemische inflammatorische Response-Syndrom (SIRS) beobachtet. Ein Autorenteam hat bei Patienten mit ST-Hebungsinfarkt aus 2 grosen Studien die Pravalenz und die prognostische Bedeutung dieses Syndroms untersucht.

Source Citation Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010;11:627-36. 2...

A 29-year-old female presented with intermittent nausea, vomiting, fevers, abdominal pain and fatigue. CT scans of the abdomen revealed inflammatory changes within the mesentery and small bowel. Histopathology of the mesentery and omentum showed chronic inflammation and fibrosis, supporting a diagnosis of sclerosing mesenteritis. Over the past 2 years, the patient suffered debilitating paroxysmal abdominal pain despite treatment with prednisone, azathioprine, sulfasalazine and narcotics. Additionally, she developed sacroiliitis diagnosed clinically and on radiographs. Intravenous infliximab (5 mg/kg intravenous) was initiated and continued every 6 weeks for 3 years. The patient has since had a dramatic improvement in her back and abdominal symptoms and has tapered off of prednisone, azathioprine and narcotics. Erythrocyte sedimentation rate, anaemia, leukocytosis and radiographic findings improved after initiation with infliximab. In conclusion, the authors report successfully treating sclerosing mesenteritis with sacroiliitis by the addition of infliximab. This may implicate a role for tumour necrosis factor α in disease pathogenesis.

Objectives This study sought to determine if there is an association between bleed location and clinical outcomes in acute coronary syndromes (ACS) patients. Background The prognostic significance of bleeding location among ACS patients undergoing cardiac catheterization is not well known. Methods We analyzed in-hospital bleeding events among 9,978 patients randomized in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) study. Bleeding events were categorized by location as access site, systemic, surgical, or superficial, and severity was graded using the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definition. We assessed the association of each bleeding location and severity with 6-month risk of death or myocardial infarction using a multicovariate-adjusted Cox proportional hazard model. Results A total of 4,900 bleeding events were identified among 3,694 ACS patients with in-hospital bleeding. Among 4,679 GUSTO mild/moderate bleeding events, only surgical and systemic bleeds were associated with an increased risk of 6-month death or myocardial infarction (adjusted hazard ratio [HR]: 2.52 [95% confidence interval (CI): 2.16 to 2.94, and 1.40 [95% CI: 1.16 to 1.69], respectively). Mild/moderate superficial and access-site bleeds were not associated with downstream risk (adjusted HR: 1.17 [95% CI: 0.97 to 1.40], and 0.96 [95% CI: 0.82 to 1.12], respectively). Among 221 GUSTO severe bleeds, surgical bleeds were associated with the highest risk (HR: 5.27 [95% CI: 3.80 to 7.29]), followed by systemic (HR: 4.48 [95% CI: 2.98 to 6.72]), and finally access-site bleeds (HR: 3.57 [95% CI: 2.35 to 5.40]). Conclusions Among ACS patients who develop in-hospital bleeding, systemic and surgical bleeding are associated with the highest risks of adverse outcomes regardless of bleeding severity. Although the most frequent among bleeds, GUSTO mild/moderate access-site bleeding is not associated with increased risk. These data underscore the importance of strategies to minimize overall bleeding risk beyond vascular access site management.