Systemic Embolism Research Articles

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.

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 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.

Comparative analysis of vitamin K antagonists and direct oral anticoagulants for left ventricular thrombus management: a retrospective study utilising TriNetX

Abstract Introduction Despite progress in cardiovascular medicine, guidelines for addressing left ventricular thrombus (LVT) remain limited. Furthermore, incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction (MI) adds complexity to treatment decisions. While conventional guidance favors vitamin K antagonists (VKAs), emerging evidence suggests favorable outcomes with direct oral anticoagulants (DOACs). Purpose This study aims to assess the safety and efficacy of DOACs versus VKAs in managing LVT among patients with and without recent acute coronary syndrome (ACS). Methods This was a retrospective observational study conducted within TriNetX, a global federated health research network with access to electronic medical records (EMRs) from participating health care organizations including academic medical centres and community hospitals covering approximately 70 million individuals, mainly in the United States. The search was conducted on 26th Februrary 2024 with a study cohort comprising patients with LV thrombus treated with either DOAC or VKA between 1st December 2013 to 1st December 2023. Subgroup analyses were conducted for patients with ACS within one month and those without ACS within a month of treatment. Cohort data were subject to propensity matching (PSM) for age, gender, ethnicities, medical and drug history. Risk analysis and Kaplan-Meier survival analysis were computed for each subgroup at 90 days since the indexed event. Results Following PSM, a total of 39,770 patients were included and 14,302 were in the ACS group and 24,162 in the non-ACS group. DOAC treatment exhibited favourable outcomes for stroke, bleeding, and systemic embolism (p&amp;lt;0.05) compared to VKA in the overall cohort (Table 1). In the ACS group, DOAC was linked to a reduced risk of stroke and systemic embolism (p&amp;lt;0.05) but not bleeding (p=0.066). In the non-ACS group, DOAC was associated with a decreased risk of stroke and bleeding (p&amp;lt;0.05) but not systemic embolism (p=0.113). Across all groups, there were no disparities in overall all causes of mortalities. Conclusion DOACs demonstrated better safety and efficacy outcomes when compared to VKAs in LVT treatment. Interestingly, DOACs utilisation within the ACS context resulted in a diminished risk of embolic complications without the benefit of reduced bleeding risk seen in patients without ACS, suggesting potential implications of triple therapy within first month of ACS treatment, removing the bleeding risk reduction of DOACs. This shows a fundamental difference in LVT between the 2 groups of patients so future studies should aim to differentiate between the 2.

Atrial fibrillation screening to prevent stroke in persons with low-normal thyrotropin

Abstract Background Screening for atrial fibrillation (AF) has been proposed as a method to prevent strokes in high-risk individuals. Recent trials were unable to prove efficacy for stroke prevention but suggested that a more refined approach may be beneficial. Low-normal thyroid-stimulating hormone (TSH) is a marker for AF and stroke risk and may be used to select individuals for AF screening. Purpose To explore TSH as a tool to select individuals for AF screening to prevent stroke. Methods Post hoc analysis of a clinical trial enrolling 6004 participants with stroke risk factors but no known AF randomized 1:3 to implantable loop recorder (ILR) screening for AF and initiation of oral anticoagulation (OAC) upon AF detection versus usual care (control group). The primary outcome was stroke or systemic embolism (SE). Secondary outcomes included the combination of stroke, SE, or cardiovascular (CV) death, all-cause death, AF diagnosis, and OAC initiation. All outcomes were adjudicated. Results Baseline TSH was measured in 6003 participants (99.98%); 1500 randomized to ILR vs 4503 to control. The mean age was 75±4 years, 2836 (47%) were women. The tertiles of TSH were at ≤1.2, 1.2-1.9, and &amp;gt;1.9 mIU/L. Participants in the first tertile had slightly higher levels of the thyroid hormones (T3, T4, and free T4), were slightly younger, had more smoking pack-years, and higher pulse rate compared to other tertiles. The median follow-up duration was 5.4 (4.9-5.8) years, and no participants were lost to follow-up. AF was diagnosed in 476 (31.7%) participants in the ILR group vs 550 (12.2%) in the control group and this difference was similar across tertiles (p-interaction=0.44). Similar patters were observed for OAC initiation. In the first TSH tertile, participants in the ILR group were significantly less likely to experience the primary outcome (hazard ratio 0.52 [0.30–0.90]; p=0.019) or the combination of stroke, SE, or CV death (hazard ratio 0.54 [0.35–0.84]; p=0.006, respectively) compared to control, while there was no effect in participants with higher TSH (p-interaction 0.029 and 0.014, respectively) and there was no effect on all-cause death in any tertile. When TSH was modelled as a continuous variable, the effect of ILR screening gradually increased with decreasing TSH, with the upper bound of the confidence interval reaching HR&amp;lt;1 at TSH&amp;lt;1.2-1.5 mIU/L. Sensitivity analyses excluding participants with baseline TSH outside reference range (0.3-4.0 mIU/L) and/or treated with thyroid hormone replacement or antithyroid agents yielded similar results. Conclusion In persons with stroke risk factors and TSH &amp;lt;1.2-1.5 mIU/L, ILR screening for AF and anticoagulation upon detection led to significantly decreased stroke risk. There was no effect in persons with higher TSH, though the yield of screening was similar across levels. This suggests that low-normal TSH may indicate benefit from AF screening while higher levels may lead to overdiagnosis.TableFigure

