Systemic Embolism Research Articles

Systemic air embolism associated with endoscopic retrograde cholangiopancreatography: A case report

BACKGROUND Endoscopic retrograde cholangiopancreatography (ERCP) is a key procedure for diagnosing and treating biliary and pancreatic disorders. Although effective, it carries risks, including rare but severe complications such as air embolism. CASE SUMMARY We report a case of a 58-year-old man who developed extensive air embolism during ERCP. He previously underwent a Whipple procedure and experienced a sudden drop in vital signs and loss of consciousness. Immediate intervention with hyperbaric oxygen therapy and supportive care led to gradual recovery. Imaging confirmed widespread air embolism, which resolved with continued treatment. CONCLUSION Air embolism is a rare, critical complication of ERCP, especially in patients with prior surgery such as pancreaticoduodenectomy. Early detection and prompt treatment, including hyperbaric oxygen therapy, are crucial for favorable outcomes.

Blue toe syndrome - systemic cholesterol crystal embolism secondary to cardiovascular procedures: a forensic autopsy report of two cases.

Blue toe syndrome, also referred to as cholesterol crystal embolism is characterized by the distal embolization of cholesterol crystals originating from ruptured atherosclerotic plaques. This condition commonly arises in the context of cardiovascular procedures. Emboli from the thoracoabdominal aorta primarily affect the downstream extremities and intra-abdominal viscera, often resulting in fatal atheroembolic renal failure. Owing to its insidious and delayed onset, antemortem diagnosis of cholesterol crystal embolism is often underrecognized. Two cases of blue toe syndrome secondary to cardiovascular procedures are presented. In Case 1, the patient died 35 days after coronary angioplasty, whereas in Case 2, the patient developed toe necrosis 95 days after endovascular aortic repair, leading to progressive renal failure over the following five years. A comprehensive forensic autopsy included external examination, skin biopsy, histopathological examination of major organs, and serum biochemical evaluation of renal function parameters. Two cases of blue toe syndrome secondary to cardiovascular procedures are presented. In Case 1, the patient died 35 days after coronary angioplasty, whereas in Case 2, the patient developed toe necrosis 95 days after endovascular aortic repair, leading to progressive renal failure over the following five years. A comprehensive forensic autopsy included external examination, skin biopsy, histopathological examination of major organs, and serum biochemical evaluation of renal function parameters. This report underscores the importance of including systemic cholesterol crystal embolism in the differential diagnosis of blue toe syndrome, particularly in patients with a history of cardiovascular procedures. Fingertips serve as reliable indicators of impaired blood perfusion. To assess blue toe syndrome accurately, we highlight the value of focusing on the toe tips where cholesterol crystal embolism can be consistently detected.

Long-term risks and benefits of oral anticoagulation in atrial fibrillation patients with cancer: A report from the GLORIA-AF registry.

