BACKGROUND:Coronary artery calcification is common among patients undergoing percutaneous coronary intervention (PCI), and severe coronary artery lesion calcification is associated with increased procedural complexity, stent under-expansion, and high rates of intraprocedural complications and out-of-hospital adverse events. Whether calcium ablation before stent implantation can mitigate these adverse events is not currently established. We aimed to prospectively compare orbital atherectomy with a balloon angioplasty-based strategy before stent implantation for the treatment of severely calcified coronary lesions. METHODS:In this multicentre, open-label, randomised controlled trial conducted at 104 medical centres in the USA, patients (aged ≥18 years) with severely calcified coronary lesions were randomly assigned (1:1) to orbital atherectomy or balloon angioplasty before PCI with drug-eluting stents using a web-based system (block sizes of four and six) and stratified by intended treatment of single versus multiple lesions and enrolling site. Randomly assigned lesions were deemed by operators to be eligible for both treatment strategies. Operators and patients were not masked to treatment. The two powered coprimary study endpoints were target vessel failure at 1 year (a composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target vessel revascularisation) and post-procedural minimal stent area at the site of maximal calcification, as assessed by intravascular optical coherence tomography in an imaging patient cohort. Primary analyses were by intention-to-treat. The trial is registered at ClinicalTrials.govNCT03108456, and 2-year follow-up is ongoing. FINDINGS:From March 27, 2017, to April 13, 2023, 2005 patients with 2492 lesions were randomly assigned to lesion preparation with orbital atherectomy (1008 patients with 1250 lesions) or balloon angioplasty (997 with 1242 lesions) before stent implantation. Median patient age was 70·0 years (IQR 64·0-76·0). 541 (27·0%) of 2005 patients were female and 1464 (73·0%) were male. Angiographically severe calcium was confirmed by the core laboratory in 1088 (97·1%) of 1120 lesions assigned to orbital atherectomy and 1068 (97·0%) of 1101 lesions assigned to balloon angioplasty. PCI was guided by intravascular imaging in 627 (62·2%) of 1008 patients in the orbital atherectomy group and 619 (62·1%) of 997 in the balloon angioplasty group. Target vessel failure events within 1 year occurred in 113 of 1008 patients in the orbital atherectomy group (1-year target vessel failure 11·5% [95% CI 9·7 to 13·7]) and in 97 of 997 patients in the balloon angioplasty group (10·0% [8·3 to 12·1]; absolute difference 1·5% [96% CI -1·4 to 4·4]; hazard ratio 1·16 [96% CI 0·87 to 1·54], p=0·28). Among those in the optical coherence tomography substudy cohort (276 patients with 286 lesions in the orbital atherectomy group and 279 patients with 292 lesions in the balloon angioplasty group), the mean minimal stent area at the site of maximal calcification was 7·67 mm2 (SD 2·27) in the orbital atherectomy group and 7·42 mm2 (2·54) in the balloon angioplasty group (mean difference 0·26 [99% CI -0·31 to 0·82]; p=0·078). Cardiac death events within 1 year occurred in 39 of 1008 patients in the orbital atherectomy group and in 26 of 997 in the balloon angioplasty group. INTERPRETATION:Routine treatment with orbital atherectomy before drug-eluting stent implantation did not increase minimal stent area or reduce the rate of target vessel failure at 1 year compared with a balloon angioplasty-based approach in severely calcified lesions deemed eligible for both treatment strategies. These data support a balloon-first approach for most calcified coronary artery lesions that can be crossed and dilated before stent implantation, guided by intravascular imaging. FUNDING:Abbott Vascular (Abbott).