Role of negative transthoracic echocardiography in excluding infective endocarditis

Abstract Background Recent guidelines suggest an extensive role of transesophageal echocardiography (TOE) in the diagnostic work-up for suspected infective endocarditis (IE). However, the negative predictive value of transthoracic echocardiography (TTE) remains poorly investigated. Purpose The purpose of our study was to evaluate the accuracy of TTE in ruling out IE in order to avoid unnecessary TOE, a more invasive and expensive diagnostic exam. Methods We reviewed data of 637 consecutive patients referred to our laboratory of echocardiography with a suspected diagnosis of IE who underwent TOE within 14 days of TTE (median 4.4 days; interquartile range 2.4-7.4). For each patient we obtained age, sex, blood culture results, complete blood count, blood chemistry, evidence of systemic embolism or pulmonary embolism, and presence of moderate/severe heart valve disease, congenital heart disease, valve prostheses and intracardiac devices. Patients with initial doubtful findings at TOE were referred for a follow-up TOE after one week and/or 18F fluorodeoxyglucose positron emission tomography computed tomography to achieve a definitive clinical diagnosis. Patients in whom a clear diagnosis of IE could not be achieved (n=7) were considered to have the disease. Results Of the 637 patients enrolled, 375 had negative TTE for IE (59%). TOE was positive and doubtful for IE in 44 (12%) and 29 (8%) of these patients, respectively. After further assessment, a final diagnosis of IE was achieved in 56 patients (15%). Variables associated with IE at univariable analysis included presence of valve prostheses (p&amp;lt;0.001), systemic or pulmonary embolism (p&amp;lt;0.001), lower platelet count (p=0.003), positive blood culture (p=0.005), aortic valve regurgitation (p=0.02), aortic valve stenosis (p=0.03) and mitral regurgitation (p=0.03). At multivariable logistic regression, independent predictors of IE (OR=odds ratio; CI=confidence interval) included evidence of systemic or pulmonary embolism (OR 17.75, 95% CI 6.66-47.3, p&amp;lt;0.001), bioprosthetic heart valves (OR 2.93, 95% CI 1.31-6.53 p=0.023) and lower platelet count (OR 0.995, 95% CI 0.991-0.998, p=0.003). Among the subgroup of patients (n=183, 49%) with no evidence of embolism, no bioprosthetic valve and platelet count &amp;gt;190,000/mL (median value), IE was diagnosed in 11 patients only (6%). Conclusions In our study, a negative TTE in the subgroup of patients with suspected IE showing platelet count &amp;gt;190,000/mL and absence of embolism and valvular bio-prosthesis, had a negative predictive value for IE of 94%, suggesting that, in this subset of patients, TOE can initially be delayed and performed only if clinical suspicion continues to remain high.

The efficacy and safety of NOAC in very elderly atrial fibrillation patients; data from the Korean national health insurance cohort registry