Anticoagulation therapy in patients with atrial fibrillation (AF) and concomitant cancer can be challenging due to the significantly increased risk of both embolism and bleeding. Moreover, the benefits and risks of vitamin K antagonists (VKA, eg. warfarin) versus non-vitamin K antagonist oral anticoagulants (NOACs) in such patients are less well understood. From the prospective, global, multi-centered Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), we characterized these patients according to their history of prior cancer when enrolled. All patients received anticoagulant therapy. The primary outcome was the composite of all-cause mortality, stroke, transient ischemic attack, systemic embolism. The secondary endpoints were all-cause mortality, cardiovascular death, stroke, major bleeding and thromboembolism during the 3 years follow-up period. Cox regression analyses were used to calculate the hazard ratio (HR) and confidence interval (CI) following propensity score matching (PSM). Overall, among 16,700 patients enrolled in Phase III in GLORIA-AF, 1725 (10%) patients had concomitant cancer(s) at enrolment. After PSM, the primary outcome occurred in 250 (14.8%) of patients with cancer(s) and 160 (9.3%) without cancer(s) (HR, 1.62 [95% CI, 1.33-1.97], p < .001) during the 3 years follow-up period. The risk of all-cause mortality was significantly higher in patients with cancer(s) versus non- cancer(s) (HR, 1.71 [95% CI, 1.37-2.12], p < .001). In patients with cancer(s), after PSM, the use of NOACs was associated with reduced risk of the primary outcome compared with that of VKA (HR, .69 [95% CI, .49-.99], p = .043), as well as a lower risk of thromboembolism (HR, .49 [95% CI, .24-1.00], p = .051), but the risk of major bleeding was not significantly different (HR, .87 [95% CI, .48-1.56], p = .635). Subgroup analysis in patients with cancers showed a reduced risk of major bleeding with NOACs compared with VKA (HR, .18 [95% CI, .04-.8], p = .024) in patients with coronary artery disease (CAD). For the main cancer subtypes (genitourinary, breast, gastrointestinal, haematological and skin), the trends for the risk of primary outcome were consistently favouring NOACs compared with VKA without any significant interaction among these five cancers. Cancer is a common comorbidity in patients with AF and is associated with increased risk of composite of all-cause mortality and thromboembolism. Compared with VKA, NOACs was associated with a lower risk of composite events and showed an advantage in lower risk of thromboembolism, as well as a reduced risk of major bleeding when CAD was also present.

Abstract 4125076: Catheter Ablation Alone Versus Catheter Ablation With Combined Percutaneous Left Atrial Appendage Closure For Atrial Fibrillation: A Systematic Review and Meta-analysis

Background: Combined catheter ablation (CA) with left atrial appendage closure (LAAC) may produce comprehensive treatment for atrial fibrillation (AF) whereby rhythm control is achieved and stroke risk is reduced without the need for chronic oral anticoagulation. However, the efficacy and safety of this strategy is still controversial. Aim: To investigate the efficacy and safety of a combined CA with LAAC approach to treat AF in patients moderate-to-high-risk for bleeding. Methods: This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Risk of bias was assessed using the Modified Newcastle-Ottawa scale and Cochrane risk of bias tool. Eligible studies reported outcomes in patients with AF who underwent combined CA and LAAC versus CA alone. Studies performing CA without pulmonary vein isolation were excluded. Results: Eight studies comprising 1878 patients were included (2 RCT, 6 observational). Pooled results showed no difference in arrhythmia recurrence (risk ratio [RR] 1.05; 95% confidence interval [CI] 0.84-1.30), stroke or systemic embolism (RR 0.71; 95% CI 0.26-1.94), total procedure time (mean difference 31.45 minutes; 95% CI -5.91-68.81), or major periprocedural complications (RR 1.28; 95% CI 0.28-5.89) when comparing combined CA and LAAC versus CA alone. Conclusion: Combined CA with LAAC for AF is associated with similar rates of arrhythmia free survival, stroke, major periprocedural complications, and procedure time when compared to CA alone. A combined strategy may be as safe and efficacious for patients moderate-to-high-risk for bleeding events to negate the need for chronic oral anticoagulation.

Abstract 4138813: The Use of Direct Oral Anticoagulants for Valvular Atrial Fibrillation in Central Australia

