History Of Gastrointestinal Bleeding Research Articles

A Multicenter Study of Safety, Tolerability, and Effectiveness of Antithrombotic Therapy in Hereditary Hemorrhagic Telangiectasia

Introduction: With a prevalence of 1 in 5000 persons, hereditary hemorrhagic telangiectasia (HHT) is the second-most common hereditary bleeding disorder in the world. As HHT is a bleeding disorder with a concomitant elevated thrombotic risk, antithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed, but data describing its use is extremely limited. Antithrombotic therapy recommendations in the recently published Second International HHT Guidelines are based on this very limited data (largest prior cohort study including 28 patients) or expert opinion alone. Methods: We evaluated outcomes in a 5-hospital observational cohort study of adults with HHT receiving antithrombotic therapy over a 26-year period. Patients were identified via electronic database query, and eligibility was confirmed and data collection performed via manual chart review. Multivariable logistic modeling was used to assess for predictors of premature antithrombotic therapy discontinuation and hematologic characteristics and healthcare utilization before and after initiation of antithrombotic therapy were evaluated using paired t-tests (continuous data) and chi-square tests (categorical data). Results:Patients and Episodes: 119 HHT patients with 187 discrete antithrombotic therapy episodes were included. Median (range) age was 70 (27-92) years and 69 patients (58%) were female. Most common antithrombotic indications were venous thromboembolism (61 episodes), coronary artery disease (29 episodes), and atrial fibrillation (29 episodes). Most common antithrombotic agents used (by number of episodes) were aspirin (57), warfarin (35), low molecular weight heparin (26), apixaban (15), rivaroxaban (8), and multiple simultaneous medications (41). Tolerability and Effectiveness Overall and by Antithrombotic Therapy Class: 59 patients (50%) prematurely discontinued and/or dose-reduced therapy (including 52 patients [44%] who discontinued) due to worsening bleeding. Initiation at reduced dose-intensity had a similar premature discontinuation rate (49%) as initiation at standard dose-intensity (43%). Difficulty receiving indicated therapy may have resulted in increased thromboembolic recurrence (20 patients, 17%). Rates of dose-reduction and/or premature discontinuation were similar regardless of anticoagulant class (warfarin, 46%; heparin-based, 48%; direct oral anticoagulant [DOAC], 44%) or with multiple simultaneous agents (44%) but slightly lower with single-agent antiplatelet therapy (37%). Predictors of Therapy Discontinuation: In a multivariable logistic model, a history of GI bleeding was associated with 3.25-fold odds of discontinuation (P=0.001, Figure). Adverse Events Associated with Antithrombotic Therapy: Hemoglobin was significantly lower (10.8 g/dL vs 12.2 g/dL, P<0.001), and need for intravenous iron and RBC transfusion significantly higher (29 patients vs 12 patients, P=0.004), in the 3 months after antithrombotic therapy initiation versus the 3 months before (Table); number of patients requiring ED visits and/or hospital admissions due to bleeding also increased. 75 patients (63%) developed worsened epistaxis (of whom 33% dose-reduced or discontinued antithrombotic therapy due to epistaxis) and 44 patients (37%) developed newly-diagnosed or worsened gastrointestinal bleeding (of whom 59%, dose-reduced or discontinued antithrombotic therapy due to GI bleeding). Conclusions: Successful administration of antithrombotic therapy is challenging in HHT, resulting in objectively higher morbidity and healthcare utilization from worsened bleeding. Discontinuation rates approached 50% regardless of dose-intensity at initiation or type of antithrombotic agent used and were higher in patients with a history of gastrointestinal bleeding. These findings, from the largest and most comprehensive evaluation of antithrombotic therapy in HHT to date, challenge at least two recommendations made based on limited prior data or expert opinion alone in the Second International HHT Guidelines: the recommendation for use of warfarin or heparin-based therapy over DOACs and the avoidance of multiple simultaneous agents even when otherwise indicated due to concern for higher bleeding risk. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure.