Abstract Background Data regarding efficacy and safety on anticoagulation in very elderly atrial fibrillation patients are relatively sparse. Purpose We investigated the clinical benefit of anticoagulation with NOAC in very elderly AF patients through national healthcare insurance registry. Methods Clinical data of 862,935 patients who were diagnosed with AF from 2015 to 2020 were collected for analysis. Patients under the age of 85, prior history of ICH, GI bleeding and prior prescription days of aspirin, warfarin and NOAC exceeding 90 along with follow up period less than 90 days were excluded. Results A total of 10,625 patients were eligible for analysis. Patients with OAC (HR: 0.60, 95% CI 0.53-0.69), p&amp;lt;0.001) showed higher efficacy regarding systemic embolism compared to aspirin (HR: 0.84, 95% CI 0.74-0.95, p=0.008) and no treatment group. Individual comparison of NOAC and aspirin via propensity score matching showed that patients with NOAC (HR: 0.71, 95% CI 0.61-0.85), p&amp;lt;0.001) showed higher event free survival regarding systemic embolism compared to aspirin. Bleeding risk was also higher for NOAC (HR: 1.28, 95% CI 1.07-1.56, p=0.006) group but did not result in commensurate increase in mortality (HR:0.60, 95% CI 0.45-0.81, p&amp;lt;0.001). Conclusions Anticoagulation with NOAC in very elderly patient showed higher event free survival regarding systemic embolism. Despite having higher event rate of bleeding, eventual death did not show any association with NOAC.

Dynamic recommendation for anticoagulant treatment in patients with atrial fibrillation using deep reinforcement learning method

Abstract Background Recent evidence suggests that the guideline-directed anticoagulant therapy for atrial fibrillation (AF) remains controversial. Widely-used CHA2DS2-VASc score is solely based on limited traditional cardiovascular risk factors, omitting AF characteristics and other markers of thromboembolic risk. A more efficient, safer and more personalized anticoagulant approach is warranted. Purpose To develop a data-driven deep reinforcement learning (DRL) model for guiding dynamic anticoagulant treatment in AF patients to improve cardiovascular outcomes. Methods Participants of this study were enrolled from the multicentred China Atrial Fibrillation (China-AF) Registry between August 2011 and December 2022, who were with regular follow-up every 6 months. We excluded patients on warfarin at baseline due to its declining usage trend in non-valvular AF patients in China. The DRL model was trained in 70% randomly selected patients for optimal dynamic decision-making, and then subsequently tested in the remaining 30%. Data of sociodemographic characteristics, AF characteristics, medical history, lifestyle factors, laboratory examination, and medications were input for model training. Concordance rate between DRL model’s recommendations and physicians’ actual decisions of non-vitamin-K-antagonist oral anticoagulant (NOAC) prescription among all visits before censoring was calculated for each patient. Primary outcome was the composite of cardiovascular death, ischemic stroke, transient ischemic attack or systemic embolism (SSE), and major bleeding. Shapley additive explanation analysis ranked the most important factors affecting decision-making of the DRL model. Results A total of 20068 patients (mean age: 63.0±12.0 years; 36.2% female) were randomly divided into a training cohort of 14050 patients and a testing cohort of 6018 patients. The model’s NOAC recommendations were mostly affected by age, prior NOAC prescription, body mass index, hypertension history and prior statin prescription (Figure 1). Patients with concordance rates of 50.1%-75% and 75.1%-100% had significant risk reductions for the primary outcome (adjusted HR =0.63; 95% CI, 0.46-0.85; P = 0.003 and adjusted HR =0.59; 95% CI, 0.46-0.75; P &amp;lt;0.001, respectively), compared to those with a concordance rate of 0-25%. Similar results were observed for all-cause death, cardiovascular death and SSE outcomes, that patients with the highest concordance rate had a significant lower risk, compared to those with the lowest concordance rate. There was a nonsignificant but similar trend with regard to major bleeding events (Figure 2). Conclusions This modelling study suggests that a data-driven DRL model might provide more efficient, safer and more personalized anticoagulant suggestions, potentially assisting physicians in clinical practice.

Impact of the complexity of percutaneous coronary intervention on clinical outcomes in patients with atrial fibrillation: a real-world study

