Systemic Embolism Research Articles

Cardiovascular comorbidities and their prognostic value in small cell lung cancer patients with chemoradiotherapy.

Small cell lung cancer (SCLC) is an extremely malignant subtype of lung cancer because of its high potential for metastases. Cardiac invasion of SCLC is a serious concern that may lead to systemic embolism or tract obstruction. It has aroused much concern that cardiovascular comorbidities may significantly affect the survival of SCLC patients and their treatment decisions. We consecutively recruited 772 small cell lung cancer (SCLC) patients between January 2011 and December 2018 from 4 cancer specialty hospitals in China. Only newly diagnosed primary cancer inpatients were included. Univariable and multivariable adjusted Cox proportional hazard models were conducted to evaluate the risk factors associated with mortality. Hazard ratios (HRs) for mortality and corresponding 95% confidence intervals (95% CIs) were calculated. The prevalence of cardiovascular diseases (CVDs) was 34.6% in all SCLC patients. Log-rank analysis presented statistically significant differences in median survival time (MST) between patients with CVD and without CVD in all SCLC patients (9.0months vs. 15.0months, P = 0.005) and patients with chemotherapy only (12.0months vs. 18.0months, P = 0.048). Pericardial effusion (HR 1.671, 95% CI 1.082-2.580, P = 0.021) and heart failure (HR 1.752, 95% CI 1.290-2.379, P < 0.001) were independent risk factors associated with mortality in all SCLC patients. VTE is related to poorer prognosis in patients with chemotherapy only (HR 5.558, 95% CI 1.335-23.135, P = 0.018) and chemoradiotherapy (HR 3.057, 95% CI 1.270-7.539, P = 0.013). Comprehensive management of CVD comorbidities is of vital importance for the long-term prognosis of SCLC patients.

Selection of Non-vitamin K Antagonist Oral Anticoagulant for Stroke Prevention in Atrial Fibrillation Based on Patient Profile: Perspectives from Vietnamese Experts. Part 1.

In Asia, especially Vietnam, AF is a common arrhythmia and is linked to a higher risk of stroke and systemic embolism. Anticoagulation therapy for stroke prevention in AF patients can result in bleeding complications. To effectively manage AF, adopting appropriate anticoagulation and addressing modifiable risk factors are crucial. Vietnamese clinicians are particularly interested in non-vitamin K antagonist oral anticoagulants (NOACs), a recent development in AF treatment. However, the lack of head-to-head trials comparing NOACs makes selecting a specific NOAC challenging. This review aims to provide a comprehensive overview of the available clinical evidence on NOACs for stroke prevention in AF to assist clinicians in making informed decisions and improving treatment outcomes in patients with AF. The first part of this review will present the current landscape of AF in Vietnam, focusing on AF prevalence and highlighting gaps in clinical practice. Furthermore, this part extensively discusses the anticoagulation strategy for both primary and secondary stroke prevention in AF.

Safety of the injectable expanding biopolymer foam for non-compressible truncal bleeding in swine

BackgroundA novel hydrophobically modified chitosan (hm-chitosan) polymer has been previously shown to improve survival in a non-compressible intra-abdominal bleeding model in swine. We performed a 28-day survival study to evaluate the safety of the hm-chitosan polymer in swine. MethodsFemale Yorkshire swine (40–50 kg) were used. A mild, non-compressible, closed-cavity bleeding model was created with splenic transection. The hm-chitosan polymer was applied intra-abdominally through an umbilical nozzle in the same composition and dose previously shown to improve survival. Animals were monitored intraoperatively and followed 28 days postoperatively for survival, signs of pain, and end-organ function. Gross pathological and microscopic evaluations were performed at the conclusion of the experiment. ResultsA total of 10 animals were included (hm-chitosan = 8; control = 2). The 2 control animals survived through 28 days, and 7 of the 8 animals from the hm-chitosan group survived without any adverse events. One animal from the hm-chitosan group required early termination of the study for signs of pain, and superficial colonic ulcers were found on autopsy. Laboratory tests showed no signs of end-organ dysfunction after exposure to hm-chitosan after 28 days. On gross pathological examination, small (<0.5 cm) peritoneal nodules were noticed in the hm-chitosan group, which were consistent with giant-cell foreign body reaction in microscopy, presumably related to polymer remnants. Microscopically, no signs of systemic polymer embolization or thrombosis were noticed. ConclusionProlonged intraperitoneal exposure to the hm-chitosan polymer was tolerated without any adverse event in the majority of animals. In the single animal that required early termination, the material did not appear to be associated with end-organ dysfunction in swine. Superficial colonic ulcers that would require surgical repair were identified in 1 out of 8 animals exposed to hm-chitosan.

