Peri-device leak (PDL) following left atrial appendage closure (LAAC) can be diagnosed by both transesophageal echocardiography (TEE) and cardiac computed tomography (CCT). Yet, there is a substantial discrepancy in leak quantification. We propose a novel ABC classification of LAA sealing for TEE and CCT based on the pattern of intra-device thrombosis (IDT). A single-center observational study including patients undergoing LAAC with Watchman FLX or FLX-Pro between 2022 and 2024. Patients underwent CCT and TEE at 14 days, 45 and 90 days after LAAC. Images were analyzed by three blinded investigators. LAA sealing was classified by four distinct morphological patterns of IDT: Type A: Complete IDT (> 95

BACKGROUND AND AIMS:Life-long direct oral anticoagulant (DOAC) therapy is recommended after catheter ablation for atrial fibrillation (AF) in high-risk patients (CHA2DS2-VA≥2). Long-term DOAC compliance is crucial for effective stroke prevention. This study seeks to evaluate long-term compliance measured by adherence and persistence to DOAC therapy following first-time catheter abltation for AF. METHODS AND RESULTS:All Danish patients undergoing first-time catheter ablation between 2017 and 2024 were identified through Danish registries. Patients were stratified by CHA2DS2-VA score 0, 1, and ≥2. Primary outcomes were adherence and persistence to DOAC therapy at 1, 2, and 3 years after first-time catheter ablation. Adherence was defined as the proportion of days covered (PDC) ≥80%. Persistence was assessed as the proportion of patients covered based on the most recent pharmacy redemption before specific time points, given a 20% grace period. A total of 13 438 patients (32.1% female) were included. At 3 years post-ablation, the proportion of adherent patients with CHA2DS2-VA ≥2 (n = 7322) was 87.6% [95% cinfidence interval (CI): 86.8-88.4]. Applying a sensitivity analysis with a PDC ≥90% threshold, the proportion was 78.8% (95% CI: 77.8-79.8%). Persistence was 73.0% (95% CI: 71.6-74.4%) at 3 years. Rates of thromboembolic outcomes were low with a total incidence rate of the combined outcome of ischaemic stroke, transient ischaemic attack and systemic embolism at 6.6 per 1000 person-years (95% CI: 5.8-7.4). The incidence of major bleeding was found at 7.1 per 1000 person-years (95% CI: 6.3-8.0) for the combined cohort. CONCLUSION:While adherence to DOAC therapy was acceptable in patients with CHA2DS2-VA≥2, persistence declined over time and more than 20% were non-persistent by 3 years. Efforts to improve effective long-term stroke prevention may be warranted. UNSTRUCTURED ABSTRACT:Life-long direct oral anticoagulant (DOAC) therapy is recommended after catheter ablation for atrial fibrillation in high-risk patients (CHA2DS2-VA≥2). Adherence and persistence to DOAC is crucial for effective stroke prevention.Danish patients undergoing first-time catheter ablation between 2017 and 2024 were identified through registries.A total of 13 438 patients were included. At 3 years post-ablation, the proportion of adherent and persistent patients with CHA2DS2-VA ≥2 (n = 7322) was 87.6% and 73.0%, respectively.Adherence to DOAC was acceptable in patients with CHA2DS2-VA≥2. More than 20% of patients were non-persistent by 3 years. Efforts to improve effective long-term stroke prevention may be warranted.