Background Diastolic dysfunction is a predictor of poor outcomes in many cardiovascular conditions. At present, it is unclear whether diastolic dysfunction predicts adverse outcomes in patients with atypical aortic stenosis who undergo aortic valve replacement (AVR). Methods Five hundred and twenty-three patients who underwent transcatheter AVR (TAVR) ( n = 303) and surgical AVR (SAVR) ( n = 220) at a single institution were included in our analysis. Baseline left and right heart invasive hemodynamics were assessed. Baseline transthoracic echocardiograms were reviewed to determine aortic stenosis subtype and parameters of diastolic dysfunction. Aortic stenosis subtype was categorized as typical (normal flow, high-gradient) aortic stenosis, classical, low-flow, low-gradient (cLFLG) aortic stenosis, and paradoxical, low-flow, low-gradient (pLFLG) aortic stenosis. Cox proportional hazard models were utilized to examine the relation between invasive hemodynamic or echocardiographic variables of diastolic dysfunction, aortic stenosis subtype, and all-cause mortality. Propensity-score analysis was performed to study the relation between aortic stenosis subtype and the composite outcome [death/cerebrovascular accident (CVA)]. Results The median STS risk was 5.3 and 2.5% for TAVR and SAVR patients, respectively. Relative to patients with typical aortic stenosis, patients with atypical (cLFLG and pLFLG) aortic stenosis displayed a significantly higher prevalence of diastolic dysfunction (LVEDP ≥ 20mmHg, PCWP ≥ 20mmHg, echo grade II or III diastolic dysfunction, and echo-PCWP ≥ 20mmHg) and, independently of AVR treatment modality, had a significantly increased risk of death. In propensity-score analysis, patients with atypical aortic stenosis had higher rates of death/CVA than typical aortic stenosis patients, independently of diastolic dysfunction and AVR treatment modality. Conclusion We demonstrate the novel observation that compared with patients with typical aortic stenosis, patients with atypical aortic stenosis have a higher burden of diastolic dysfunction. We corroborate the worse outcomes previously reported in atypical versus typical aortic stenosis and demonstrate, for the first time, that this observation is independent of AVR treatment modality. Furthermore, the presence of diastolic dysfunction does not independently predict outcome in atypical aortic stenosis regardless of treatment type, suggesting that other factors are responsible for adverse clinical outcomes in this higher risk cohort.

INTRODUCTION:The available oral anti-Xa agents are routinely used for the management of thrombotic disorders. A molecularly modified recombinant coagulation FXa, also known as Andexanet Alfa (AA), that has been developed as an antidote to neutralize the bleeding effects of oral FXa inhibitors, such as Apixaban and Rivaroxaban.MATERIALS AND METHODS:This study utilized thromboelastography (TEG 5000 Hemostasis System), to investigate the neutralizing effects of AA at different concentrations of oral FXa inhibitors measuring such parameters as R-Time, K-Time, Angle, and Max Amplitude (MA). Apixaban, Betrixaban, Edoxaban, and Rivaroxaban were obtained commercially in powdered form. Each of these drugs was supplemented with freshly drawn whole citrated blood at a concentration of 1 μg/mL. And subsequently mixed with AA at 50 or 100 μg/mL.RESULTS:At a concentration of 1 μg/mL, all FXa inhibitors produced variable anticoagulant effects in the order of Edoxaban > Betrixaban > Rivaroxaban > Apixaban. AA at 100 μg/mL produced a complete neutralization of these inhibitors whereas at 50 μg/mL relatively weaker neutralization as measured by various parameters.CONCLUSION:These results suggest that regardless of the variable anticoagulant effects exhibited by the FXa Inhibitors, AA at FC = 100 μg/mL fully neutralized these agents as measured by the TEG parameters. AA was shown to be more effective in neutralizing Betrixaban and least effective in Apixaban. The neutralization of various FXa inhibitors was dose and donor-dependent warranting dosage adjustment for optimal outcomes.

BACKGROUND:Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is the most common cause of mortality following AMI, and treatment algorithms vary widely. We report the results of an analysis using time-sensitive, hemodynamic goals in the treatment of AMI-CS in a single center study. METHODS:Consecutive patients with AMI-CS from November 2016 through December 2021 were included in our retrospective analysis. Clinical characteristics and outcomes were analyzed using the electronic medical records. We identified 63 total patients who were admitted to our center with AMI-CS, and we excluded patients who did not have clear timing of AMI onset or CS onset. We evaluated the rate of survival to hospital discharge based on the quantity of certain time-sensitive hemodynamic goals were met. RESULTS:We identified 63 patients who met criteria for AMI-CS, 39 (62%) of whom survived to hospital discharge. Odds of survival were closely related to the achievement of four time-dependent goals: cardiac power output (CPO) >0.6 Watts (W), pulmonary artery pulsatility index (PAPi) >1, lactate <4 mmol/L, and <2 vasopressors required. Of the 63 total patients, 36 (57%) received intra-aortic balloon pump (IABP) and 18 (29%) received an Impella CP (Abiomed) as an initial mechanical circulatory support strategy. Six patients were escalated from IABP to Impella CP for additional hemodynamic support. Nine patients were treated with vasopressors/inotropes alone. Regarding the 39 patients who survived to hospital discharge, 75% of patients met 3 or 4 goals at 24 h, whereas only 16% of deceased patients met 3 or 4 goals at 24 h. Of the 24 patients who did not survive to hospital discharge, 18 (75%) met either 0-1 goal at 24 h. There was no effect of the initial treatment strategy on achieving 3-4 goals at 24 h. CONCLUSION:Our study evaluated the association of meeting 4 time-sensitive goals (CPO >0.6 W, PAPi >1, <2 vasopressors, and lactate <4 mmol/L) at 24 h after treatment for AMI-CS with in-hospital mortality. Our data show, in line with previous data, that the higher number of goals met at 24 h was associated with improved in-hospital mortality regardless of treatment strategy.