Background: In developed countries, valvular atrial fibrillation (vAF) in the setting of rheumatic heart disease (RHD) disproportionately impacts minority groups. In Australia, Indigenous Australians account for 92% of cases despite only representing 3.8% of the population. Studies to date, such as the INVICTUS trial, support the use of Vitamin K antagonists (VKAs) over direct oral anticoagulants (DOACs) in vAF. However, this assumes consistent adherence and regular clinic follow up. Reduced access to monitoring and dispensing clinics in Central Australia remains a challenge in the provision of VKAs and the use of DOACs may address this. Hypothesis: DOACs may be comparably effective with VKAs in preventing major adverse cardiac and cerebrovascular events (MACCE) in a real-world vAF population. Aim: To conduct a real-world retrospective observational study examining rates of MACCE for patients on VKAs or DOACs for vAF in Central Australia over a five-year period. Methods: The Northern Territory RHD Register was accessed to identify patients with RHD and vAF in January 2019. Demographic and five-year outcome data (until January 2024) were collected. The primary outcome was MACCE, a composite of ischaemic stroke, systemic embolism, non-fatal myocardial infarction, cardiovascular death and all-cause mortality. The primary safety endpoint was major bleeding. Statistical analyses were conducted as both intention-to-treat (ITT) based on initial anticoagulation and as-treated (AT) based on anticoagulation prior to MACCE or trial endpoint, each excluding patients without anticoagulation. Results: 61 patients were included. The mean age was 61.9 ± 13.9 years and 68.9% were female. At baseline, 65.6% received VKA, 14.8% DOAC and 19.7% were not anticoagulated. 30.6% of patients crossed over from the ITT analysis, with a non-significant trend favouring switch to DOAC (11 vs 0, p=0.09). In the ITT analysis (n=49), there was no significant difference in MACCE (25.0% vs 22.2%, p=0.86) or major bleeding (20.0% vs 11.1%, p=0.53) between VKA and DOAC groups. In the AT analysis (n=51), there was no significant difference in MACCE (27.3% vs 16.7%, p=0.39) or major bleeding (18.2% vs 22.2%, p=0.73) between VKA and DOAC groups. Conclusion: Over a five-year period, there was a trend towards use of DOACs over VKAs in vAF. This study demonstrates that DOACs may be as effective as VKAs for reducing MACCE in a real-world vAF population however further investigation is required.

Preoperative management and anticoagulant efficacy in atrial myxoma-associated acute ischemic stroke: a case report and literature review

Acute ischemic stroke (AIS) is a common complication of atrial myxoma (AM), and most emboli originate from a thrombus attached to the surface of the myxoma, with occasional shedding of tumor fragments leading to stroke. Clinical manifestations of AM include mitral valve obstruction, systemic embolism, and weakness. However, neurological deficits and other nonspecific manifestations may mask the presence of AM. The surgical resection is the most effective treatment for these conditions. However, the main problem is the lack of consensus regarding the prevention and treatment of stroke complicated by myxoma during the perioperative period. This study aims to improve the diagnosis and treatment of AM and the associated AIS. Here, we report the case of a 27-year-old patient with AM who presented with chest pain, palpitations, and sudden dizziness and had a stroke under anticoagulant treatment during the admission period. We also reviewed and summarized the clinical presentations and characteristics of similar previously reported cases. Our review emphasized the importance of early diagnosis and appropriate perioperative management of AM and its associated AIS.

Refining the CHA2DS2VASc risk stratification scheme: Shall we drop the Sex Category criterion?

The CHA2DS2VASc score is recommended for stroke risk stratification in patients with atrial fibrillation (AF). This score assigns one extra point to female sex based on evidence from the early 2000s suggesting higher thromboembolic risk in women. This incremental risk of thromboembolism in women has decreased over time between 2007 and 2018, becoming non-significant in recent years. To assess the impact of removing the sex category (Sc) from the CHA2DS2VASc score, thus validating a non-sex CHA2DS2VASc (i.e., CHA2DS2VA) score. We analysed UK primary and secondary care data comprising 195,719 patients with AF followed between 1998-2016 (mean age: 75.9±12.3 years; 49.2% women). Among 126,428 non-anticoagulated patients, we compared the CHA2DS2VASc vs. CHA2DS2VA scores every calendar year. Throughout 413,007 patient-years, a total of 8,742 events of ischaemic stroke or systemic embolism were recorded. Sex differences in thromboembolic risk were not observed in the lower-risk population, but higher stroke rates were consistently seen in female patients in the higher-risk category (i.e., CHA2DS2VA ≥2). C-statistics for both CHA2DS2VA and CHA2DS2VASc scores were similar over the years (ranging from 0.62 to 0.71). With CHA2DS2VA no relevant differences were observed in IDI, and NRI resulted in improved reclassification (11%) in lower thromboembolic risk groups. NRI suggested misclassification in higher thromboembolic risk patients (-7%), but this did not affect their indication for anticoagulation (i.e., patients retained their high-risk status). Removing Sc from the CHA2DS2VASc score does not affect its ability to discriminate thromboembolic events in the AF population. Use of CHA2DS2VA may simplify initial decision-making for thromboprophylaxis.