Background The underlying pathophysiology of chronic thromboembolic pulmonary disease (CTEPD) with or without sustained pulmonary hypertension (pH) remains unclear, but repetitive pulmonary emboli (PE) and impaired fibrinolysis are known risk factors. We hypothesized that repetitive PE and inhibition of endogenous fibrinolysis would induce CTEPD with PH (CTEPH). Methods Twenty-four Danish female slaughter pigs of ∼60 kg (4 groups of 6 pigs) were included in the study. Pigs received either autologous PE (PE group), PE plus tranexamic acid (PE + TXA), repetitive PE (day 0, 3, 7, and 10) plus tranexamic acid (REP PE + TXA), or saline infusion (SHAM). Pigs were evaluated at baseline and on day 30 using computed tomography pulmonary angiography (CTPA), invasive hemodynamics, and tissue samples. Results CTPA showed increased pulmonary obstruction score on day 30 in REP PE + TXA group compared to remaining groups (0 ± 0 SHAM vs 31 ± 21 PE vs 42 ± 12 PE + TXA vs 69 ± 17 % REP PE + TXA, P = 0.004). Mean pulmonary arterial pressure was higher in REP PE + TXA group on day 30 than remaining groups (12 ± 2 SHAM vs 13 ± 1 PE vs 12 ± 2 PE + TXA vs 16 ± 2 mmHg REP PE + TXA, P = 0.002) yet none of the groups developed PH and right ventricular function was normalized after 30 days. In histological samples, we found chronic thromboembolic lesions with organized fibrotic thrombi, revascularization, and neointima formation, but no microvascular remodeling. Conclusions Autologous repetitive PE and inhibited fibrinolysis caused chronic thrombi without PH in a porcine model. Our findings suggest that a repetitive PE and impaired endogenous fibrinolysis alone are insufficient to develop CTEPH. Translational aspect This porcine model using autologous pulmonary emboli presents a realistic large animal model of chronic thromboembolic pulmonary disease particularly suitable to further investigate the vascular remodeling after acute PE. Future research should examine the role of inflammation, endothelial dysfunction and angiogenesis-driven clot resolution to improve understanding of the pathophysiological mechanisms.

Pulmonary embolism (PE) increases pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) and may result in right ventricular (RV) failure due to an increase in afterload that exceeds RV compensatory capacity. The ketone body 3-hydroxybutyrate (3-OHB) has been shown to decrease PVR and increase cardiac output (CO) in heart failure and pulmonary hypertension. Effects of 3-OHB in a PE model are unknown. To investigate the effects of intravenous 3-OHB on hemodynamic parameters in a porcine model of acute PE. In an assessor-blinded crossover study, 16 pigs received 3-hour long infusions of 3-OHB and an isoosmolar sodium chloride control solution in randomized order. PE were induced by introducing large autologous blood clots into the pulmonary circulation until the predefined inclusion criterion, a 100% increase in mPAP, was met. Hemodynamic variables were measured hourly. A pulmonary artery catheter was used to measure CO as the primary endpoint using thermodilution, stroke volume (SV), right atrial pressure (RAP), mPAP and vascular resistance across both vascular beds. A pressure-volume catheter was used to measure RV parameters such as end-systolic volume (RVESV), maximal pressure generation rate (dP/dtmax) and end-systolic elastance (Ees). Results were analyzed using a linear mixed model. Embolization of pulmonary arteries increased mPAP by 11 mmHg (P<0.001) and decreased arterial partial pressure of O2 by 4 kPa (P<0.001) with no significant effect on MAP or CO, thus corresponding to an intermediate risk stratum. Infusion of 3-OHB increased CO after 2 hours (1.0 L/min, 95% CI: 0.2 to 1.9 L/min, P=0.031). However, the increase was not significant after 3 hours (0.71 L/min, 95% CI: –0.15 to 1.6 L/min, P=0.13). 3-OHB increased mean systemic arterial pressure, heart rate, and dP/dtmax, compared with control, while significantly decreasing RAP, PVR/SVR-ratio, and RVESV. SV, mPAP and Ees were not significantly altered. In this porcine model of acute PE, 3-OHB did not significantly increase cardiac output after 3 hours. However, RAP, PVR/SVR-ratio and RVESV were reduced, indicating increased contractile function of the RV. Effects on contractility were ambiguous with increased dP/dtmax and unaltered Ees.