Elkaryoni, Ahmeda; Elgendy, Islam Y.b; Qarajeh, Raedc; Allen, Sorchaa; Abdelkarim, Islamc; Mallas, Waddahd; Leya, Ferdinand S.a; Lewis, Bruce E.a; Steen, Lowell H.a; Lopez, John J.a; Darki, Amira Author Information

Abstract Background Tricuspid regurgitation (TR) often occurs concomitantly with severe aortic stenosis. Post-operative worsening of tricuspid regurgitation has been observed after surgical and transcatheter aortic valve replacement (SAVR, TAVR) [1,2]. Purpose Pre-procedural severe tricuspid regurgitation has been shown to be a predictor of all-cause mortality in patients undergoing transcatheter aortic valve replacement (TAVR) [3,4]. However, little is known about the incidence of worsening tricuspid regurgitation after SAVR and TAVR and the impact on post-procedural outcomes. This study aims to evaluate, characterize and compare the incidence of worsening TR after TAVR and SAVR. Methods Retrospective single-center study of patients undergoing Transcatheter and Surgical Aortic Valve Replacement for severe aortic stenosis between 2014 and 2020. Incidence of tricuspid regurgitation was noted on echocardiogram at baseline and 1 year after TAVR or SAVR. This study enrolled 430 patients in the TAVR group and 237 patients in the SAVR group. The SAVR group only included patients who underwent isolated SAVR without any other valve intervention. Patients with severe TR at baseline were excluded from the study. Progression of TR severity was defined as deterioration by at least 1 grade of severity compared to baseline on echocardiography. Multivariable logistic regression analysis was performed to identify associations with worsening TR. Results Mean age of TAVR patients was higher than the SAVR patients (79±9 vs 68±12 years, p<0.0001). TAVR patients also had a significantly higher EuroSCORE than the SAVR patients (8.0±7 vs 3.5±4, p<0.0001). TAVR group was more likely to have atrial fibrillation than the SAVR group (34% vs 24%, p=0.006). Baseline right ventricular dysfunction and right ventricular enlargement were significantly higher in the TAVR group compared to the SAVR group [9% vs 4%, (p=0.009) and 10% vs 6%, (p=0.04), respectively]. Progression of TR severity occurred in 21.8% (94/430) of TAVR patients and 31.2% (74/237) of SAVR patients. Majority of these patients progressed from absent TR to mild TR [13.2% (57) in TAVR group vs 19.8% (47) in SAVR group (p=0.02)]. 6.3% (27) of patients in the TAVR group and 8.8% (21) of patients in the SAVR group had mild to moderate worsening of TR (p=0.22). 1.63% (7) in the TAVR group and 2.1% (5) in the SAVR group had progression from moderate to severe TR (p=0.65). On multivariable analysis, SAVR (Odds ratio, 2.46 [CI, 1.6–3.7]) and age (Odds ratio, 1.03 [CI, 1.03–1.05]) were associated with worsening TR severity. Conclusions In this retrospective observational study, SAVR and age were found to be associated with worsening tricuspid regurgitation. Majority of these patients progressed from absent TR to mild TR after SAVR. Further studies are necessary to determine long term outcomes of worsening tricuspid regurgitation after TAVR and SAVR. Funding Acknowledgement Type of funding sources: None.