Anticoagulant Prescribing Patterns in New-Onset Atrial Fibrillation After Cardiac Surgery

BackgroundPostoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with an increased risk of thromboembolic stroke. Recommendations regarding the optimal anticoagulant, timing of initiation, and duration of therapy remain uncertain. MethodsAdministrative databases were used to include adult patients who presented with POAF after cardiac surgery between January 1, 2015, and December 31, 2020. Key exclusion criteria included preexisting atrial fibrillation, mechanical valve replacement, or anticoagulant prescription fill within 6 months before the index admission. ResultsA total of 3214 of patients were included, and 878 (27.3%) were prescribed an oral anticoagulant (OAC) on discharge, with 536 (61%) prescribed warfarin and 342 (39%) prescribed a direct OAC. More than half of the patients (56.1%) stopped their OAC by 6 months. There was no difference in stroke or systemic embolism at 30 days, 3 months, or 6 months between those with and without anticoagulation prescribed. However, those on any OAC had higher rates of any bleeding at all time points. ConclusionsA minority of patients who presented with POAF after cardiac surgery were prescribed OAC, with warfarin being the most common agent. OAC initiation was associated with increased bleeding risk, warranting special consideration when assessing a patient’s risk of stroke with the increased risk of bleeding, particularly in the postoperative period.

Comparing safety and efficacy: MemoLefort versus watchman for left atrial appendage closure

BackgroundThe MemoLefort is a new plug occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF). This study compares the safety and efficacy of MemoLefort and the well-established Watchman occluder for LAAC. MethodsBetween January 2021 and September 2022, a cohort of 189 consecutive patients who underwent LAAC with MemoLefort or Watchman at The Second Affiliated Hospital of Wenzhou Medical University were included. Patients with MemoLefort or Watchman devices were compared in terms of the primary safety endpoints encompassing major periprocedural complications and major bleeding events at follow-up, the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, and the combined hazard endpoint, a composite of all the above-mentioned hazards. ResultsOf the MemoLefort group (n = 83) and Watchman group (n = 106), the mean age, CHA2DS2-VASc score, and HAS-BLED score were 67.6 ± 9.2 vs. 69.0 ± 10.6 years, 3.9 ± 1.9 vs. 3.8 ± 1.9, and 1.6 ± 1.0 vs. 1.7 ± 1.2, respectively. After a median follow-up duration of 198 (99–329) vs. 334 (171–497) days, the primary endpoints of efficacy [2/49, 4.1% (MemoLefort) vs. 2/97, 2.1% (Watchman); hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.20–11.08; P = 0.68] and safety (1/49, 2.0% vs. 5/97, 5.2%; HR, 0.26; 95% CI, 0.05–1.31; P = 0.19), as well as the combined hazard endpoint (3/49, 61% vs. 6/97, 6.2%; HR, 0.70; 95% CI, 0.18–2.58; P = 0.59) were similar between groups. ConclusionsIn the short term, LAAC with MemoLefort provided similar efficacy, safety, and net clinical benefit in comparison to Watchman devices.

Country and health expenditure are major predictors of withholding anticoagulation in atrial fibrillation patients at high risk of stroke

BackgroundGuidelines for patients with atrial fibrillation (AF) at high thromboembolic risk recommend oral anticoagulants (OACs) for preventing stroke and systemic embolism (SE). The reasons for guideline non-adherence are still unclear.AimThe...

Nodule pulmonaire suspect chez un grand tabagique : faut-il faire une biopsie ?