Efficacy of direct oral anticoagulants vs. warfarin in left ventricular thrombus in myocardial infarction: systematic review and meta-analysis.

Current recommendations for antithrombotic strategies in left ventricular (LV) thrombus following myocardial infarction (MI) remain uncertain. This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in LV thrombus following MI. A systematic search using four databases, including PubMed, Embase, Web of Science, and Cochrane CENTRAL, was conducted from inception to 8 July 2024, without language restrictions. The inclusion criteria were studies that included patients with LV thrombus following MI and compared the efficacy or safety of DOACs and warfarin. There were 11 studies (3 randomized and 8 nonrandomized) included in this meta-analysis, involving 14 927 participants. We used a random-effects model for this meta-analysis. DOACs were associated with higher thrombus resolution than warfarin, with a risk ratio (RR) of 1.07 [95% confidence interval (CI) 1.00-1.15], P = 0.04. Similarly, DOACs were associated with a lower rate of stroke and systemic embolism, with an RR of 0.84 (95% CI 0.78-0.90), P < 0.01. DOACs also marginally reduced the rate of major bleeding compared with warfarin, with an RR of 0.87 (95% CI 0.75-1.00), P = 0.05. DOACs were associated with higher rates of LV thrombus resolution, lower rates of stroke/systemic embolism, and marginally reduced major and bleeding events compared with warfarin in patients with LV thrombus following acute MI. Therefore, DOACs may be a reasonable alternative to warfarin in this setting.

Autologous Serum Tear Production in Anticoagulated Patients.

Autologous serum tears (ASTs) are produced from serum obtained by blood draw and used to treat severe dry eye diseases. Multiple cases of failed AST production occurred due to serum becoming a solidified, gel-like substance after centrifugation. The aim of this study was to identify risk factors associated with inability to compound AST. From January 2019 to December 2022, 99 patients received AST produced at Mayo Clinic in Arizona. Patient demographics, medical diagnoses, medications, laboratory results, and events surrounding blood draws were obtained through an IRB-approved retrospective chart review. The laboratory and pharmacy protocol procedures were observed in person after the occurrence of the last production issue. Ten total clotted serum episodes occurred in 4 patients, each with multiple occurrences. The indication for AST was chronic ocular graft-vs-host disease (n = 3) and Sjögren syndrome (n = 1). Eighty percent of episodes were associated with either a systemic infection (n = 7) or pulmonary embolism (n = 1) within the prior month. At the time of blood draw, all 4 patients were treated with antiplatelet and/or anticoagulation medications, including rivaroxaban, apixaban, aspirin, and low-molecular-weight heparin. The AST protocol was increased from 30 to 60 minutes of resting time to allow clotting before centrifugation. Inadequate clotting during this stasis period likely resulted in fibrinogen remaining suspended in the serum, leading to solidified plasma instead of liquid serum. We hypothesize risk of inadequate clotting would be increased in patients taking anticoagulation or antiplatelet medications. Our recommendations include ensuring 60-minute collection tube resting time for all patients, including those on anticoagulation medication.

Recurrent Systemic Embolization From Bicuspid Aortic Valve Endocarditis in the Setting of Anti-coagulation Use

Recurrent Systemic Embolization From Bicuspid Aortic Valve Endocarditis in the Setting of Anti-coagulation Use

New left ventricular thrombus and embolic events in left ventricular dysfunction postmyocardial infarction