Transcatheter left atrial appendage closure (LAAC) is performed in patients unsuitable for long-term anticoagulation, predominantly due to prior bleeding events. The study aimed to investigate the incidence and predictors of clinically significant bleeding (CSB) post-LAAC. Consecutive patients after LAAC with an Amplatzer or WATCHMAN device were analyzed (05.2014-11.2019). Bleeding was classified as CSB when associated with at least one of the following: death, ≥2 g/dL hemoglobin drop, ≥2 blood units transfusion, critical anatomic site, or hospitalization/invasive procedure. Among 195 patients (age 74 (68-80), 43.1% females, HAS-BLED score 2.0 (2.0-3.0)), during median follow-up of 370 (IQR, 358-392) days, there were 15 nonprocedural CSBs in 14 (7.2%) patients. Of those, 9 (60.0%) occurred during postprocedural dual antiplatelet therapy (DAPT) (median 46 (IQR: 16-60) days post-LAAC) vs. 6 (40%) after DAPT discontinuation (median 124 (81-210) days post-LAAC), translating into annualized CSB rates of 14.0% (per patient-year on DAPT) vs. 4.6% (per patient-year without DAPT). In 92.9% (13/14) of patients, the post-LAAC nonprocedural CSB was a recurrence from the same site as bleeding pre-LAAC. In the multivariable model, admission systolic blood pressure (SBP) > 127 mmHg (HR = 10.73, 1.37-84.26, p = 0.024), epistaxis history (HR = 5.84, 1.32-25.89, p = 0.020), permanent atrial fibrillation (AF) (HR = 4.55, 1.20-17.20, p = 0.025), and prior gastrointestinal bleeding (HR = 3.35, 1.01-11.08, p = 0.048) predicted post-LAAC CSB. Nonprocedural CSBs after LAAC, with a similar origin as the pre-LAAC bleedings, were observed predominantly during postprocedural DAPT and predicted by elevated admission SBP, prior epistaxis, permanent AF, and gastrointestinal bleeding history. Whether a more reserved post-LAAC antiplatelet regimen and stringent blood pressure control may improve LAAC outcomes remains to be studied.

Clinical Case 26—Is it possible to live with thrombosed left ventricular assist device (LVAD)?

Abstract LVAD HeartWare was implanted in a 63-year-old patient with end-stage dilated cardiomyopathy. The postoperative course was complicated by massive gastrointestinal (GI) bleeding that required surgical exploration of the GI tract. For the next 1.5 years, the patient has significantly improved functional capacity with proper LVAD function. A month before the incident, an alarm indicating a pump malfunction was recorded. The patient presents with congestive symptoms and an altered sound of LVAD. Laboratory indicates seven times elevated LDH values, low HGB and INR 3.03. Thrombophilia tests were negative. Echo examination does not indicate pump thrombosis, but the pump parameters show increased energy consumption (&amp;gt;6 W) and increased flow (&amp;gt;7 L/min). A diagnosis of LVAD thrombosis was made. Fibrinolytic therapy was contraindicated because of a history of GI bleeding, so a continuous infusion of heparin was started. Despite this, the patient's clinical condition deteriorates, and a decision was made to discontinue the LVAD, to prevent further hemolysis that led to acute kidney injury (AKI). The procedure was performed without endangering the patient. Massive hemolysis, however, leads to the progressive development of AKI requiring CVVHDF. Global respiratory insufficiency develops and mechanical ventilation was started. After six days of intensive treatment, the patient recovered and was discharged home with a thrombosed pump. For the next 2.5 years, the patient was in satisfactory condition during follow-ups, the pump was not explanted. Even sophisticated medical devices carry with them risks for the patient's life despite adequate management. Treatment of LVAD thrombosis depends on patient characteristics and pump-related factors.

Protective effect of proton pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis

Abstract Background The concurrent use of proton pump inhibitor (PPI) in oral anticoagulant (OAC) treated patients may be associated with a lower risk of gastrointestinal bleeding (GIB), but evidence is still conflicting according to individual OACs. Purpose We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI co-therapy. Methods A systematic search of PubMed, EMBASE, and Cochrane was performed for studies reporting GIB risk in OAC and PPI co-therapy. Primary outcomes were total GIB and major GIB events. We calculated pooled estimates of GIB risk by a random-effect meta-analysis and reported as odds ratios (OR) and 95% CI. Stratified analyses according to the origin of GIB, ethnic groups, individual OACs, and the presence of underlying GIB risk factors were performed. Results A total of 10 studies (1 randomized controlled study and 9 observational studies) and 1,970,931 patients who received OAC were included. OAC and PPI co-therapy were associated with a lower risk of total GIB, and major GIB; OR (95% CI) was 0.67 (0.62–0.74) for total GIB and 0.68 (0.63–0.75) for major GIB, respectively. Among total GIB, only the risk of upper GIB was lower with OAC and PPI co-therapy (OR 0.67, 95% CI 0.64–0.70). No difference in the lower risk of primary GIB outcomes of PPI co-therapy was observed between Asians and non-Asians (p-for-difference, total GIB=0.695, major GIB=0.748, respectively) and among individual OACs except for edoxaban. The protective effect of PPI on total GIB was more significant in high-risk patients, defined as those with concurrent medication of antiplatelets or non-steroidal anti-inflammatory drugs (OR 0.62, 95% CI 0.52–0.73) and presence of high bleeding risk factors such as previous GIB history, HAS-BLED score ≥3, or underlying gastrointestinal diseases. (OR 0.65, 95% CI 0.61–0.70). Conclusion In patients who receive OAC, the use of PPI co-therapy was associated with a lower risk of total GIB and major GIB irrespective of ethnic group and OAC type except for edoxaban. PPI co-therapy can be considered particularly in patients on concomitant NSAID and antiplatelet use or patients with high GIB risk factors. Funding Acknowledgement Type of funding sources: None.