Sclerotherapy is a widely used as a lifesaving therapeutic option in cases of upper gastrointestinal bleeding (UGB) due to ruptured gastro-esophageal varices (GOV) in cirrhotic patients, especially when there exists a portosystemic shunt. This endoscopic technique can entail many complications, including systemic and non-thrombotic pulmonary embolism (PE). While multiple pulmonary parenchymal manifestations have been described following sclerotherapy of GOV, to our knowledge no solitary suspicious pulmonary nodule has been described. We report the case of 55-year-old man with heavy smoking history who was referred to our pulmonary clinic for work-up of a solitary pulmonary nodule. He was known to have liver cirrhosis with history of massive UGB due to rupture of GOV two months before. He was treated with sclerotherapy by injecting a 3 cc of Histoacryl/lipiodole solution. The post- endoscopic phase was unremarkable. An enhanced CT scan of chest and abdomen performed two months later showed a right upper lobe nodule, even though at that point, the patient was completely asymptomatic. This was ascribed to non-thrombotic PE secondary to sclerotherapy due to complete resolution of the nodule on a CT scan carried out at 2-month follow-up. At that point, his condition did not require any further treatment. Solitary pulmonary nodule is one of the radiologic manifestations of PE subsequent to sclerotherapy of GOV. Awareness and radiologic follow-up of this unusual radiologic presentation may prevent unnecessary biopsies.

First-in-human study of the CAPTIS embolic protection system during transcatheter aortic valve replacement.

Stroke and other clinically significant embolic complications are well documented in the early period following transcatheter aortic valve replacement (TAVR). The CAPTIS device is an embolic protection system, designed to provide neurovascular and systemic protection by deflecting debris away from the brain's circulation, capturing the debris and thus avoiding systemic embolisation. We aimed to study the safety and feasibility study of the CAPTIS complete cerebral and full-body embolic protection system during TAVR. A first-in-human study investigated the safety, feasibility and debris capturing ability of CAPTIS during TAVR. Patients were followed for 30 days. The primary endpoints were device safety and cerebrovascular events at 72 hours. Twenty patients underwent TAVR using balloon-expandable or self-expanding valve systems. CAPTIS was successfully delivered, positioned, deployed, and retrieved in all cases, and TAVR was successfully completed without device-related complications. No cerebrovascular events were observed. High numbers of debris particles were captured in all patients. The use of the CAPTIS full-body embolic protection system during TAVR was safe, and it captured a substantial number of debris particles. No patient suffered from a cerebrovascular event. A randomised clinical trial is warranted to prove its efficacy.

Anticoagulant-Related Nephropathy in a Patient on Coumadin

Abstract Introduction/Objective Anticoagulant therapy is commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation. However, it carries the risk of bleeding and can lead to serious complications such as anticoagulant-related nephropathy (ARN), a recently described entity characterized by hematuria and acute kidney injury. This report presents a case of a 79-year-old male with a history a patient with a history of atrial fibrillation on coumadin, highlighting the importance of monitoring for anticoagulant-related complications and the need for prompt diagnosis and management to prevent further renal damage. Methods/Case Report The kidney biopsy showed evidence of underlying hypertensive and diabetic nephropathy, with nodular and global glomerulosclerosis, moderate to marked interstitial fibrosis, and tubular atrophy along with many red cell casts of variable ages in the tubules indicative of anticoagulant-related nephropathy. Additionally, one glomerulus had a partial cellular crescent associated with a focus of blood clot, likely related to heavy hematuria. Patient is seronegative for ANCA. The immunofluorescence microscopy is non-contributory due to absence of glomerulus in the sample. Electron microscopy showed diffuse foot process effacement and microvillous transformation of podocytes, increased mesangial matrix, and thickened glomerular basement membranes, but no immune complex deposits. these ultrastructural features confirm the background diabetic nephropathy. Results (if a Case Study enter NA) NA Conclusion Anticoagulant-related nephropathy (ARN) is a rare but serious complication of anticoagulation therapy that can result in hematuria and acute kidney injury. Our case highlights the importance of monitoring for anticoagulant-related complications, especially in high-risk patients with multiple comorbidities. Prompt diagnosis and management of ARN is essential to prevent further renal damage. In this case, despite initial improvement with vitamin K therapy, the patient developed severe renal dysfunction requiring dialysis and renal biopsy. This emphasizes the need for increased awareness and early recognition of ARN in patients on anticoagulant therapy.