Background: We aimed to assess the incidence and evolution of new left ventricular thrombus (LVT), and the incidence of manifest systemic embolism, in patients with severe left ventricular (LV) systolic dysfunction postacute anterior myocardial infarction (MI) who had been discharged on dual antiplatelet therapy. Methods: We prospectively included consecutive patients with postacute anterior MI and LV ejection fraction (LVEF) ≤35% or apical aneurysms or large infarctions with LVEF ≤40%. Transthoracic echocardiography (TTE) confirmed no LVT before hospital discharge, and a second TTE was performed at 30 days and a third one at 3 months. All TTE studies were prespecified to assess LVT, and the patients were screened for the development of clinically manifest systemic embolisms. Results: Two hundred and two consecutive patients (males 93%; mean age 55.2±6.4 years; mean LVEF 29.5±5.0%) were included. At 30 days (interquartile range: 2837 days), a new LVT was detected in 12 (5.9%) patients. Oral anticoagulant was added to all patients with LVT, and aspirin was continued in 5 (42.7%) patients for a month. The 3month TTE showed favorable evolution of LV size, LVEF and apical wall motion score index compared to the baseline. At 3 months, the LVT disappeared in 7 (58.3%) patients and 5 patients still had a mural LVT of smaller size, and none got new LVT. Among the group without LVT, one patient had a stroke, and another had a myocardial infarction and died. Conclusions: In contemporary practice, and using routine TTE, the incidence of new LVT in patients with severe LV dysfunction postacute anterior MI is low. They have a favorable LVT evolution with minor risk for clinically manifest systemic embolism.

In subclinical AF, the benefit of apixaban vs. aspirin on stroke or systemic embolism trended higher with CHA2DS2-VASc >4.

Lopes RD, Granger CB, Wojdyla DM, et al. Apixaban vs aspirin according to CHA2DS2-VASc score in subclinical atrial fibrillation: insights from ARTESiA. J Am Coll Cardiol. 2024;84:354-364. 39019530.

Comparison of Direct Oral Anticoagulants and Vitamin K Antagonists for Left Ventricular Thrombus: A Global Retrospective Study

IntroductionGuidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOAC) versus vitamin K antagonist (VKA) in managing left ventricular thrombus among patients with and without recent myocardial infarction. MethodsThis retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013, to December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days since the indexed event. ResultsA total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs. 13.7%, RR=0.859, 95% CI 0.816-0.905, p<0.001), major bleeding (4.8% vs. 5.3%, RR=0.902, 95% CI 0.829-0.982, p=0.018), and systemic embolism (3.5% vs. 4.2%, RR=0.841, 95% CI 0.762-0.928, p=0.001) compared to VKAs in overall cohort. Within acute coronary syndrome group (N=14,302), DOACs had lower stroke (12.3% vs. 14.4%, RR=0.860, 95% CI 0.791-0.935, p<0.0001) and systemic embolism (3.1% vs. 4%, RR=0.774, 95% CI 0.651-0.919, p=0.003) risks. For non-acute coronary syndrome group (N=24,162), DOACs had lower stroke (11.4% vs. 13.1%, RR=0.868, 95% CI 0.811-0.929, p<0.001) and major bleeding (4.8% vs. 5.5%, RR=0.877, 95% CI 0.787-0.977, p=0.017) risks. No significant differences in all-cause mortality were observed across groups. ConclusionDOACs demonstrated better safety and efficacy outcomes when compared to VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome.

Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Liver Cirrhosis.

Comparing direct oral anticoagulants (DOACs) and warfarin's efficacy and safety in patients with nonvalvular atrial fibrillation (AF) and liver cirrhosis (LC). Evidence of the pharmacodynamics of DOACs is limited in patients with AF and LC. A retrospective cohort study was conducted in the largest hospital system in Taiwan, involving patients with AF and LC for the years 2012 to 2021. Hazards of thromboembolic events (ischemic stroke, transient ischemic attack, and systemic embolism), intracranial hemorrhage, gastrointestinal, major bleeding, and all-cause mortality were investigated with a new-user, active comparator design. Inverse probability of treatment weighting was applied to balance potential confounders between treatment groups. In total, 478 DOAC users and 247 warfarin users were included. DOACs and warfarin demonstrated similar trends in preventing thromboembolic events, namely ischemic stroke [adjusted hazard ratio (aHR), 1.05 (95% CI: 0.42-2.61)], transient ischemic attack [aHR, 1.36 (95% CI: 0.18-10.31)], and systemic embolism [aHR, 0.49 (95% CI: 0.14-1.70)]. DOAC use was associated with a similar risk of intracranial hemorrhage [aHR, 0.65 (95% CI: 0.26-1.59)] and gastrointestinal bleeding [aHR, 0.64 (95% CI: 0.39-1.03)], a decreased risk of major bleeding [aHR, 0.64 (95% CI: 0.42-0.99)], and a reduction in mortality [aHR, 0.73 (95% CI: 0.54-0.99)]. DOAC users exhibited a significant reduction in major bleeding risk in patients with Child-Pugh class A (aHR, 0.48; 95% CI: 0.33-0.70). DOACs showed potential safety advantages over warfarin for patients with nonvalvular AF and LC, particularly in reducing major bleeding risk in those with Child-Pugh class A.