Background Aortic pseudoaneurysm (AP) is a late complication of aortic repair that, without intervention, carries a high mortality rate. Surgical repair has significant in-hospital mortality and high health care costs. Endovascular stent grafting use is currently limited to branch-free aortic segments or the use of complex fenestrated devices. Our objective was to review the literature and share our institution’s experience with AP percutaneous closure by vascular plugs and occluder technology. Methods We retrospectively reviewed percutaneous AP closure cases published in the literature (2005-2016) and from our institution (2017-2019). The follow-up strategy in our institution group was up to the discretion of the performing physician. We measured the procedure’s safety, complications, and follow-up outcomes. Results We found 40 cases in the literature and 10 at our institution. The procedural success rate was 90% in the literature and 100% in our group. Our group’s average length of stay was 1.9 days with no observed major procedural complications. The literature’s follow-up was generally limited to the hospitalization period. Our patients had a median follow-up time of 12 months (range 3-47 months). Late follow-up of AP demonstrated that sac size remained stable or reduced in 6 patients, but a size increase was observed in 4 patients requiring surgical intervention. Death from nonprocedure-related complications occurred in 40% of our patients. The cost per procedure was hypothetically less than for performing open surgical repair. Conclusions Our experience shows a viable option for percutaneous AP repair, given its initial safety and cost-effectiveness. Our experience highlights the critical role of follow-up imaging in identifying AP expansion and the need for further intervention. The high nonaorta-related mortality seen in follow-up emphasizes the high-risk nature of the population due to comorbidities.

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.

Abstract Background Spontaneous coronary artery dissection (SCAD) is a common, non-atherosclerotic cause of myocardial infarction (MI). While conservative therapy is preferred in most cases, its role among those presenting as ST-elevation myocardial infarction (STEMI) remains undefined. Purpose We aimed to explore outcomes of SCAD causing STEMI, stratifying cases by involved coronary artery and revascularization status. Methods We used the Nationwide Readmission Database (2015–2018) to identify patients hospitalized with STEMI by using ICD-10-Clinical modification codes, and then stratified them into SCAD or no-SCAD groups. Each group was further subdivided by involved coronary artery (i.e., left main, left anterior descending, left circumflex, or right coronary artery), and if revascularization (i.e., percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)) was performed. We excluded patients >55 years old or with iatrogenic dissection. The age restriction allows us to compare a similarly aged group of patients. The primary outcome was in-hospital mortality. Cardiogenic shock, acute kidney injury, mechanical complications, length of stay, and 30-day readmission for all-cause, heart failure or MI were secondary outcomes. Results Of the 17,556 patients with STEMI identified, 338 (1.9%) had SCAD. Patients with SCAD were younger (median age (IQR) 46.0 (33–90) vs 49.0 (41–57); p<0.001) and more likely to be female (67% vs 21.6%, p<0.001). They were less likely to have PCI (55.3% vs. 80.7%; p<0.001), more likely to undergo CABG (4.7% vs 1.3%; p<0.001), with left main and left anterior descending coronary arteries more often affected (2.4% vs 1.1%, and 53.3% vs 48.6%; p for both =0.05, respectively). In-hospital mortality did not differ between groups (3.6% vs 3.3, p=0.81). Revascularization was associated with lower in-hospital mortality among no-SCAD patients (2.6% vs 7.0%, p<0.001), but not among SCAD patients (4.0% vs 3.1%, p=0.76) even when stratified by involved coronary artery. Revascularization among SCAD patients was associated with lower 30-day readmission rates for MI (0.0% vs 2.8%, p=0.05). SCAD patients were less likely to have acute kidney injury (6.5% vs 11.2%, p=0.01), but had a longer length of stay (median (IQR) 3.0 (1.0–6.0) vs 2.0 (1.0–4.0), p<0.001). Both groups had similar rates of cardiogenic shock (11.8% vs 10.6%, p=0.56), mechanical complications (0.6% vs 0.3%, p=0.22), and 30-day readmission rates for all-cause, and heart failure. Conclusion In-hospital mortality did not differ between patients with STEMI due to SCAD or no-SCAD. Although revascularization was not associated with lower in-hospital mortality among SCAD patients (regardless of involved coronary artery), their 30-day readmission rate for MI was lower suggesting further studies are warranted to explore patient subsets of SCAD that may benefit from revascularization. Funding Acknowledgement Type of funding sources: None.