Effectiveness and safety of oral anticoagulant therapy in a real-world cohort with atrial fibrillation: The SIESTA-A study protocol.

Oral anticoagulants (OACs) are first-line drugs for stroke prevention in patients with atrial fibrillation (AF). The introduction of new lines of therapy with direct oral anticoagulants (DOACs) has led to a decreased use of vitamin K antagonists (VKAs). Comparative analyses of DOACs in clinical trials are scarce and the comparator has mostly been warfarin. Their impact on health outcomes in observational studies has not always been consistent. The aim of this study is to evaluate the effectiveness and safety of DOACs and VKAs in patients with AF using Real-World Data (RWD). Population-based retrospective cohort study using RWD from actual practice. Period: January 2012-December 2020. Inclusion criteria: patients with AF who had not taken OACs in the previous 12 months. Exclusion criteria: <40 years, with severe mitral stenosis, or valvular heart disease or aortic and/or mitral valve procedures. Data source: The Andalusian Population Health Database, Spain. Outcome measures: a) Effectiveness: ischaemic stroke, transient ischaemic attack, systemic and pulmonary embolism, and death; b) Safety: gastrointestinal and intracranial haemorrhaging; Independent variables: age, sex, comorbidities, medication and health resource use, CHA2DS2-VASC, HAS-BLED, and analytical tests. Statistical analysis: crude incidence analysis, survival models, Kaplan-Meier, Cox regression analysis adjusted for possible confounding and paired analysis by propensity score matching.

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.

Association between aortic thrombi detected using non-obstructive general angioscopy and atrial fibrillation.

Atrial fibrillation (AF) is an independent risk factor for stroke and systemic embolism. Cardiogenic and aortogenic emboli are causes of stroke or systemic embolism. Non-obstructive general angioscopy (NOGA) can be used to diagnose aortic intimal findings, including thrombi and atherosclerotic plaques, but little is known about NOGA-derived aortic intimal findings in patients with AF. This study focused on aortic intimal findings in patients with AF and evaluated the association between AF and aortic thrombi detected using NOGA. We enrolled 283 consecutive patients with coronary artery disease who underwent NOGA of the aorta between January 2017 and August 2022. Aortic intimal findings were screened using NOGA after coronary arteriography. The patients were divided into two groups according to their AF history (AF, n = 50 and non-AF, n = 233). Patients in the AF group were older than those in the non-AF group. Sex, body mass index, and coronary risk factors were not significantly different between the two groups. In the NOGA findings, the presence of intense yellow plaques and ruptured plaques was not significantly different between the two groups. Aortic thrombi were more frequent in the AF group than in the non-AF group (92.0 vs. 71.6%, p < 0.001). Multivariate logistic regression found that AF was independently associated with aortic thrombi (odds ratio 3.87 [95% CI 1.28-11.6], p = 0.016). The presence of aortic thrombi observed using NOGA was associated with AF in patients with coronary artery disease. The roles of aortic thrombi as well as cardiogenic embolism may require clarification.

Multimodality Quantification of Thrombus Deposition in Extracorporeal Membrane Oxygenation (ECMO); Correlating Oxygenator Computed Tomography Imaging, Electron Microscopy and Histology to Clinical Outcomes