Abstract Background Atrial fibrillation (AF) always coexisted with percutaneous coronary intervention (PCI), and complex PCI has increased in recent years. However, limited data exist on clinical outcomes in patients with AF and underwent complex PCI. Purposes We aimed to explore the prognosis of patients with AF who had underwent PCI. Methods This was a prospective, observational study which enrolled 1132 participants consecutively. Complex PCI was defined as PCI performed to ≥ 3 separate major coronary vessels; ≥3 stents implanted; ≥3 lesions treated; or total stented &amp;gt; length 60 mm. The primary endpoint was defined as major adverse cardiovascular event (MACE) including all-cause death, spontaneous myocardial infarction (MI), stroke, systemic embolism or ischemia-driven revascularization. Major bleeding events were defined according to Thrombolysis in Myocardial Infarction (TIMI) criteria. Results A total of 1132 patients who underwent PCI with AF were enrolled. The mean age was 66.6 ±8.9, and 75.1% were male. 320 participants (28.2%) were undergoing complex PCI. During a median follow-up of 1045 days, the primary outcome occurred in 52 of 320 patients (16.2%) in the complex PCI group and 105 of 812 patients (12.9%) in the non-complex PCI group (adjusted hazard ratio: 1.31; 95% confidence interval: 1.08-1.58; P = 0.007), driven by higher rate of MI ( aHR=2.17, 95%CI, 1.00-4.70 and ischemic driven revascularization (aHR=1.86, 95%CI, 1.01-3.45). TIMI major bleeding events were more commonly observed in complex PCI group (aHR=1.15, 95%CI, 1.01-1.31). Conclusion The complexity of PCI was an independent risk factor of adverse clinical outcomes, especially in MI, revascularization and TIMI major bleeding events in patients with AF.K-M curves of eventsK-M curves of events

Direct Oral Anticoagulants versus Vitamin K Antagonists for the management of left ventricular thrombus after myocardial infarction: A meta-analysis

Abstract Background/Introduction Left ventricular (LV) thrombus formation is not an uncommon complication after acute myocardial infarction (AMI) in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario remains poorly-defined. Purpose The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with Vitamin K antagonists (VKAs) for the management of LV thrombus following AMI. Methods A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after MI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and random-effects meta-analyses were conducted to synthesize pooled ORs. Results Eight studies comprising a total of 605 patients were included (Table). DOACs were associated with an almost 2-fold higher likelihood for achieving thrombus resolution compared to VKAs (pooled OR 1.95 [1.25-3.04]; p =0.003, I2 =0 %), while they achieved a 70% lower risk for systemic embolism (pooled OR 0.30 [0.12-0.75]; p =0.01, I2 =0%). The use of DOACs was associated with a 54% lower risk for bleeding compared to VKAs (pooled OR 0.46 [0.26-0.84]; p =0.01, I2 =0 %). Overall, patients receiving DOACs had a 63% lower risk to reach the composite outcome of any bleeding, systemic embolism, cardiovascular hospitalization, or all-cause death, compared with patients using VKAs (pooled OR 0.37 [0.23-0.60]; p &amp;lt;0.0001, I2 =0%) (Figure). Conclusion DOACs appear to have a more favorable efficacy and safety profile compared to VKAs for the management of LV thrombus following AMI.Graphical abstractTable

Stratification of residual thromboembolic risk among anticoagulated atrial fibrillation patients: a hierarchical cluster analysis from a global, real-world population

Abstract Background Assessment of residual thromboembolic risk among atrial fibrillation (AF) patients despite being on oral anticoagulants (OACs) poses a significant challenge. This study utilises a hierarchical cluster analysis approach to identify risk phenotypic profiles in a global prospective AF registry. Methods Data were drawn from recently diagnosed non-valvular AF patients receiving OACs, as recorded in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. A hierarchical cluster analysis based on patient demographics was performed to identify distinct phenotypes. The incidence and risks of thromboembolic events (ischaemic stroke, transient ischaemic attack, or systemic embolism) and relevant events (major bleeding and all-cause death) were compared across clusters. Results The study included 22,410 patients (mean age 70±8 years; 56% male), from which 5 phenotypes were delineated: Cluster 1 ("uncontrolled hypertension"), Cluster 2 ("young with a history of coronary artery disease"), Cluster 3 ("young and obese"), Cluster 4 ("frailty"), and Cluster 5 ("non-paroxysmal AF with tachycardia"). Cluster 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years), major bleeding (1.92/100 person-years), and all-cause mortality (6.02/100 person-years). Conversely, Cluster 3 showed the lowest risk profiles across all outcomes (thromboembolic events: 0.64 events/100 person-years, major bleeding: 0.83 events/100 person-years, and all-cause death: 1.44 events/100 person-years). Cluster 1 displayed a moderate thromboembolic event rate (1.04/100 person-years), although lower rates were observed in Clusters 2 and 5 (Figure 1). Conclusions Hierarchical cluster analysis effectively identified distinct phenotypes within a global AF population, offering valuable insights for stratifying the risks of residual thromboembolic events and other significant outcomes in anticoagulated AF patients (Figure 2).Figure 1Figure 2

Association of R2-CHA2DS2-VASc score and clinical outcomes after bioprosthetic valve replacement: Subanalysis from BPV-AF registry