Because timely primary percutaneous coronary intervention (PPCI) is the preferred therapy for ST-segment elevation myocardial infarction (STEMI), 1 Levine GN Bates ER Blankenship JC Bailey SR Bittl JA Cercek B Chambers CE Ellis SG Guyton RA Hollenberg SM Khot UN Lange RA Mauri L Mehran R Moussa ID Mukherjee D Ting HH O'Gara PT Kushner FG Ascheim DD Brindis RG Casey Jr, DE Chung MK de Lemos JA Diercks DB Fang JC Franklin BA Granger CB Krumholz HM Linderbaum JA Morrow DA Newby LK Ornato JP Ou N Radford MJ Tamis-Holland JE Tommaso CL Tracy CM Woo YJ Zhao DX 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction [published correction appears in J Am Coll Cardiol 2016;67:1506]. J Am Coll Cardiol. 2016; 67: 1235-1250 Crossref PubMed Scopus (523) Google Scholar there has been a substantial growth in the number of PPCI centers in the United States. 2 Langabeer JR Henry TD Kereiakes DJ Dellifraine J Emert J Wang Z Stuart L King R Segrest W Moyer P Jollis JG Growth in percutaneous coronary intervention capacity relative to population and disease prevalence. J Am Heart Assoc. 2013; 2e000370 Crossref PubMed Scopus (57) Google Scholar Oftentimes, there remains a need for interhospital STEMI transfers from noncapable percutaneous coronary intervention (PCI) centers to PPCI centers, and it is unclear if such an expansion has led to a change in the real-world practice landscape for STEMI transfers. 2 Langabeer JR Henry TD Kereiakes DJ Dellifraine J Emert J Wang Z Stuart L King R Segrest W Moyer P Jollis JG Growth in percutaneous coronary intervention capacity relative to population and disease prevalence. J Am Heart Assoc. 2013; 2e000370 Crossref PubMed Scopus (57) Google Scholar Thus, we aimed to explore trends and outcomes for STEMI transfers using the Nationwide Inpatient Sample (NIS) from 2008 to 2018.

Contemporary tools used to risk stratify patients with acute pulmonary embolism (PE) incorporate clinical, imaging, and laboratory parameters such as blood pressure (BP), right ventricular (RV) size on computed tomography angiography (CTA), echocardiographic evidence of RV dysfunction, and biomarker evidence of RV strain [ [1] Konstantinides S.V. Meyer G. Becattini C. et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur. Heart J. 2019; https://doi.org/10.1093/eurheartj/ehz405 Crossref Scopus (1145) Google Scholar ]. Although a subset of patients with PE who are initially stable experience acute decompensation and inpatient mortality, current risk stratification models are associated with only 21% positive predictive value for identifying this high-risk cohort [ [2] Jiménez D. Kopecna D. Tapson V. et al. Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism. Am. J. Respir. Crit. Care Med. 2014; https://doi.org/10.1164/rccm.201311-2040OC Crossref Scopus (131) Google Scholar ].

Management of submassive pulmonary embolism (PE) presents a quandary to the treating physician. A proportion of high-risk patients with submassive PE warrant aggressive therapy to reduce right ventricular (RV) strain and pulmonary artery pressures (PAP). Systemic thrombolytic therapy in patients with submassive PE is associated with a 2–3% risk of intracranial hemorrhage and remains controversial. However, anticoagulation often acts slowly, with the PEITHO trial demonstrating a 5% need for rescue thrombolysis among patients receiving anticoagulation alone [1].

Introduction Anomalous origin of coronary arteries has been observed in about 0.35-2.10% of the population. Patients with anomalous right coronary artery (ARCA) may present with significant symptoms, arrhythmias or ACS, and at times sudden death. Traditionally, surgical correction has been the recommended treatment. However, these may be technically challenging, and bypass grafting for such anomalies has the potential for graft failure because of competitive flow. We sought to determine the intermediate and long-term outcomes of drug-eluting stent placement for patients with symptomatic ARCA. We also looked at angiographic findings suggestive of interarterial course as confirmed by subsequent computed tomography (CT) findings. Methods Between January 2005 and December 2012, we enrolled 11 patients for elective percutaneous coronary intervention (PCI) of ARCA in a single center, prospective, nonrandomized fashion. Patients were followed up in clinic at 1 week, 3 months, 6 months, and 1 year, and then annually or more frequently if needed. All patients underwent a cardiac CT, as well as functional stress testing when needed to assess for recurrence of disease. Results All 11 of our patients, who presented with significant symptomatic stenosis with an ARCA, were successfully treated with PCI. Mean follow-up duration was 8.5 years. The only two deaths during follow-up were related to noncardiac causes (sepsis), with a mortality rate of 18.2%. Two patients had a positive functional study and on subsequent coronary angiography, one of them had significant in-stent restenosis (target lesion revascularization of 9.1%) and one distal to the stent (target vessel revascularization 9.1%). We found the observation of a "slit-like lesion" on angiography to have a sensitivity of 100% and specificity of 86% for the diagnosis of interarterial course of the anomalous vessel seen on subsequent CT. Conclusions Our study results suggest that PCI of ARCA is an effective and low-risk alternative to surgical correction, with good procedural success and long-term outcomes. It can provide symptomatic relief in such patients and may reduce the risk of sudden death in younger patients, without the inherent risks associated with surgical repair.