Introduction: Extracorporeal membrane oxygenation (ECMO) is essential for supporting cardiopulmonary function in critically ill patients, However, ECMO incurs thrombogenic risks due to activation of coagulation factors and blood cells by the biomaterial surfaces. This leads to complications such as frequent device replacement and systemic embolization despite the use of anticoagulation, suggesting additional mechanisms contribute to medical device-associated thrombosis. We propose that the geometry of the ECMO oxygenator significantly influences the structure and extent of clot formation and stability. To investigate this, we employed quantitative imaging and histologic techniques for a high-resolution, three-dimensional analysis of clot morphology in ECMO components, aiming to enhance our understanding of clot formation mechanisms, correlate these observations to clinical outcomes, and develop effective mitigation strategies. Methods: We developed a prospective study in which patients consented to the collection of blood samples, used ECMO components, and collection of relevant clinical variables. Computed tomography (CT) images were acquired using an Inveon microCT. H&amp;E stains, scanning electron microscopy (SEM), and CT images were processed through the Dragonfly software to accomplish a 3D visualization and analysis of clot composition. Clinical demographics and ECMO characteristics were recorded for each patient. Results: Digital photographs of used oxygenators are displayed in figure (A). Through CT scans, we quantified clot formation of distinct densities across the layers of the ECMO oxygenator (D). The results were able to quantify intraoxygenator thrombosis with high fidelity (27.65%, 14.56%, and 26.35% of the available membrane area was thrombosed across three representative oxygenators). Using a frontal CT scan to investigate clot formation identified five layers of varying structures across the intended path of blood flow (B). Clot formation was observed in layer 4 and layer 5, in which thrombosis occluded up to 12.2% of the layer on average. The overall ranking of clot formation under hemodynamic performance changes for all five layers was as follows: layer 5 &amp;gt; layer 4 &amp;gt; layer 1 = layer 2 &amp;gt;&amp;gt; layer 3. The use of anticoagulation at the time of ECMO decannulation significantly reduced the content of clot formation (P&amp;lt;0.0001). We then correlated digital biomarkers from imaging with thrombus composition. Detailed histological examination (HE) and SEM was undertaken on dismantled oxygenators (B &amp; C). We focused on thrombi at the interfaces and within the hollow fibers of the oxygenator. SEM and HE staining illustrated increased thickness, length, and density of fibrin structures in the thrombi from layer 5 to layer 4, whereas the numbers of platelets and cells decreased. Overall, layer 5 exhibited the most diverse types of thrombi, including blood cell-rich, platelet-rich, and fibrin-rich clots. We also observed aligned clots and significant clot formation in the hollow fiber area of layer 4, reflecting the geometry of the specific layer. Discussion: This pilot study examined the potential for imaging-based modalities to evaluate device associated thrombosis ex vivo, correlating these imaging findings to direct observations of thrombus composition and location. This methodology provides a platform to investigate ECMO device failure, identifying the key locations within select oxygenators where local device modification may be of most benefit. Future research will prioritize designing membrane oxygenator properties to minimize thrombus deposition, and will allow us to incorporate the use of serial imaging endpoints in future clinical trials evaluating medical device-associated thrombosis.

An extension of biorelevant fed-state dissolution tests to clinical pharmacokinetics – A study on gastrointestinal factors influencing rivaroxaban exposure and efficacy in atrial fibrillation patients

A direct oral anticoagulant rivaroxaban fails to prevent stroke and systemic embolism in one-to-several percent of patients with nonvalvular atrial fibrillation (NVAF), but the reasons are unknown. The study used semi-mechanistic in vitro-in vivo prediction (IVIVP) modeling to explore the reasons for ineffective thrombosis prevention in NVAF patients. Steady-state drug concentrations in plasma were measured at 0 h (Ctrough), 3 h (C3h), and 12 h post-dosing in thirty-four patients treated with 20 mg rivaroxaban daily. The clinical data were compared against “virtual twins” generated with a novel IVIVP model that combined drug dissolution modeling, mechanistic description of gastric drug transit, and population pharmacokinetics defining the variability of drug disposition. The nonresponders had significantly lower C3h and Ctrough than the responders (p < 0.001) and the covariates included in the population pharmacokinetic submodel did not fully explain this difference. Simulations involving varied gastrointestinal parameters in the “virtual twins” revealed that lower small intestinal effective permeability (Peff), rather than a slower stomach emptying rate, could explain low rivaroxaban exposure in the nonresponders. IVIVP modeling was effectively used for exploring pharmacotherapy failure. Low Peff, found as a major determinant of ineffective rivaroxaban treatment, encourages further research to find (pato)physiological factors influencing suboptimal absorption.

COVID-19–Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease

BackgroundAltered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. ObjectivesThe purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. MethodsCOVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. ResultsOf 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. ConclusionsACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24 h.

Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Safety and healthcare resource utilisation in patients undergoing left-atrial appendage closure - A nationwide analysis

Abstract Background Percutaneous left-atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited. Purpose To analyse outcomes of peri-procedural in-hospital safety and healthcare resource utilisation after percutaneous LAAC. Methods The US National Inpatient Sample was utilised to identify AF patients undergoing LAAC from 2016 to 2019. Primary outcomes (safety) were in-hospital stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolisation and mortality. Secondary outcomes (resource utilisation) were adverse discharge disposition, hospital length of stay (LOS) and treatment costs. Logistic and Poisson regression models were used to analye outcomes by adjusting for 10 confounders. Results 11,240 adult patients (with 41.9% being female) with AF undergoing LAAC were included. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0-0.24] (P=0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality remained stable (0.14%). Hospital LOS decreased by 18% (0.78-0.87, P&amp;lt;0.001) and adverse discharge rate by 41% (95% CI 0.41-0.86, P=0.005) between 2016 and 2019, while hospital costs did not significantly change (P=0.2). Of note, female patients had a higher risk of PE (OR 2.86 [95% CI 2.41-6.39]) and SE (OR 5.0 [95% CI 1.28-43.6]), while patients with multiple comorbidities had higher risks of major bleeding (P&amp;lt;0.001), mortality (P=0.031), longer hospital LOS (P&amp;lt;0.001) and increased treatment costs (P=0.073). Male patients had the most peculiar decrease in adverse discharge rate between 2016 and 2019: OR 0.45 [95% CI 0.27-0.77]. Significant differences in all outcomes were observed between male and female patients across US regions (Figure). Subgroup analyses confirmed that female patients had a prolonged LOS and higher risk of adverse discharge disposition than male patients. Conclusions LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.

Current concepts of treatment for left ventricular thrombus: A sys-tematic meta-analysis comparing direct oral anticoagulants versus vitamin K-antagonists

Abstract Background/Introduction Left ventricular thrombus (LVT) is a dreaded complication after myocardial infarction (MI) and is traditionally treated with Vitamin K antagonists (VKAs) for 3-6 months. Despite a gap of evidence, the broad use of direct oral anticoagulants (DOACs) for other thromboembolic disorders has triggered an increasing off-label use for DOACs in LVTs and has stimulated for expanding research focusing on DOAC´s utility for patients with LVT. Purpose To assess the safety and efficacy of DOACs versus VKAs for the treatment of LVT with a systematic meta-analysis. Methods We conducted a systematic search according to the PRISMA guidelines to identify all existing studies comparing DOACs and VKAs for the treatment of LVT. Forest plots and pooled odds ratios have been calculated for major bleeding events, strokes and systemic embolism, and for thrombus resolution. Results We have included a total of 13 studies with a pooled sample size of 2243 patients. 601 patients (26.8%) were treated with DOACs and 1642 patients (73.2%) with VKAs. The mean age was 55 and 59 years in the DOACs and VKAs group and sex was equally distributed with a male predominance of 81% in both groups. As underlying heart disease, most patients suffered from acute or chronic ischemic cardiomyopathy and presented with a mean left ventricular ejection fraction (LVEF) of 32% at admission. Baseline characteristics of patients included in each primary study are summarized in table 1. The pooled odds ratio of stroke or systemic embolism in patients treated with DOACs versus VKAs was 0.84 (95% CI 0.59-1.19) (p= 0.32). Compared to VKAs, we suggest that the use of DOACs may be associated with a reduced risk for major bleeding incidents without reaching statistical significance (OR 0.63 (95% CI 0.39-1.04) (p = 0.07). LVT resolution was similar and independent of the antithrombotic regimen (OR 0.91 (95% CI 0.7-1.19), p=0.50). Conclusions Based on our meta-analysis we conclude that DOACs seem to be non-inferior to VKAs for the treatment of LVT in terms of thrombus resolution, stroke and systemic embolism, and bleeding incidents. Despite these promising findings, several important aspects such as the duration of anticoagulation, and the type and dosing of the DOAC agent are still poorly understood. To close the lack of evidence for DOACs in LVTs, an adequately powered, randomized trial is needed.