S3054 Interdisciplinary Management of a Complicated Pregnancy in a Patient With Cirrhosis

Introduction: We present a unique case of clotting disorder related cirrhosis leading to pregnancy complications. Case Description/Methods: A 29-year-old Caucasian female with a history of gastrointestinal bleeding, gastroesophageal reflux disease, epistaxis, and alcohol use disorder, goes for a routine gynecologic checkup when the physician notices a concerning enlargement of the caudate lobe on a computed tomography scan. Further evaluation reveals cirrhosis and Budd-Chiari syndrome. The patient starts enoxaparin and warfarin following this diagnosis. Eventually the patient is placed on the liver transplant list with a MELD (model of end-stage liver disease) score of 17 which improves to a score of 7 with sobriety. The patient attempts pregnancy and is unable to conceive. She is told she has early menopause at the age of 34. She undergoes reproductive endocrinology evaluation and achieves a successful in-vitro fertilization with a donor egg at age 36. This starts her high-risk pregnancy. The high-risk nature of this pregnancy revolves around the patient’s complicated past medical history of hemorrhagic stroke of unclear etiology, cirrhosis complicated by esophageal variceal bleeding, coagulopathy, Budd-Chiari syndrome, and thrombocytopenia. The patient has close variceal and hepatic vein thrombosis surveillance, labs, and routine checkup for vaginal bleeding with her increased risk of thrombosis during pregnancy. Endoscopy in the 1 st and 3rd trimesters shows small esophageal varices with no evidence of progression. Abdominal ultrasound displays vasa previa at approximately 28 weeks with velamentous umbilical cord insertion 2.3 cm from the internal os. After careful monitoring, the vasa previa is noted to resolve with umbilical cord insertion increasing to 4.8 cm from internal os in the following weeks. Repeated fetal echocardiograms present concern for the fetus being large for gestational age with estimated fetal weights ranging between the 95th-98th percentiles. The patient undergoes elective cesarean delivery and gives birth to a baby boy at 34 weeks with no labor complications. Discussion: We present a unique case of pregnancy during cirrhosis requiring management with multiple specialists. Although the physiologic changes in pregnancy are well understood, the way in which cirrhosis affects pregnancy and its outcomes are not yet well understood given paucity of published data. Certainly, there is complex interplay and physiology involved with increased potential for pregnancy complications.

Low Body Mass Index without Malnutrition Is an Independent Risk Factor for Major Cardiovascular Events in Patients with Hemodialysis.

We retrospectively analyzed major cardiovascular events (MACE), a composite of cardiac death, nonfatal myocardial infarction, unplanned revascularization, heart failure leading to hospitalization, and stroke during a 3-year follow-up of patients with hemodialysis at the dialysis center of our general hospital that can treat comprehensive diseases. Moreover, we conducted an exploratory study that focuses on the risk factor for MACE in patients with hemodialysis.A total of 132 patients with hemodialysis at our dialysis center as of June 2017 were included in the study. Data on event incidence, including death and various clinical indicators, were collected in the electronic medical record for three years until June 2020. Between June 2017 and June 2020, of the 132 patients with hemodialysis, 31 patients experienced MACE (10 cardiovascular deaths, 3 nonfatal myocardial infarction, 11 unplanned revascularizations, 5 heart failure leading to hospitalization, and 2 stroke). The patients with MACE had a lower body mass index (BMI), longer duration of dialysis with more preexisting gastrointestinal (GI) bleeding, and took more aspirin compared to the MACE-free patients. Malnutrition markers (serum total protein, serum albumin, and serum total cholesterol) were similar in both groups. In a univariate analysis for MACE, the odds ratio was significantly higher for BMI < 18.5, duration of hemodialysis, and history of GI bleeding. Multivariable-adjusted odds ratios for MACE were significantly higher for BMI < 18.5.In conclusion, BMI < 18.5 without malnutrition may be an independent risk factor for MACE in patients with hemodialysis.

Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: A systematic review and meta-analysis.