Abstract Background Although bioprosthetic valve (BPV) replacements are becoming more common, there are limited studies about prognostic prediction method for patients after BPV replacement. R2-CHA2DS2-VASc score is modified CHA2DS2-VASc score by adding reduced estimated glomerular filtration rate (eGFR &amp;lt; 60 mL/min/1.73m2). It is increasingly used for the prediction of cardiovascular (CV) events in patients with atrial fibrillation (AF), device implantation, and acute coronary syndrome. Purpose We aimed to evaluate the predictive value of R2-CHA2DS2-VASc score for future CV events in patients after BPV replacement. Methods BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients that underwent BPV replacement. Patients were stratified into three risk groups according to their R2-CHA2DS2-VASc score as follows; low (scores, 0–1), moderate (scores, 2–4), and high (scores, 5–11). The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure hospitalization, and cardiac death. Results A total of 766 patients were included in the analysis. The mean age was 80.3 years and 419 patients (54.7%) were female. Mean R2-CHA2DS2-VASc score was 4.1±1.5. Low, moderate, and high R2-CHA2DS2-VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. Median follow up period was 491 (interquartile range: 393-561) days. Kaplan-Meier analysis showed higher incidence of the composite CV events in high R2-CHA2DS2-VASc score group (Log rank test; p&amp;lt;0.01). Multivariate Cox proportional hazards regression analysis revealed that the R2CHA2DS2-VASc score as a continuous variable was an independent predictor of CV events (hazard ratio 1.33, 95% confidence interval 1.18 to 1.51, p&amp;lt;0.01). Conclusion The R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.Cumulative Incidence for Composite CV Ev

Embolic myocardial infarction. Clinical characteristics, etiology, and prognosis

Abstract Introduction A small proportion of acute myocardial infarctions (AMI) are of embolic origin. There is limited information about the actual causes of these AMIs, the population they affect, and their prognosis. Purpose The purpose of this study is to describe the clinical characteristics of embolic myocardial infarction (EMB-AMI) and compare them with atherosclerotic myocardial infarction (ATH-AMI). Methods Retrospective observational study of patients admitted for AMI at our centre (2010-2022). Clinical characteristics, ethology, and prognosis are described, and the EMB-AMI cohort is compared with the ATH-AMI cohort. Results Out of 6046 AMIs, 75 (1.2%) were EMB-AMI. Cardiovascular risk factors were similarly distributed in both groups, except for a higher rate of smokers, males, and older age in the ATH-AMI group (figure 1). Additionally, EMB-AMIs more frequently presented as ST-elevation myocardial infarctions. Hospital mortality for EMB-AMI and ATH-AMI was 10.7% vs. 6.2% (p=0.177), and the rate of mechanical complications was higher in the EMB-AMI group (6.7% vs. 1.8%, p=0.009). Of the EMB-AMIs, 8 (10.7%) had other systemic emboli during admission, including a 5.3% of strokes (vs. 1.4% in the ATH-AMI group, p=0.021). In EMB-AMIs, coronary embolism was multivessel in 8 (10.7%) patients, 46 (61.3%) had distal vessel involvement, and 66 (88.0%) had initial TIMI 0 flow. Thrombectomy was performed in 51 (68%) patients, with 82% of them being successful. However, final TIMI was 0-1 in 36 (48%) patients and 3 in 32 (42.7%) patients. Angioplasty was performed in 12 (16.0%) patients. In 52 (67.5%) EMB-AMI patients, atrial fibrillation (AF) was diagnosed at some point during follow-up, and in 43 (57.3%), embolism was exclusively attributed to AF. Nine (12.0%) embolisms were attributed to prosthetic thrombosis, although thrombosis was confirmed by imaging in only one third of cases. Six (8%) embolisms were attributed to endocarditis, and 5 (6.7%) to patent foramen ovale. Rest of embolism causes detected are outlined in figure 2. During a mean follow-up of 44.8 months, 11 patients experienced new embolic events in the EMB-AMI cohort: 7 strokes, 2 probable coronary embolisms, and 2 systemic embolisms. Twenty-seven (36.0%) patients died during follow-up (38.4% of whom from cardiac causes), and 18 (24.0%) were admitted for heart failure. Conclusions EMB-AMI exhibits specific clinical characteristics distinct from ATH-AMI, with varied etiologies, with atrial fibrillation being the most common cause. These AMIs are associated with a higher incidence of complications, including mechanical complications of myocardial infarction and recurrence of embolic events.Characteristics and outcomesEmbolic source