IntroductionOral factor Xa inhibitors such as Apixaban, betrixaban, edoxaban and rivaroxaban are widely used for the management of thrombotic and cardiovascular indications. A specific antidote namely andexanet alfa (AA) is approved for the management of bleeding complications with apixaban and rivaroxaban. The dosing regimen of andexanet alfa ranges from 400 – 800 mg bolus followed by 4 – 8 mg/min for up to two hours. This dosing regimen is projected to result in a circulating concentration of 75 – 150 ug/ml. This study is designed to compare the neutralization efficacy of andexanet alfa for various factor Xa inhibitors in clot‐based and anti‐Xa assays.Materials and MethodsCitrated pooled plasma (CPP) was prepared from individual donors. Active pharmaceutical ingredients (API) version of various factor Xa inhibitors were commercially obtained. Stock solutions of each of the agents were prepared at 1mg/ml and working concentrations at 100 and 10 ug/ml. Each of the factor Xa inhibitor was supplemented in plasma in the concentration range of 0 – 1 ug/ml. The neutralization profile of AA was studied at 100ug/ml and 200ug/ml and saline was used as a control. Clot‐based PT, aPTT and amidolytic anti‐Xa assays. The IC50 for the Xa inhibitory activity were calculated for the control drugs and after supplementation with AA. The neutralization profile in the clot‐based assays was measured in terms of decrease in clotting times.ResultsApixaban and edoxaban exhibited similar inhibitory profiles in the anti‐Xa assays, where as rivaroxaban and betrixaban exhibited much higher IC50s. AA effectively neutralized the anticoagulant effects of all agents at both the 100 and 200 ug/ml, however the neutralization profile in the clot based was not proportional to the anti‐Xa effects. At 200ug/ml only betrixaban was completely neutralized whereas all the other agents were partially neutralized. The order of neutralization at 200ug/ml was betrixaban > rivaroxaban > apixaban > edoxaban.ConclusionsThese studies show that the neutralization profiles of various Xa agents by AA exhibit differential characteristic response for each of the individual agent. These results indicate that individual dosing based on clinical endpoints for each agent rather than the neutralization of anti‐Xa activity measurement may be more relevant to the clinical outcome.

IntroductionSulodexide is a mucosal tissue derived glycosaminoglycan of mammalian origin which is clinically used in oral (capsule) and parenteral (ampules) forms for various clinical indications. The biologic potency of sulodexide is expressed in lipoproteinlipase releasing units (LSU). As a parenteral drug sulodexide produces sizable anticoagulant effects in various laboratory assays including the activated clotting time which is routinely used during surgical procedures. In comparison to heparin the USP referenced potency of sulodexide is reported to be 95 – 105 U/mg by anti‐Xa assay and 30 – 40 U/mg by anti‐IIa assay. The purpose of this study is to determine the whole blood anticoagulant effect of parenteral preparations of sulodexide and its neutralization by protamine sulfate.Materials and MethodsParenteral formulations (ampules) containing 600 LSU/2 ml were diluted with saline to make 10 and 100 LSU/ml working solutions. Protamine sulfate was obtained from the Loyola hospital pharmacy and diluted to 1.00 – 0.12 mg/ml. Anticoagulant effects of sulodexide over the concentration range of 1.0 – 0.25 LSU/ml were measured on the Hemachrom ACT instrument in freshly drawn normal human blood (n=5–10). Protamine neutralization studies were carried out at a fixed sulodexide level (1.0 LSU/ml) and variable protamine sulfate levels (50–12.5 μg/ml).ResultsSulodexide produced a concentration‐dependent anticoagulant effect in normal human whole blood over a concentration range of 0.25 – 1.0 LSU/ml in the range of (238 ± 24 to 401 ± 30 seconds) in comparison to saline control (136 ± 12 seconds). Protamine sulfate supplementation at a concentration range of 50 – 12.5 μg/ml produced varying levels of neutralization of the anticoagulant effects of sulodexide (1 LSU/ml). 50 μg/ml protamine completely neutralized sulodexide at 1 LSU/ml whereas at lower concentrations it partially neutralized the anticoagulant effects.DiscussionThe results demonstrate that sulodexide in parenteral formulation produces a strong anticoagulant effect as measured by whole blood ACT. At a concentration of 1.0 LSU/ml, sulodexide produces an anticoagulant effect that is comparable to that observed with surgical anticoagulation levels of heparin (>3 μg/ml). The anticoagulant effects of sulodexide are neutralized by protamine sulfate which can be used as an antidote for sulodexide.ConclusionParenteral (ampules) sulodexide can be used for anticoagulation in dose dependent fashion and protamine sulfate can be used as an antidote for this agent thus in the event of a shortage of unfractionated heparin sulodexide can be used as a substitute anticoagulant drug for the indications in which heparin is considered.