The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy. A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random-effect meta-analysis and reported as odds ratios and 95% confidence interval. A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62-0.74) for total and 0.68 (0.63-0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non-Asians (P-for-difference, total GIB = .70, major GIB = .75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24-44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti-inflammatory drug users and those with high bleeding risks: patients with previous GIB history, HAS-BLED ≥3 or underlying gastrointestinal diseases. In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.

INTERBLEED: Design of an International Study of Risk Factors for Gastrointestinal Bleeding and Cardiovascular Events After Gastrointestinal Bleeding

BackgroundBleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding. MethodsINTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months. ResultsAs of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls. ConclusionsKnowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications.

Gastrointestinal bleeding preceding new-onset atrial fibrillation - results from the nationwide FinACAF study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District Funding The Finnish Foundation of Cardiovascular Research Introduction Initiation of oral anticoagulation (OAC) in case of a new-onset atrial fibrillation (AF) requires assessment of bleeding history. Gastrointestinal (GI) bleedings are among the most common bleeding events. Purpose We aimed to assess clinical characteristics and initiation of OAC in patients with new-onset AF and a history of previous GI bleeding. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide study among AF patients conducted as a retrospective register-based linkage study combining data from several Finnish health care registers. The study population consists of all patients diagnosed with AF between the years 2010-2018 and with laboratory data available. Patients were identified from nationwide primary care and reimbursement registries and hospitalization records. OAC purchases at 90 days from cohort entry were obtained from the National Prescription Register upheld by the Social Insurance Institution of Finland. Results 134 242 patients from the initial FinACAF cohort were included in this substudy. Of these, 6543 (4.9%) patients had a history of GI bleeding. Those with GI bleeding were more often male (52.6%), older (mean age 76.6 ± 11.4 vs 72.4 ± 13.1 years), and had more comorbidities. They also had lower blood hemoglobin (mean 124.9 ± 21.3 vs 135.8 ± 18.4 g/l) and higher serum creatinine (mean 99.7 ± 75.8 vs 87.5 ± 52.7 µmol/l) levels than patiens without preceding GI bleeding. Furthermore, initiation of OAC medication was less frequent in the GI bleeding group (46.9% vs 58.6%). Patient characteristics of the study population including age, sex, comorbidities, OAC medication and laboratory findings are shown in Figures 1 and 2. Conclusions Patients with AF and preceding GI bleeding are vulnerable to rebleeding events. This may affect decision-making of clinicians, leading to more infrequent initiation of OAC medications.

Improvement in gastrointestinal bleeding after septal myectomy for hypertrophic cardiomyopathy

ObjectivePatients with obstructive hypertrophic cardiomyopathy may have occult gastrointestinal bleeding. In this study, we analyzed outcomes of septal myectomy in patients who had a history of gastrointestinal bleeding preoperatively to understand patient characteristics and impact of septal reduction on recurrent gastrointestinal bleeding. MethodsWe analyzed 73 adult patients who had a history of gastrointestinal bleeding before transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and compared outcomes to 219 patients without gastrointestinal bleeding preoperatively. ResultsPatients with preoperative history of gastrointestinal bleeding were older (median (IQR) age, 65 (59-69) years, P < .001) and were more likely to have systemic hypertension (70% vs 53%, P = .020) and coronary artery disease (25% vs 13%, P = .026). Preoperatively, patients with gastrointestinal bleeding had a larger left atrial volume index (median, 53 mL/m2; interquartile range, 42-67; P = .006) and greater right ventricular systolic pressure (median, 36 mm Hg; interquartile range, 32-49; mm Hg, P = .005) but no significant difference in severity of outflow tract obstruction (P = .368). There were no perioperative deaths. The estimated 5- and 10-year survivals were 96.6% and 81.8%, respectively. At a median of 3.4 (interquartile range, 1.9-9.1) years after septal myectomy, 11 patients (15%) had recurrence of gastrointestinal bleeding, which was attributed to angiodysplasia or unknown causes in 6 patients (8%). ConclusionsPatients with a preoperative history of gastrointestinal bleeding have favorable short- and long-term outcomes after septal myectomy for obstructive hypertrophic cardiomyopathy. Remission of gastrointestinal bleeding was observed in 85% of patients postprocedure, and only 8% of the patients had recurrent gastrointestinal bleeding due to angiodysplasia or unknown causes.

Direct oral anticoagulants versus warfarin in nonvalvular atrial fibrillation patients with prior gastrointestinal bleeding: a network meta-analysis of real-world data.