The impact of OCEANIC-AF and the future of factor XIa inhibitors

The OCEANIC-AF trial was terminated early due to inferiority of asundexian compared with apixaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation.1 However, the promisingly low bleeding rates support continued exploration of factor XIa inhibitors. Future efforts should focus on achieving greater factor XIa inhibition and identifying patient populations that may benefit most from these therapies.

The ETNA-AF Europe registry: 4-year data of edoxaban use in atrial fibrillation in the Italian real world compared to the European cohort

The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years. Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population. In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding. These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): a multicentre, blinded-endpoint, phase 4, randomised controlled trial

The optimal timing of anticoagulation for patients with acute ischaemic stoke with atrial fibrillation is uncertain. We investigated the efficacy and safety of early compared with delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischaemic stroke associated with atrial fibrillation. We performed a multicentre, open-label, blinded-endpoint, parallel-group, phase 4, randomised controlled trial at 100 UK hospitals. Adults with atrial fibrillation and a clinical diagnosis of acute ischaemic stroke and whose physician was uncertain of the optimal timing for DOAC initiation were eligible for inclusion in the study. We randomly assigned participants (1:1) to early (ie, ≤4 days from stroke symptom onset) or delayed (ie, 7-14 days) anticoagulation initiation with any DOAC, using an independent online randomisation service with random permuted blocks and varying block length, stratified by stroke severity at randomisation. Participants and treating clinicians were not masked to treatment assignment, but all outcomes were adjudicated by a masked independent external adjudication committee using all available clinical records, brain imaging reports, and source images. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days in a modified intention-to-treat population. We used a gatekeeper approach by sequentially testing for a non-inferiority margin of 2 percentage points, followed by testing for superiority. OPTIMAS is registered with ISRCTN (ISRCTN17896007) and ClinicalTrials.gov (NCT03759938), and the trial is ongoing. Between July 5, 2019, and Jan 31, 2024, 3648 patients were randomly assigned to early or delayed DOAC initiation. 27 participants did not fulfil the eligibility criteria or withdrew consent to include their data, leaving 3621 patients (1814 in the early group and 1807 in the delayed group; 1981 men and 1640 women) in the modified intention-to-treat analysis. The primary outcome occurred in 59 (3·3%) of 1814 participants in the early DOAC initiation group compared with 59 (3·3%) of 1807 participants in the delayed DOAC initiation group (adjusted risk difference [RD] 0·000, 95% CI -0·011 to 0·012). The upper limit of the 95% CI for the adjusted RD was less than the non-inferiority margin of 2 percentage points (pnon-inferiority=0·0003). Superiority was not identified (psuperiority=0·96). Symptomatic intracranial haemorrhage occurred in 11 (0·6%) participants allocated to the early DOAC initiation group compared with 12 (0·7%) participants allocated to the delayed DOAC initiation group (adjusted RD 0·001, -0·004 to 0·006; p=0·78). Early DOAC initiation within 4 days after ischaemic stroke associated with atrial fibrillation was non-inferior to delayed initiation for the composite outcome of ischaemic stroke, intracranial haemorrhage, unclassifiable stroke, or systemic embolism at 90 days. Our findings do not support the current common and guideline-supported practice of delaying DOAC initiation after ischaemic stroke with atrial fibrillation. British Heart Foundation.