The incremental benefit of emergency medical services (EMS) activation of the cardiac catheterization laboratory (CCL) for ST-elevation myocardial infarction (STEM) in the setting of an established in-house interventional team (IHIT) is uncertain. We evaluated the impact of EMS activation on door-to-balloon (D2B) time and first medical contact-to-balloon (FMC2B) time for STEMI when coupled with a 24-hour/day IHIT. All patients presenting with STEMI to Loyola University Medical Center had demographic, procedural, and outcome data consecutively entered in a STEMI Data Registry. From 223 consecutive patients presenting between April 2009 and December 2015, a retrospective analysis was performed on 190 patients. Patients were divided into 2 groups depending on CCL activation mode (EMS activation or emergency department activation) and STEMI treatment process times were compared. The primary end point was D2B process times. The secondary end point was FMC2B process times in a subgroup analysis of EMS-transported patients. D2B times were shorter (37 +/- 14 minutes vs 57 +/- 27 minutes, p < 0.001) with EMS activation. Subgroup analysis of EMS-transported patients demonstrated shorter FMC2B times with EMS activation (52 +/- 17 minutes vs 67 +/- 32 minutes, p = 0.002). EMS activation was the only predictor of D2B <= 60 minutes in multivariable analysis of EMS-transported patients (odds ratio 9.4; 95% confidence interval 2.1 to 43.0; p = 0.04). In conclusion, EMS activation of the CCL in STEMI was associated with significant improvements in already excellent D2B and FMC2B times even in the setting of a 24-hour/day IHIT. (C) 2019 Elsevier Inc. All rights reserved.

Acute pulmonary embolism (PE) in the setting of a Patent Foramen Ovale (PFO) and clot-in-transit across the PFO poses a therapeutic dilemma. 64 year old male presented with acute dyspnea 3 weeks after ischemic stroke. CT PE-protocol revealed dilated right ventricle (RV) and proximal bilateral

Current risk models in acute Pulmonary Embolism (PE) have poor positive predictive ability and do not predict response to therapy. We sought to investigate the predictive power of Plasminogen Activator Inhibitor-1 (PAI-1) in acute PE. We analyzed patients who underwent evaluation by the Pulmonary

Background: At present, it is unclear whether right heart dysfunction (RHD) predicts adverse outcomes in patients with severe mitral regurgitation (MR) after transcatheter mitral valve repair. Methods: 74 consecutive patients treated with MitraClip at our institution were included in the analysis. Right heart catheterization (RHC) hemodynamics were assessed to determine right atrial pressure (RAP), right ventricular diastolic pressure (RVDP), RV +dP/ dT, RV systolic pressure (RVSP), mean pulmonary artery pressure (MPAP), right ventricular failure index (RVFI, ratio of RAP to pulmonary capillary wedge pressure (PCWP)), and pulmonary vascular resistance (PVR). Transthoracic echocardiograms were reviewed to determine RA volume index (RAVI), severity of tricuspid regurgitation (TR), RV diameter, tricuspid annular plane systolic excursion (TAPSE), DTI-derived tricuspid lateral annular systolic velocity (RV S'), severity of pulmonic regurgitation (PR), RVSP, PASP, and RFVI. Cox proportional hazard models were utilized to examine the relation between variables and mortality. Results: The median STS risk was 10%. RAP >15 mmHg (HR: 4.1, 95%CI: 1.1-16), RVDP >10 mmHg (HR: 13, 95%CI: 2.5-67), MPAP >40mmHg (HR: 3.5, 95% CI: 1.03-12), RVFI (RA/PCWP) >0.63 (HR: 3.0, 95%CI: 1.04-8.5), and PVR >3 Woods units (HR: 3.5, 95% CI: 1.2-10.1) were significantly associated with increased risk of death. In contrast, none of the echocardiographic variables were predictive of death after MitraClip. Conclusions: Invasively measured reduced RV systolic function (elevated RFVI (RA/PCWP)), elevated RH filling pressures (RAP and RVDP), and pulmonary artery hypertension (elevated MPAP and PVR) may identify patients with severe MR undergoing MitraClip who are at increased risk of adverse outcomes.