The objective of present study was to compare the safety and efficacy of resuming direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and prior gastrointestinal bleeding (GIB). PubMed, Embase, Web of Science, and the Cochrane Library were searched from their inception until 2 June 2021 for observational cohort studies in patients with AF, who resumed VKAs or DOACs after a history of GIB. Studies that reported data on clinical outcomes including risk of recurrent GIB, thromboembolic events, or all-cause mortality were included. A network meta-analysis was performed to calculate the pooled hazard ratio (HR) and associated 95% credible intervals (CIs), using a random effects model in a Bayesian framework. A total of 10 studies were included in the final analysis, including 59,244 AF patients with prior GIB, of whom 27,793 resumed DOACs, 24,635 resumed warfarin, and 6816 did not resume anticoagulation. Compared with no resumption of anticoagulation, resumption of warfarin was associated with an increased risk of recurrent GIB (HR 1.33, 95% CI: 1.06-1.70), but no increased risk of recurrent GIB was found with resumption of DOACs (HR 1.22, 95% CI: 0.88-1.71); among individual DOACs, only rivaroxaban was associated with an increased risk of recurrent GIB (HR 1.67, 95% CI: 1.16-2.65). Compared with no resumption of anticoagulation, resumption of DOACs and warfarin was associated with a significant reduction in all-cause mortality (HR 0.57, 95% CI: 0.40-0.84; HR 0.58, 95% CI: 0.44-0.79), but no statistically significant reduction in thromboembolic events (HR 0.69, 95% CI: 0.4-1.2; HR 0.83, 95% CI: 0.55-1.29). In AF patients with prior GIB, resumption of DOACs may be safer, except for rivaroxaban.

Endovascular occlusion of the left atrialaud in patients with atrial fibrillations. Experience of city hospital

Background. Endovascular occlusion of the left atrial appendage (LAA) using the Watchman device may be considered an adequate alternative to oral anticoagulant (OAC) administration in high-risk patients.Objective. To describe our experience with Watchman endovascular occlusion of the left atrial appendage in a city hospital setting in terms of feasibility and safety, as well as assess the short-term efficacy of this procedure.Design and methods. The study included patients who underwent implantation of the Watchman occlusion device from January 2016 to November 2020. The effectiveness of the procedure was defined as the ability to implant the Watchman without maintaining residual current, safety was defined as the occurrence of nosocomial and 45-day events including stroke, pericardial effusion, major bleeding, and device migration.Results. The study included 22 patients: 10 men and 12 women, who underwent implantation of the Watchman occluding device in the LAA. The indication for implantation was a history of gastrointestinal bleeding in 15 patients, cerebral hemorrhage in 3 patients and low compliance to therapy in 4 patients. The success rate of the procedure was 95.7 %. According to control transesophageal echocardiography, after 45 days LAA was excluded from the bloodstream in 21 of 22 patients.Conclusion. Despite the higher complication rate of occlusion of the LAA compared to drug treatment, the overall mortality from any cause in patients with the implanted Watchman was lower.

Rate of transesophageal echocardiography related complications during 1229 TEE-guided structural heart disease procedures

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction: Transesophageal echocardiography (TEE) has long provided excellent diagnostic imaging of left-sided valvular pathology with an excellent safety profile; however, recent data has suggested an increased risk of injury related to TEE guidance. Purpose This study aims to evaluate the incidence and nature of TEE-related oropharyngeal or esophageal complications in patients undergoing TEE-guided structural heart procedures and identify associated risk factors. Methods We reviewed consecutive patients undergoing TEE-guided structural heart procedures from 2005-2020. All procedures were performed under general anesthesia. TEE-related oropharyngeal or esophageal complications were defined as those occurring within 30 days of the procedure resulting in i) persistent dysphagia, odynophagia, or upper gastrointestinal bleeding requiring prolonged endotracheal intubation, therapeutic endoscopic or surgical intervention, or diagnostic imaging that demonstrated oropharyngeal or esophageal injury. ii) upper gastrointestinal bleed requiring transfusion, hemodynamic compromise warranting mechanical or pharmacologic support; or iii) oropharyngeal or esophageal complications leading to death. For multivariate analysis, all variables with a p &amp;lt; 0.15 at univariate analysis were included in the model. Results Among 1229 adult patients undergoing TEE-guided structural heart procedures between 2005-2020, 274 underwent a transcatheter aortic valve replacement (TAVR) with the remaining 955 undergoing either mitral valve transcatheter edge-to-edge repair (mTEER, n = 278), mitral paravalvular leak closure (PVLC, n = 354), mitral valve-in-valve replacement (VIV, n = 41), or left atrial appendage closure (LAAO, n = 282). Of these, 6 (0.5 %) had TEE-related complications; 0% TAVR, 0% VIV, 0.36% LAAO, 0.28% PVLC, 1.41% mTEER (p = 0.14). Of the six patients with complications 3 required at least one day of prolonged tracheal intubation and one a blood transfusion. None required surgical repair. Factors associated with increased complication risk (Table) included a prior history of gastrointestinal bleed (Odds ratio 5.44 [0.98-30.04; p = 0.05]) and longer procedural time (OR per 30 min 1.15 [1.01-1.31, p = 0.03]). Patients undergoing mTEER had an increased risk of complication (OR 6.76 [1.23-37.1 p = 0.03]) and longer procedural time (OR per 30 mins 1.15[1.01-1.31, p = 0.04]) compared to other all other procedures. Conclusion(s): In a large series of patients undergoing cardiac structural interventions under general anesthesia with TEE-guidance, rates of TEE-induced injury were low. Risk of oropharyngeal or esophageal complications was increased with longer procedure times, prior gastrointestinal bleeding history, increased age, increased pre-procedural creatinine, procedural type being mTEER and in male patients, lower height. Abstract Table