BACKGROUND: The optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) remains debated. Ideally, this therapy should effectively prevent device-related thrombosis (DRT) while minimising the associated bleeding risk. AIMS: We aimed to evaluate the long-term safety and efficacy of a postprocedural single antiplatelet therapy (SAPT) strategy following Amplatzer LAAO in a large consecutive cohort. METHODS: This retrospective, single-centre, observational study included all patients discharged on SAPT after LAAO with the Amplatzer Cardiac Plug (ACP) or Amplatzer Amulet between March 2010 and December 2021 at Aarhus University Hospital, Denmark. Baseline, procedural, and imaging data were obtained locally, while clinical outcomes and medication data were extracted from the Danish national health registries. RESULTS: A total of 553 patients underwent Amplatzer LAAO during the specified time frame. Of these, 431 (77.9%) high bleeding risk patients were discharged on SAPT with either acetylsalicylic acid (n=403, 72.9%) or clopidogrel (n=28, 5.1%). At 6 months, 173 (41.7%) patients were not on any antithrombotic therapy. The mean CHA 2 DS 2-VASc and HAS-BLED scores were 3.9 +/- 1.5 and 3.4 +/- 1.1, respectively. DRT was detected in 6 (1.5%) patients on 8-week follow-up imaging using cardiac computed tomography (n=386, 89.6%) or transoesophageal echocardiography (n=27, 6.3%). The 1-year ischaemic stroke rate was 2.2% (95% confidence interval [CI]: 1.14.2). One-year rates for major bleeding and cardiovascular death were 5.9% (95% CI: 4.0-8.9) and 2.9% (95% CI: 1.6-5.1), respectively. CONCLUSIONS: SAPT following Amplatzer LAAO displayed rates of DRT and stroke comparable to those reported with more intensive antithrombotic regimens. Meanwhile, we observed low rates of major bleeding.

BACKGROUND:The exclusion/occlusion of the left atrial appendage (LAA) is a treatment option for atrial fibrillation (AF) patients who are at high risk of stroke and high risk of bleeding. As the role of the LAA is not well understood or explored, this study aims to assess its role on flow dynamics in the left atrium. METHODS:Computational fluid dynamics (CFD) simulations were carried out for nine AF patients before and after LAA exclusion. The flow parameters investigated included the LA velocities, Time Averaged Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), Relative Residence Time (RRT), and Pressure in the LA. RESULTS:This study shows that, on average, a decrease in TAWSS (1.82 ± 1.85 Pa to 1.27 ± 0.96 Pa, p < 0.05) and a slight increase in OSI (0.16 ± 0.10 to 0.17 ± 0.10, p < 0.05), RRT (1.87 ± 1.84 Pa-1 to 2.11 ± 1.78 Pa-1, p < 0.05), and pressure (-19.2 ± 6.8 mmHg to -15.3 ± 8.3 mmHg, p < 0.05) were observed in the LA after the exclusion of the LAA, with a decrease in low-magnitude velocities. CONCLUSION:The exclusion of the LAA seems to be associated with changes in LA flow dynamics. Further studies are needed to elucidate the clinical implications of these changes.

BACKGROUND Device-related thrombosis (DRT) occurs in up to 4% of patients undergoing left atrial appendage occlusion (LAAO) and is associated with substantial morbidity and mortality. However, its pathophysiology, predictors, and optimal management remain unclear. OBJECTIVES This study aims to assess flow dynamic factors correlating to DRT. METHODS A multicenter registry of patients who underwent LAAO and had pre-and post-computed tomography imaging was used. Patient-specific 3-dimensional digital models of the left atrium were created, and finite element simulations were performed to implant an LAAO device into each model in a position that matched the clinical deployment. Computational fluid dynamic simulations were performed to quantify the following flow dynamic parameters: time averaged wall shear stress, oscillatory shear index, and endothelial cell activation potential. RESULTS A total of 38 patients (19 with DRT and 19 without DRT) were included. Left atrium volumes and mitral valve areas were larger in the DRT cohort compared with controls. Patients with DRT had a significantly lower time averaged wall shear stress (1.76 +/- 1.24 Pa vs 2.90 +/- 2.70 Pa), a higher oscillatory shear index (0.19 +/- 0.11 vs 0.17 +/- 0.11), and a higher endothelial cell activation potential (0.23 +/- 0.58 Pa-1 vs 0.17 +/- 0.30 Pa-1) than the controls (P < 0.001 for all). Thrombus locations identified from in-vivo images correlated well with the flow dynamic parameters tested. CONCLUSIONS Flow dynamic parameters may be able to predict the risk of DRT after LAAO. Further investigation with a larger patient cohort and long-term follow-up is needed to assess the role of computational fluid dynamics in the risk stratification of patients considered for LAAO.

