Half-Dose Direct Oral Anticoagulation Versus Standard Antithrombotic Therapy After Left Atrial Appendage Occlusion

ObjectivesThis study evaluated the long-term efficacy of a standard antithrombotic strategy versus half-dose direct oral anticoagulation (DOAC) after Watchman implantation.BackgroundNo consensus currently exists on the selection of the most effective antithrombotic strategy to prevent device-related thrombosis (DRT) in patients undergoing endocardial left atrial appendage closure.MethodsAfter successful left atrial appendage closure, consecutive patients were prescribed a standard antithrombotic strategy (SAT) or long-term half-dose DOAC (hdDOAC). The primary composite endpoint was DRT and thromboembolic (TE) and bleeding events.ResultsOverall, 555 patients (mean age 75 ± 8 years, 63% male; median CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category] score 4 [interquartile range (IQR): 3-6]; median HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] score 3 [IQR: 2-4]) were included. Patients were categorized into 2 groups (SAT: n = 357 vs hdDOAC: n = 198). Baseline clinical characteristics were similar between groups. The median follow-up duration was 13 months (IQR: 12-15 months). DRT occurred in 12 (2.1%) patients, all in the SAT group (3.4% vs 0.0%; log-rank P = 0.009). The risk of nonprocedural major bleeding was significantly more favorable in the hdDOAC group (0.5% vs. 3.9%; log-rank P = 0.018). The rate of the primary composite endpoint of DRT and TE and major bleeding events was 9.5% in SAT patients and 1.0% in hdDOAC patients (HR: 9.8; 95% CI: 2.3-40.7; P = 0.002).ConclusionsAfter successful Watchman implantation, long-term half-dose DOAC significantly reduced the risk of the composite endpoint of DRT and TE and major bleeding events compared with a standard, antiplatelet-based, antithrombotic therapy.     

Prophylactic Rivaroxaban Therapy for Left Ventricular Thrombus After Anterior ST-Segment Elevation Myocardial Infarction

ObjectivesThe aim of this study was to investigate the effects of rivaroxaban on left ventricle thromboprophylaxis in patients with anterior ST-segment elevation myocardial infarction (STEMI).BackgroundAnterior STEMI is associated with an increased risk of left ventricular thrombus (LVT) formation. The contemporary role of prophylactic rivaroxaban therapy remains unclear.MethodsWe randomly assigned 279 patients with anterior STEMI who had undergone primary percutaneous coronary intervention to receive, in a 1:1 ratio, low-dose rivaroxaban (2.5 mg twice daily for 30 days) and dual antiplatelet therapy (DAPT) or only DAPT. The primary efficacy outcome was the LVT formation within 30 days. Net clinical adverse events were assessed at 30 days and 180 days, including all-cause mortality, LVT, systemic embolism, rehospitalization for cardiovascular events, and bleeding.ResultsThe addition of low-dose rivaroxaban to DAPT reduced LVT formation within 30 days compared with only DAPT (0.7% vs 8.6%; HR: 0.08; 95% CI: 0.01-0.62; P = 0.015; P < 0.001 for superiority). Net clinical adverse events were lower within 30 days in the rivaroxaban group versus those in the only DAPT group and remained relatively low throughout the follow-up period. There were no significant differences in bleeding events between the 2 groups in 30 days and 180 days. However, 1 case of intracranial hemorrhage (major bleeding) occurred in the rivaroxaban group within 30 days.ConclusionsOur results supported that the short-duration addition of low-dose rivaroxaban to DAPT could prevent LVT formation in patients with anterior STEMI following primary percutaneous coronary intervention. A larger multiple-institution study is necessary to determine the generalizability.     

Antithrombotic Therapy After Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) is a treatment option for symptomatic patients with severe aortic stenosis who are candidates for a bioprosthesis across the entire spectrum of risk. However, TAVR carries a risk for thrombotic and bleeding events, underscoring the importance of defining the optimal adjuvant antithrombotic regimen. Antithrombotic considerations are convoluted by the fact that many patients undergoing TAVR are generally elderly and present with multiple comorbidities, including conditions that may require long-term oral anticoagulation (OAC) (eg, atrial fibrillation) and antiplatelet therapy (eg, coronary artery disease). After TAVR among patients without baseline indications for OAC, recent data suggest dual-antiplatelet therapy to be associated with an increased risk for bleeding events, particularly early postprocedure, compared with single-antiplatelet therapy with aspirin. Concerns surrounding the potential for thrombotic complications have raised the hypothesis of adjunctive use of OAC for patients with no baseline indications for anticoagulation. Although effective in modulating thrombus formation at the valve level, the bleeding hazard has shown to be unacceptably high, and the net benefit of combining antiplatelet and OAC therapy is unproven. For patients with indications for the use of long-term OAC, such as those with atrial fibrillation, the adjunctive use of antiplatelet therapy increases bleeding. Whether direct oral anticoagulant agents achieve better outcomes than vitamin K antagonists remains under investigation. Overall, single-antiplatelet therapy and OAC appear to be reasonable strategies in patients without and with indications for concurrent anticoagulation. The aim of the present review is to appraise the current published research and recommendations surrounding the management of antithrombotic therapy after TAVR, with perspectives on evolving paradigms and ongoing trials.     