Heparin, an anticoagulant widely used in numerous medical applications, is considered an essential medicine by the WHO. Due to its high volume use and that it is the parent material for low molecular weight heparins, there is potential for the raw material to be in short supply. The African swine fever epidemic in China, ongoing since August 2018, has added further restraints on heparin source material supply. At present medical grade heparin in the US is only derived from porcine intestinal mucosa; however, there are explorations into using bovine, ovine, and other sources. Bovine heparin, once common place in the US pharmaceutical sector, is again under consideration by the US FDA. This study focused on the primary immunogenic activity associated with heparin, that is heparin-induced thrombocytopenia (HIT), and how the interaction of bovine heparin with functional HIT antibodies compares to that of porcine heparin. Materials and Methods Bovine unfractionated heparin from multiple manufacturers was compared to commercial medical grade porcine heparin obtained from US pharmacies. The US Pharmacopeia porcine heparin standard was used to determine potency equivalence. Antibodies to the complex of platelet factor 4/heparin (PF4/heparin) from banked clinically confirmed HIT patient apheresis fluids were combined with heparin and donor platelet rich plasma (PRP; blood collected in citrate from volunteers after signing a consent document). Heparins were tested at final concentrations of 0.1, 0.4, 0.8, 1, and 100 U/mL. The platelet activation response was determined on the BioData PAP-8 Platelet Aggregometer and quantitated in terms of primary slope (PS), area under the curve (AUC), maximum aggregation (MA), and final aggregation (FA). Characterization of the biophysical interaction between varying molar ratios of human PF4 and heparin was performed using photon correlation spectroscopy (PCS) and zeta potential (Zp) measurements of PF4/heparin complexes using Zetasizer Nano ZS instrumentation and software. Differences between bovine and porcine heparin were assessed by t-test or Mann-Whitney test. Concentration-response curves were analyzed by two-way ANOVA followed by the Holm-Sidak multiple comparison test using SigmaPlot software. Results Platelet activation to PF4/heparin antibodies at bovine and porcine heparin concentrations of 0.1 U/mL (56 ± 9 % vs. 54 ± 11 % MA) and 0.4 U/mL (59 ± 10 % vs. 65 ± 8 % MA) were the same with the expected inhibition (9 ± 4% MA) at the supra-therapeutic concentration of 100 U/mL. Consistent responses were obtained across 21 lots of bovine heparin, 30 lots of porcine heparin, and 38 platelet-HIT antibody combinations. The HIT potential of bovine heparin and porcine heparin was not statistically different (p>0.05). At higher medical use doses, the platelet aggregation response in the presence of HIT antibodies was actually lower for bovine heparin than porcine heparin (0.8 U/mL, 49 ± 10 % vs. 64 ± 9 % MA, p<0.05; and 1.0 U/mL, 45 ± 11 % vs. 62 ± 9 % MA, p<0.05). By PCS, it was observed that the maximal aggregation between PF4 and either porcine or bovine heparin occurred at comparable molar ratios (7.3 ± 1.5 vs. 6.4 ± 0). Although the porcine and bovine heparins exhibited comparable molecular weights (16,333 ± 153 vs. 16,790 ± 230 Da) and polydispersities (1.19 ± 0.02 vs. 1.15 ± 0.01), porcine heparin formed somewhat larger complexes with PF4 (1113 ± 65 nm) than did bovine heparin (863 ± 68 nm). The molar ratios of PF4 to heparin at which the charge of the complex was fully neutralized (Zp = 0) was comparable for porcine and bovine heparin (9.04 ± 0.19 vs. 9.97 ± 0.65). Consistent responses were obtained across 4 lots of bovine heparin and 3 lots of porcine heparin. Conclusions Bovine heparin and porcine heparin had the same in vitro functional platelet activation response in the presence of HIT antibodies, the same potential to form complexes with human PF4, and the same associated features that make PF4 immunogenic. This investigation demonstrates that bovine heparins should have a similar immunogenic response as porcine heparin at equi-unit dosing. Current refinements in the manufacturing process for bovine and porcine heparins have led to well-characterized and purified products which is reflected in their comparable biological behavior. Disclosures No relevant conflicts of interest to declare.