Left atrial appendage occlusion (LAAO) is an established alternative to oral anticoagulation for stroke prevention in atrial fibrillation. Antithrombotic therapy is used in the post-procedural period to prevent device-related thrombosis (DRT). The risk of DRT is considered highest in the first 45–90 days after device implantation, based on animal studies of the device healing process. Clinically applied antithrombotic regimens vary greatly across studies, continents, and centers. This article gives an overview of the evidence behind current antithrombotic regimens, ongoing randomized trials, and future post-procedural management.

Acute pulmonary embolism (PE) is a potentially life-threatening condition that causes abrupt obstruction of the pulmonary arteries, leading to acute right heart failure. Novel diagnostic methods and catheter-directed therapies are being developed rapidly, and there is an obvious need for a realistic PE animal model that can be used for pathophysiological evaluation and preclinical testing. This protocol introduces a porcine model employing large autologous pulmonary emboli. Instrumentations are performed with minimally invasive techniques, creating a close-chest model that enables the investigation of various treatment options with high reproducibility. Three hours after drawing blood to create autologous emboli ex vivo, the induction of PE caused an immediate increase in the mean pulmonary arterial pressure (17 ± 3 mmHg to 33 ± 6 mmHg, p < 0.0001) and heart rate (50 ± 9 beats·min-1 to 63 ± 6 beats·min-1, p < 0.0003) accompanied by a decreased cardiac output (5.0 ± 0.8 L/min to 4.5 ± 0.9 L/min, p < 0.037) compared to baseline. The CT pulmonary angiography revealed multiple emboli, and the pulmonary obstruction percentage was increased compared to baseline (0% [0-0] to 57.1% [38.8-63.3], p < 0.0001). In the acute phase, the phenotype is comparable to intermediate-risk PE. The model represents a realistic and well-characterized phenotype of intermediate-risk PE and creates an opportunity to test novel diagnostic methods, interventional and pharmaceutical treatments, and hands-on training for healthcare workers in interventional procedures.

Background Device-related thrombosis (DRT) is a known complication to left atrial appendage closure (LAAC). The surface of a LAAC device should ideally have antithrombotic properties. The novel WATCHMAN FLX Pro (WFP) incorporates a fluoropolymer-coated fabric membrane designed to increase thromboresistance and facilitate endothelialization. Such features could potentially allow for a minimal post-procedural antithrombotic regimen. Radiopaque platinum markers at the device shoulders and a large 40 mm device are other novel features of the WFP.Case summary A 75-year-old man with atrial fibrillation was referred for LAAC due to prior subdural haemorrhage during direct-acting anticoagulation treatment. He underwent the first-in-human WFP implantation as part of the WATCHMAN FLX Pro CT study (NCT05567172). Computed tomography (CT) was used for pre-planning, and the procedure was performed under local analgesia guided by intracardiac echocardiography from the left atrium (LA) without any complications. Post-procedural antithrombotic treatment consisted of acetylsalicylic acid 75 mg/day only, and 45-day CT, transoesophageal echocardiography (TEE), and magnetic resonance imaging demonstrated optimal device position with complete LAAC. Hypoattenuated thickening (6 mm) appeared on the device as a smooth surface in continuity with the left atrial wall on CT and TEE. A specific magnetic resonance T1-weighted scan, used for visualization of fresh thrombus, suggested this to represent tissue ingrowth rather than thrombus.Discussion The advanced follow-up imaging protocol suggested a good WFP implantation result with signs of tissue ingrowth at 45 days. The added radiopaque markers facilitated optimal deployment, evaluation of device stability during tug test, and assessment of device protrusion into the LA.

AIMS:To assess the reproducibility of interpreting hypoattenuated thickening (HAT) and peridevice leak (PDL) using cardiac computed tomography (CT) imaging following Watchman FLX left atrial appendage closure (LAAC). METHODS AND RESULTS:In this multicentre retrospective reproducibility study, 100 anonymized post-LAAC cardiac CT scans were evaluated within the same cardiac phase by an experienced and a novice rater blinded to prior evaluations. All scans were evaluated twice by each rater, assessing overall HAT and PDL categories as well as specific associated findings based on suggested algorithms for post-LAAC interpretation. Inter- and intra-rater agreement and reliability were evaluated using absolute agreement, Cohen's kappa, and Kendall's tau for categorical variables, and mean difference, Bland-Altman plots, limits of agreement (lower and upper), and intra-class correlation coefficients (ICCs) for continuous variables. Within overall categories of both HAT and PDL, substantial agreement (kappa ≥0.61) and reliability (Kendall's tau-b ≥ 0.75) were observed. Specifically, identifying high-grade HAT (kappa ≥0.78) and distal patency (kappa ≥0.85) displayed the highest agreement within HAT and PDL interpretation. Meanwhile, measuring the height of the proximal screw hub cove represented the least reliable HAT assessment among both inter- and intra-rater comparisons (ICC < 0.75), while suspected leak mechanism represented the least reproducible PDL measure. CONCLUSION:Despite only minimal training of one rater, overall high levels of inter- and intra-rater agreement and reliability were observed across the chosen algorithms for interpretation of HAT and PDL following Watchman FLX LAAC. The prognostic implications of the included variables are to be explored in future trials and registries.