From the INVICTUS Trial to Current Considerations: It’s Not Time to Retire Vitamin K Inhibitors Yet!

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

MITRAL STENOSIS PRESENTATION REVEALING ALARGE LEFT ATRIAL MYXOMA

Introduction: Cardiac myxoma (CM) is the most frequent benign primary cardiac tumor. Around 75% of myxomas originate in the left atrium 20% arise from the right atrium while the remaining 5% are born from both the atria and the ventricle. Atrial myxomas can result in many symptoms: heart failure, systemic or pulmonary embolism, arrhythmias, and conductive disorders, or also constitutional symptoms (such as fever, and weight loss). It largely relies on the tumors size, location, and architecture. It can obstruct the blood flow, mimicking mitral stenosis. The surgical management is the cornerstone of this entity. Case Report: A 63-year-old female with a past medical history of diabetes and arterial hypertension was admitted to our department for palpitations and acute heart failure symptoms.The physical examination revealed an irregular pulse with a tachycardia of 150 bpm. The blood pressure was at 118/80 mmHg. It also revealed lower limb edema, lung crackles, and ascites with a mitral stenosis murmur. EKG showed atrial fibrillation at 150HR . Transthoracic echocardiography found dilated atriums with a large mass in the left atrium causing mitral pseudo stenosis . Discussion: Myxomas are primary cardiac tumors that originate from multipotent mesenchymal cells. They can occur at any age but mostly between 30 and 60 years. The incidence of myxoma in women is 2 to 4 times higher than in men. Clinically, atrial myxomas vary from asymptomatic especially with small tumor size, to non-specific symptoms (dyspnea, lower limb and pulmonary oedema, angina, syncope, and palpitation) and constitutional symptoms such as fever, fatigue, and weight loss. The diagnosis of atrial myxoma based on its presentation is challenging. echocardiography is usually the modality of choice which helps identify the location of the mass whether itÂ’s intra or pericardial, its size, attachment and mobility. Furthermore, it differentiates atrial myxoma from any thrombus or vegetation. Once a presumptive diagnosis of myxoma has been made on imaging studies, prompt resection is required because of the risk of embolization or cardiovascular complications, including sudden death. Conclusion: Myxoma continues to be a significant challenge for emergency physicians due to its non-specific symptoms and overlap with other conditions. The discrepancy between mild symptoms and the serious consequences the condition carries, necessitates high index of suspicion and thorough investigation to timely diagnose it among a long list of differentials.

Atrial fibrillation and multimorbidity: How to choose the perfect direct oral anticoagulant?

Atrial fibrillation is one of the most common tachyarrhythmias, the prevalence of which is steadily increasing due to an increase in the proportion of the elderly population. The presence of a comorbidities in elderly patients with atrial fibrillation, increasing the risk of thromboembolic events, has a significant impact on the clinical strategy of atrial fibrillation, as well as on the choice of therapeutic tactics, especially anticoagulant therapy with proven efficacy and low risk of bleeding. One of the most common concomitant diseases in patients with atrial fibrillation are chronic kidney disease, anemia and coronary artery disease. These comorbidities in patients with atrial fibrillation not only increase the risk of stroke and/or systemic embolism, but are also accompanied by an increased risk of cardiovascular mortality, all causes mortality, and hemorrhagic events. At the same time, according to research data, about half of polymorbid patients with atrial fibrillation do not receive anticoagulant therapy, which indicates a low awareness of physicians about rational pharmacotherapy based on clinical recommendations for this cohort of patients. The drug of choice with the most studied safety profile and a high degree of efficacy in these patients is apixaban from the group of direct oral anticoagulants. Unlike vitamin K antagonists and other representatives of direct oral anticoagulants, apixaban, according to the conducted studies, is associated with a more significant reduction in the risk of thromboembolic events, and most importantly, has a lesser effect on the risks of bleeding in patients, predisposing to hemorrhagic complications, with atrial fibrillationand concomitant coronary artery disease, anemia, chronic kidney disease.