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

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Oral Anticoagulation for Patients With Atrial Fibrillation on Long-Term Dialysis

BackgroundPatients on long-term dialysis are at increased risk of bleeding. Although oral anticoagulants (OACs) are recommended for atrial fibrillation (AF) to reduce the risk of stroke, randomized trials have excluded these populations. As such, the net clinical benefit of OACs among patients on dialysis is unknown.ObjectivesThis study aimed to investigate the efficacy and safety of OACs in patients with AF on long-term dialysis.MethodsMEDLINE and EMBASE were searched through June 10, 2019, for studies that investigated the efficacy and safety of different OAC strategies in patients with AF on long-term dialysis. The efficacy outcomes were ischemic stroke and/or systemic thromboembolism, all-cause mortality, and the safety outcome was major bleeding.ResultsThis study identified 16 eligible observational studies (N = 71,877) regarding patients on long-term dialysis who had AF. Only 2 of 16 studies investigated direct OACs. Outcomes for dabigatran and rivaroxaban were limited to major bleeding events. Compared with no anticoagulants, apixaban and warfarin were not associated with a significant decrease in stroke and/or systemic thromboembolism (apixaban 5 mg, hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.30 to 1.17; apixaban 2.5 mg, HR: 1.00; 95% CI: 0.52 to 1.93; warfarin, HR: 0.91; 95% CI: 0.72 to 1.16). Apixaban 5 mg was associated with a significantly lower risk of mortality (vs. warfarin, HR: 0.65; 95% CI: 0.45 to 0.93; vs. apixaban 2.5 mg, HR: 0.62; 95% CI: 0.42 to 0.90; vs. no anticoagulant, HR: 0.61; 95% CI: 0.41 to 0.90). Warfarin was associated with a significantly higher risk of major bleeding than apixaban 5 min/2.5 mg and no anticoagulant (vs. apixaban 5 mg, HR: 1.41; 95% CI: 1.07 to 1.88; vs. apixaban 2.5 mg, HR: 1.40; 95% CI: 1.07 to 1.82; vs. no anticoagulant, HR: 1.31; 95% CI: 1.15 to 1.50). Dabigatran and rivaroxaban were also associated with significantly higher risk of major bleeding than apixaban and no anticoagulant.ConclusionsThis meta-analysis showed that OACs were not associated with a reduced risk of thromboembolism in patients with AF on long-term dialysis. Warfarin, dabigatran, and rivaroxaban were associated with significantly higher bleeding risk compared with apixaban and no anticoagulant. The benefit-to-risk ratio of OACs in patients with AF on long-term dialysis warrants validation in randomized clinical trials.     

Diagnostic yield and technical performance of the novel motorized spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn's disease: a prospective study (with video)

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Rare,Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists

Recurrent abdominal pain is a common reason for repeated visits to outpatient clinics and emergency departments, reflecting a substantial unmet need for timely and accurate diagnosis. A lack of awareness of some of the rarer causes of recurrent abdominal pain may impede diagnosis and delay effective management. This article identifies some of the key rare but diagnosable causes that are frequently missed by gastroenterologists and provides expert recommendations to support recognition, diagnosis, and management with the ultimate aim of improving patient outcomes.     

Development and Validation of a Score for Fibrotic Nonalcoholic Steatohepatitis

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Triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular events in the general population: A systematic review and meta-analysis of cohort studies

AimsThe ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) has been regarded as a novel surrogate indicator of insulin resistance and the atherogenic index of plasma. This meta-analysis aimed to evaluate the association between the TG/HDL-C ratio and the incidence of cardiovascular events in the general population.Data synthesisCohort studies reporting the association between the TG/HDL-C ratio and cardiovascular events in the general population were obtained by a systematic literature search of PubMed, Embase and Web of Science databases until April 11, 2021. 13 cohort studies with a total of 207,515 participants were included in this meta-analysis. In a random-effects model, compared with those with the lowest category of the TG/HDL-C ratio, participants with the highest category were independently associated with a higher risk of cardiovascular events (pooled HR: 1.43, 95%CI: 1.26–1.62, I² = 72.9%). For the presence of publication bias detected by the Egger's test (p = 0.011), correction for publication bias using the trim-and-fill method reduced the HR to 1.26 (95%CI: 1.11–1.44). This result was consistent with the finding of the TG/HDL-C ratio analyzed as a continuous variable (pooled HR per unit increment of the TG/HDL-C ratio: 1.08, 95%CI: 1.04–1.12, I² = 67.0%). Subgroup analyses indicated that population gender, geographical region, duration of follow-up, adjustment for other lipid parameters, adjustment for diabetes and categorical number did not significantly vary the relationship.ConclusionElevated TG/HDL-C ratio may be independently associated with an increased risk of cardiovascular events in the general population. More well-designed studies are needed to confirm the current findings.Registration number in PROSPEROCRD42021244583.     

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Background & AimsPatients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events.MethodsWe performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months).ResultsBased on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P = .02).ConclusionsIn patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality.     

Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Liver Disease

BackgroundAdvanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking.ObjectivesThe aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease.MethodsUsing the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups.ResultsDOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827).ConclusionsIn this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease.     

High-Risk Pulmonary Embolism During Labor: JACC Patient Care Pathways

While in labor, a 37-year-old woman developed acute dyspnea, hypoxemia, and tachycardia. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction, raising the suspicion of acute pulmonary embolism. The patient indeed had bilateral pulmonary embolism, necessitating percutaneous thrombectomy. Her course was complicated by another saddle pulmonary embolus, heparin-induced thrombocytopenia, and COVID-19 infection. This clinical case illustrates the importance of prompt diagnosis of acute pulmonary embolism in a peripartum female patient, the multidisciplinary approach of management, and how to approach clinical complications such as heparin-induced thrombocytopenia. Furthermore, long-term management in acute pulmonary embolism is presented.