Safety and efficacy of durvalumab plus bevacizumab in unresectable hepatocellular carcinoma: Results from the phase 2 study 22 (NCT02519348).

436 Background: The phase 2 Study 22 trial (NCT02519348) investigated durvalumab (anti-programmed cell death ligand-1 [PD-L1] antibody) and tremelimumab (anti-cytotoxic T-lymphocyte associated antigen 4 antibody) as monotherapy, or durvalumab in combination with tremelimumab or bevacizumab (anti-vascular endothelial growth factor [VEGF] antibody), for the treatment of patients with unresectable hepatocellular carcinoma (uHCC). Results of Study 22 that evaluated durvalumab and tremelimumab as monotherapy or in combination were reported previously. PD-L1 inhibition plus VEGF inhibition with bevacizumab may exhibit an additive effect to improve clinical activity. Herein, we report results from a single-arm cohort of Study 22, evaluating durvalumab plus bevacizumab as first-line treatment in patients with uHCC. Methods: Patients with uHCC who had not received any prior systemic therapy were administered durvalumab 1120 mg plus bevacizumab 15 mg/kg once every 3 weeks. Adequate endoscopic therapy according to institutional standards was required for patients with a history of gastrointestinal bleeding for &gt;12 months or those at high risk for esophageal varices. The primary endpoint was safety. Secondary endpoints included confirmed objective response rate (ORR; assessed by blinded independent central review [BICR] according to RECIST v1.1), duration of response (DoR; RECIST v1.1 by BICR) and overall survival (OS). Results: At the data cut-off (November 6, 2020), 47 patients were allocated to receive treatment. Median total treatment duration was 6.2 months (durvalumab) and 4.1 months (bevacizumab). Thirty-three (70.2%) patients experienced an adverse event possibly related to treatment (TRAE). Grade 3 or 4 TRAEs occurred in 4 (8.5%) patients; serious TRAEs occurred in 5 (10.6%) patients, including gastric ulcer perforation, ascites, and liver tumor rupture, possibly related to bevacizumab, and raised creatinine and pneumonitis, possibly related to durvalumab. There were 3 (6.4%) discontinuations and no deaths associated with TRAEs. Objective responses (RECIST 1.1 by BICR) were confirmed in 10 patients (ORR, 21.3%; 95% CI, 10.7–35.7); median DoR (RECIST 1.1 by BICR) was not reached. Median OS was not reached (95% CI, 12.52 months–non-estimable). Conclusions: Durvalumab plus bevacizumab was well tolerated and showed promising clinical activity in patients with uHCC. Durvalumab with or without bevacizumab in combination with transarterial chemoembolization is being investigated as locoregional therapy in patients with HCC not amenable to curative treatment in the phase 3 EMERALD-1 study (NCT03778957), and durvalumab with or without bevacizumab is being investigated in patients with HCC at high risk of recurrence after curative treatment in the phase 3 EMERALD-2 study (NCT03847428). Clinical trial information: NCT02519348.

Therapeutic decisions in a cohort of patients with idiopathic pulmonary fibrosis: a multicenter, prospective survey from Poland.