Risk and causes of hospital admission in patients with atrial fibrillation on treatment with oral anticoagulants

Abstract Background Atrial fibrillation (AF) is associated with an increased risk of hospitalisation, although the main reasons for hospital admission and the role of antiarrhythmic drugs are not clarified. Objective The aim of our study was to assess the incidence rate and the factors associated with all-cause, cardiovascular and AF-related causes of hospitalisation in patients suffering from AF. Methods This is a prospective single-centre ongoing study (ATHERO-AF cohort) which included 2782 patients affected by non-valvular AF on oral anticoagulants. The primary endpoints were all-cause, cardiovascular and AF-related hospitalisation. Cardiac hospitalizations were defined as (non-AF) arrhythmias, acute coronary syndromes, heart failure (HF), systemic embolism, hypertensive urgency, vascular/cardiac surgery. The AF-related hospitalisation was defined as a recurrence of AF in paroxysmal pattern or as a high-rate symptomatic AF episode in persistent/permanent patterns. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to risk of hospitalisation. Results Overall, 43.5% of patients were women with a mean age of 74.6±9.1year. Patients were followed for a mean of 31±26.8 months. We registered 1205 (12.1%/year) hospitalisations for any reason, 533 (5.7%/year) for cardiovascular causes and 180 (2.0%/year) were AF-related hospitalisations (Central illustration). Among the anti-arrhythmic drug use, we highlighted that flecainide and propafenone were associated with AF-related hospitalisations in paroxysmal and in persistent/permanent patterns (HR 1.861, 95%CI 1.116-3.101 and HR 1.947, 95%CI 1.069-3.548, respectively). Amiodarone (HR 3.012, 95%CI 1.835-4.943) and verapamil or diltiazem (HR 2.067, 95%CI 1.117-3.825) were associated with an increased risk of AF-related hospitalisations in persistent/permanent AF pattern. Furthermore, cancer was associated (HR 1.802, 95%CI 1.057-3.070) with increased risk of hospitalisation due to AF-related causes. Conversely, beta-blockers and digoxin were not associated with increased risk of hospital admission. Conclusions Hospitalisations of patients with AF are frequent for both cardiovascular and non-cardiovascular causes. Among the AF-related ones, the use of antiarrhythmic drugs emerged as associated with increased risk of hospitalisations, hypothesizing their poor effect in preventing AF episodes. For these reasons, we suggest carefully considering their use, reserving them for symptomatic patients with frequent AF recurrences.Central Illustration

Medication adherence and antithrombotic therapy outcomes: insights from a post-hoc analysis of the AFIRE trial

Abstract Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial established noninferiority in efficacy and superiority in safety endpoints of rivaroxaban monotherapy over rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, the impact of medication adherence to rivaroxaban on AFIRE study outcomes remains unclear. Purpose This post-hoc analysis aimed to explore the influence of medication adherence on AFIRE trial results. Methods Among 2,120 patients, participants were classified into adherent and non-adherent groups based on self-reported measures, which were further verified through on-site visits to the facilities. Adherent patients were defined as those who reported consistently taking their medication as prescribed. The primary efficacy endpoint comprised stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or all-cause death, including cerebral events. Analysis also examined differences in the primary efficacy endpoint between adherent and non-adherent patients. Results Of the 2,120 patients, 2,012 (94.9%) were adherent to rivaroxaban, while 108 (5.1%) were non-adherent. Among adherent patients, rivaroxaban monotherapy showed significantly better efficacy outcomes compared to combination therapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.54–0.98; p=0.04, Figure 1A). However, primary efficacy outcomes did not significantly differ among non-adherent patients (HR 0.64, 95% CI 0.23–1.81, p=0.40, Figure 1B). Adherent patients exhibited improved outcomes relative to non-adherent patients, though this difference was not statistically significant (HR 1.68; 95% CI 0.99–2.85; p=0.05, Figure 2A). In clinically high-risk patients with a history of angina pectoris, those who demonstrated adherence to medication (n=1281) exhibited significantly better efficacy outcomes compared to non-adherent patients (n=68) (HR 1.97; 95% CI 1.09–3.56; p=0.03, Figure 2B). Conclusions Rivaroxaban monotherapy versus combination therapy showed favorable efficacy outcomes in patients with good adherence, consistent with the overall AFIRE trial. However, these benefits were not observed in non-adherent patients. Adherence to rivaroxaban is crucial for achieving its maximum therapeutic effect as monotherapy.Figure1Figure2