Background Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. Methods This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. Results Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. Conclusion In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

OBJECTIVES:. To investigate the contribution of mechanical obstruction and pulmonary vasoconstriction to pulmonary vascular resistance (PVR) in acute pulmonary embolism (PE) in pigs. DESIGN:. Controlled, animal study. SETTING:. Tertiary university hospital, animal research laboratory. SUBJECTS:. Female Danish slaughter pigs (n = 12, ~60 kg). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. PE was induced by infusion of autologous blood clots in pigs. CT pulmonary angiograms were performed at baseline, after PE (first experimental day [PEd0]) and the following 2 days (second experimental day [PEd1] and third experimental day [PEd2]), and clot burden quantified by a modified Qanadli Obstruction Score. Hemodynamics were evaluated with left and right heart catheterization and systemic invasive pressures each day before, under, and after treatment with the pulmonary vasodilators sildenafil (0.1 mg/kg) and oxygen (Fio2 40%). PE increased PVR (baseline vs. PEd0: 178 ± 54 vs. 526 ± 160 dynes; p < 0.0001) and obstruction score (baseline vs. PEd0: 0% vs. 45% ± 13%; p < 0.0001). PVR decreased toward baseline at day 1 (baseline vs. PEd1: 178 ± 54 vs. 219 ± 48; p = 0.16) and day 2 (baseline vs. PEd2: 178 ± 54 vs. 201 ± 50; p = 0.51). Obstruction score decreased only slightly at day 1 (PEd0 vs. PEd1: 45% ± 12% vs. 43% ± 14%; p = 0.04) and remained elevated throughout the study (PEd1 vs. PEd2: 43% ± 14% vs. 42% ± 17%; p = 0.74). Sildenafil and oxygen in combination decreased PVR at day 0 (–284 ± 154 dynes; p = 0.0064) but had no effects at day 1 (–8 ± 27 dynes; p = 0.4827) or day 2 (–18 ± 32 dynes; p = 0.0923). CONCLUSIONS:. Pulmonary vasoconstriction, and not mechanical obstruction, was the predominant cause of increased PVR in acute PE in pigs. PVR rapidly declined over the first 2 days after onset despite a persistent mechanical obstruction of the pulmonary circulation from emboli. The findings suggest that treatment with pulmonary vasodilators might only be effective in the acute phase of PE thereby limiting the window for such therapy.

Left atrial appendage occlusion (LAAO) is rapidly growing as valid stroke prevention therapy in atrial fibrillation. Cardiac imaging plays an instrumental role in preprocedural planning, procedural execution, and postprocedural follow-up. Recently, cardiac computed tomography (CCT) has made significant advancements, resulting in increasing use both preprocedurally and in outpatient follow-up. It provides a noninvasive, high-resolution alternative to the current standard, transesophageal echocardiography, and may display advantages in both the detection and characterization of device-specific complications, such as peridevice leak and device-related thrombosis. The implementation of CCT in the follow-up after LAAO has identified new findings such as hypoattenuated thickening on the atrial device surface and left atrial appendage contrast patency, which are not readily assessable on transesophageal echocardiography. Currently, there is a lack of standardization for acquisition and interpretation of images and consensus on definitions of essential findings on CCT in the postprocedural phase. This paper intends to provide a practical and standardized approach to both acquisition and interpretation of CCT after LAAO based on a comprehensive review of the literature and expert consensus among European and North American interventional and imaging specialists.