Background:Pirfenidone and nintedanib are considered as the standard of care in idiopathic pulmonary fibrosis (IPF), but there is no consensus as to which of these two agents should be regarded as first-line treatment.Objective:To provide real-world data on therapeutic decisions of pulmonary specialists, particularly the choice of the antifibrotic drug in patients with IPF.Methods:This was a multicenter, prospective survey collecting clinical data of patients with IPF considered as candidates for antifibrotic treatment between September 2019 and December 2020. Clinical characteristics and information on the therapeutic approach were retrieved. Statistical evaluation included multiple logistic regression analysis with stepwise model selection.Results:Data on 188 patients [74.5% male, median age 73 (interquartile range, 68–78) years] considered for antifibrotic therapy were collected. Treatment was initiated in 138 patients, while 50 patients did not receive an antifibrotic, mainly due to the lack of consent for treatment and IPF severity. Seventy-two patients received pirfenidone and 66 received nintedanib. Dosing protocol (p < 0.01) and patient preference (p = 0.049) were more frequently associated with the choice of nintedanib, while comorbidity profile (p = 0.0003) and concomitant medication use (p = 0.03) were more frequently associated with the choice of pirfenidone. Age (p = 0.002), lung transfer factor for carbon monoxide (TLCO) (p = 0.001), and gastrointestinal bleeding (p = 0.03) were significantly associated with the qualification for the antifibrotic treatment.Conclusion:This real-world prospective study showed that dose protocol and patient preference were more frequently associated with the choice of nintedanib, while the comorbidity profile and concomitant medication use were more frequently associated with the choice of pirfenidone. Age, TLCO, and history of gastrointestinal bleeding were significant factors influencing the decision to initiate antifibrotic therapy.

Improved perioperative mortality after secondary aortoenteric fistula repair and lessons learned from a 20-year experience

Secondary aortoenteric fistulas (SAEFs) are rare but represent one of the most challenging and devastating problems for vascular surgeons. Several issues surrounding SAEF treatment remain unresolved, including optimal surgical reconstruction and conduit choice. We performed an audit of our experience with SAEFs and highlight aspects of care that have affected outcomes over time with the intent to identify factors associated with best outcomes. We performed a single center, retrospective review of all consecutive SAEF repairs (1999-2019), defined as presence of a false communication between an enteric structure and pre-existing aortic graft. The primary endpoint was 30-day mortality. Secondary endpoints included incidence of complications and overall survival. Time-dependent outcome comparison was performed. Cox proportional hazards modeling and life-table analysis estimated risk and freedom from endpoints. A total of 57 patients (63% male; n= 36) presented with SAEF (median age, 69years; interquartile range [IQR], 61-74years). Median follow-up time was 10months (interquartile range, 3-21months. The most common presenting symptoms were gastrointestinal bleeding (60%; n= 34) and abdominal pain (56%; n= 3 2). For the overall cohort, 30% (n= 17) underwent extra-anatomic bypass with aortic ligation, 30% (n= 17) rifampin-soaked Dacron graft, 26% (n= 15) femoral vein (eg, neoaortoiliac system), and 14% (n= 8) cryopreserved aortic allograft. The enteric communication involved the duodenum in 85% (n= 48), and a double-layer hand-sewn primary repair was most commonly employed (61%; n= 35). Thirty-day mortality was 35% (n= 20) with no significant difference between 90days (39%; n= 22) and 180days (42%; n= 24). Morbidity was 70% (n= 40), with gastrointestinal (30%; n= 17; leak [9%]), pulmonary (25%; n= 14), and renal (21%) complications being most common. Incidence of reoperation for any vascular and/or gastrointestinal-related complication was 56% (n= 32). One-year and 3-year survival was 54%± 6% and 48%± 8%, respectively. Over time, 30- and 90-day mortality improved (odds ratio, 0.1; 95% confidence interval, 0.4-0.5; P= .002) despite no change in patient factors, operative strategy, conduit choice, or morbidity rate. Prehospital history of gastrointestinal bleeding was associated with worse survival (hazard ratio, 2.0; 95% confidence interval, 1.0-3.9; P= .06); however, reconstruction strategy (in-situ vs extra-anatomic bypass), postoperative gastrointestinal and/or vascular complication, omental flap use, and preoperative endovascular aneurysm repair history were not associated with outcome. In conclusion, we observed improved short-term mortality despite no significant change in patient presentation or postoperative complications. This highlights increasing institutional experience in selecting the optimal surgical strategy and improved ability to rescue patients experiencing adverse postoperative events. An individualized approach to reconstruction and conduit choice can lead to best outcomes after SAEF management when patients are treated at a high-volume aortic surgery center.

Gastric mucosa condition in patients with coronary artery disease and high risk of gastrointestinal bleeding (register REGATTA-1)