Left atrial strain and risk of systemic embolic event in rheumatic mitral stenosis with sinus rhythm

Abstract Backgrounds Stroke and systemic embolism might be an important complication of rheumatic mitral stenosis (MS) even though patients are in sinus rhythm (SR), but the risk of embolic events in this population are not well studied. Purpose We aimed to evaluate the risk factors of embolic events in patients with rheumatic MS and SR. Methods From the multi-center retrospective registry of 2426 patients with rheumatic MS, we included patients with rheumatic MS and SR (n=583) between January 2000 and December 2021. After exclusion of patients who had history of systemic embolic events, taking the anticoagulants, combined significant aortic valve dysfunction, and a history of valve surgery. We finally analyzed 443 patients. The primary outcome was defined as composite of stroke, transient ischemic attack, noncentral nervous system embolism. Results Among 448 patients (77.1% female; mean age, 52.3 ± 10.1 years), systemic embolic events developed in 38 (8.4 %) patients with annual incidence rate of 4.6/100 person-year during mean follow-up period of 96.4 ± 61.1 months (median 94.2 months). Patients who had systemic embolic events were significantly older and had higher the prevalence of hypertension and diabetes than those who did not, without significant differences in left atrial (LA) dimensions, volumes, pulmonary artery systolic pressure. Instead, LA strain was significantly impaired in patients with systemic embolic events (19.1 ± 9.3 vs. 15.5 ± 8.07, p= 0.034). In the multivariate analysis, LA strain was independent predictors of systemic embolic events [HR 0.96, 95 % CI: 0.93-0.99; P = 0.021], after adjustment for confounding factors. The impaired LA strain (LA reservoir strain &amp;lt; 16.6 %) also had incremental prognostic value for development of systemic embolic events over clinical factors and traditional echocardiographic parameters (Figure). Conclusions Impaired LA strain is a predictor of stroke and systemic embolism in patients with rheumatic MS in SR. Considering the risk for embolism, oral anticoagulation might be considered in patients with rheumatic MS in SR and impaired LA strain.Figure

Risk of thromboembolic and bleeding events in patients with atrial fibrillation after valvular intervention in either aortic or mitral position

Abstract Background The optimal oral anticoagulant treatment (OAC) for patients with atrial fibrillation (AF) undergoing valvular intervention is uncertain. Mitral valve prostheses are believed to be more thrombogenic than the aortic due to lower flow velocity across the valves. The only randomized controlled trial of AF patients with biological valve prostheses included only patients receiving mitral valve prostheses (1). It is unclear if these findings could be extrapolated to patients receiving aortic valve prostheses. Purpose To describe baseline characteristics and comorbidities of patients receiving biological valve prostheses in aortic or mitral valve position and to investigate possible associations between valve position and the incidence of cardiovascular (CV) death, ischemic stroke or systemic embolism and major bleeding. Methods All patients in Sweden undergoing open heart surgery with aortic or mitral valve replacement with biological prostheses between 2010-2016 with known AF were included. The study cohort was identified in the SWEDEHEART registry. Information on comorbidities, drug exposure and occurrence of outcome events was collected from SWEDEHEART and other national registries. Association between the position of valve prosthesis (mitral and aortic) and incidence of outcome events was investigated using Cox regression analysis. Multivariable adjustments were made for comorbidities. Results In total, 2359 patients with AF underwent aortic (n=2103) or mitral (n=256) valve replacement. The median age was 75 and 73 years, respectively. Hypertension, diabetes mellitus and previous TIA were more common in the aortic valve group, whereas heart failure and previous major bleeding was more frequently observed in the mitral group. In both groups, about 50% of the patients were not on OAC treatment at time of discharge from valve intervention, despite that the mean CHA2DS-VASc score was 3.3 and 3.2, respectively. Mitral valve prostheses were associated with similar risk of CV death (hazard ratio (HR) 1.09; 95% confidence interval (CI), 0.77 – 1.56), ischemic stroke and systemic embolism (HR 1.27; 95% CI, 0.85-1.92) compared to aortic valve prostheses. In contrast, receiving mitral valve prosthesis was associated with lower risk of major bleeding compared to aortic prosthesis (HR 0.58; 95% CI 0.38 – 0.88). Conclusion(s) The study indicated similar risk of CV death, ischemic stroke and systemic embolism among patients with AF undergoing valve replacement with biological prostheses in either aortic or mitral position. Mitral valve replacement was associated with lower risk of major bleeding.