To assess the upper gastrointestinal mucosal condition by endoscopic and histological methods in patients with stable coronary arteries disease receiving long-term antiplatelet therapy with gastrointestinal bleeding (GIB) history or with high risk of this complication. The study included patients from the single-center prospective registry of long-term antithrombotic therapy REGATTA-1. The gastric mucosa endoscopic examination with biopsy was performed in 20 patients with gastrointestinal bleeding history less than 1 year ago and in 24 patients without GIB, which have concomitant risk factors such as erosions and ulcers history and/or persistent dyspepsia clinical signs. The mucosal condition (erosions and ulcers) was estimated using a modified Lanz scale. The presence of Helicobacter pylori was determined by Histological verification. The inflammatory process characteristics were evaluated according to the modified Sydney classification. All participants received antithrombotic therapy at the time of esophagogastroduodenoscopy; 81.8% of patients received proton pump inhibitors. Chronic inflammation (93.2%), atrophy (59.1%), multiple erosions (45.5%) or ulcers (18.2%) were the most frequent endoscopic finding. H. pylori infection, found in mucosal samples in 90.9% of patients was one of the most important pathogenesis mechanism, which support the gastrointestinal mucosa damage. Mucosal damage endoscopic signs remains despite long-term proton pump inhibitors therapy in patients with coronary arteries disease and concomitant GIB risk factors, receiving antithrombotic therapy. H. pylori contamination may be the cause of these changes. Therefore, its active screening and eradication is necessary in such patients.

Thrombotic events and rebleeding after hemorrhage in patients taking direct oral anticoagulants for non-valvular atrial fibrillation.

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

Abstract 9779: The Utility of Endoscopic Screening in Mitigating the Risk of Gastrointestinal Bleeding After Left Ventricular Assist Device Placement. A Retrospective Chart Review Study

Introduction: Left ventricular assist device (LVAD) is a lifesaving bridge to transplantation or destination therapy for patients with end-stage heart failure. More than one-third of patients suffer from gastrointestinal (GI) bleeding within one year of placement. We investigated the yield and safety of endoscopic screening for potential sources of GI bleeding before LVAD insertion. Hypothesis: Endoscopic screening prior to LVAD placement does not necessarily reduce the risk of GI bleed post LVAD. Methods: We performed a retrospective chart review study of patients at Saint Luke’s Mid America Heart Institute who underwent continuous-flow LVAD implantation from 2010 to 2020. Study participants were categorized based on whether or not they underwent screening endoscopy prior to LVAD implantation. Patients were followed for one year after implantation, and outcomes were collected to determine the yield and safety of these procedures. A multivariable logistic regression analysis was performed using SPSS® controlling for the following confounding factors: age, gender, race, and history of GI bleeding. Results: Among 205 patients with an LVAD, 169 patients were included in the study after excluding those with lack of data or those lost to follow up. 68 (40.23%) patients who received pre-LVAD screening by either upper and/or lower endoscopies, and 42 (24.85%) patients who had post-LVAD GI bleed. Patients who underwent pre-LVAD screening had similar rates of GI bleeding after LVAD compared to those who were not screened (odds ratio 1.66, 95% CI 0.648-4.264, P=0.2). Moreover, in patients with post LVAD GI bleed, endoscopy findings were typically different than those pre LVAD. No complications to the endoscopic interventions were reported. Conclusions: While endoscopic screening appears to be safe in patients before LVAD implantation, it had no association with GI bleeding risk or etiology after LVAD.

Our Approach and Review of Current Concepts of Catheter Directed Procedures in Acute Limb Ischemia

Acute lower limb ischemia (ALI) is defined as sudden reduction of limb perfusion, leading to a threat to viability of the extremity. With better access to technology and better training in endovascular management in peripheral arterial disease, catheter-directed procedures are an attractive and feasible option in ALI patients. This article deals with our approach to ALI, the basic guidelines and clinical pathway adopted for its management, the hardware and drugs used, and also intraoperative and postprocedural care. It also briefly delves into our experience in using this protocol as also the recent modifications to standard techniques that have been employed, keeping in mind drawbacks such as bleeding and failure of recanalization when employing standard procedures. All patients who presented with ALI from the period of June 2016 to May 2021 with a short history of symptoms &lt;14 days, Class 1, 2a, 2b ALI, and those that were fit and adequately consented for the procedure were studied. Those with age over 80 years, history of gastrointestinal bleed, and history of central nervous system bleed in the last 30 days were automatically excluded from undergoing these procedures. During this period, we saw 112 ALIs in our department, of which 74 cases were primarily deemed suitable for catheter-directed procedures, 60 for catheter-directed thrombolysis, 6 for AngioJet™, and 8 using the CAT6 Penumbra™ catheter. 6 (8.1%) cases subsequently failed the procedure and were converted to open surgery, of which only 2 of 6 had limb/s salvaged, meaning that 4 of 6 converted cases had major amputations. The high amputation rates (25 out of 112, i.e. 22.32%) were clearly attributable on audit, to a delayed referral to a tertiary care center, leading to a large number of Class 3 cases. In our part of the world, open surgical embolectomy is still the mainstay of treatment for ALI. However, an endovascular approach is an option that may be used in selected cases. The structural, personal, and technical conditions of each department must be considered before advocating this modality for therapy in patients.