Hospitalization of Symptomatic Patients With Heart Failure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2.

BACKGROUND: For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results. OBJECTIVES: This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER. METHODS: RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25 cm2; 14% >0.40 cm2, 23% <0.20 cm2) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n = 333) with a HF hospitalization in the 12 months before randomization. RESULTS: At 24 months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95% CI: 0.49-0.85; P = 0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.57-0.99; P = 0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95% CI: 0.57-0.95; P = 0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95% CI: 0.58-0.99; P = 0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95% CI: 0.63-1.07; P = 0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95% CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P < 0.0001, and 1,067 vs 1,776 total days lost; P < 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30 days and at 6, 12, and 24 months of follow-up (P < 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (Pinteraction = 0.03) and of recurrent HF hospitalizations within 24 months (Pinteraction = 0.06). CONCLUSIONS: These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF.

Does atrial fibrillation still increase the risk of death? One-year follow-up results of the NOMED-AF study.

INTRODUCTION: Although atrial fibrillation (AF) is a well­known risk factor for ischemic stroke and hospitalization, its effect on mortality has not been clearly established. OBJECTIVES: We aimed to assess whether AF is an independent risk factor for death. A secondary objective was to evaluate the role of oral anticoagulation in the prevention of stroke and death in 1­year follow­up of patients included in the NOMED­AF (Noninvasive Monitoring for Early Detection of Atrial Fibrillation) study. PATIENTS AND METHODS: The NOMED­AF study included 3014 patients. The participants underwent continuous long­term electrocardiographic monitoring using a wearable vest for up to 30 days. The present analysis involved 2795 patients who completed the 1­year follow­up. The median (interquartile range) follow­up time was 365 (365-365) days. AF was diagnosed in 617 participants. RESULTS: Independent risk factors for death in the patients who completed the 1­year follow­up were AF, age equal to or above 65 years, and chronic kidney disease. The individuals with diagnosed AF had an almost 2­fold higher risk of death (odds ratio [OR], 1.7; 95% CI, 1.18-2.44; P <0.001) and a 2.5­fold higher risk of stroke (OR, 2.53; 95% CI, 1.41-4.44; P <0.001), as compared with those without an AF diagnosis. The participants with AF who received oral anticoagulants had an almost 5­fold lower risk of death than those who were not on anticoagulation (2.9% vs 14.2%, respectively; P <0.001). CONCLUSIONS: AF is an independent risk factor for death and cardiovascular hospitalization. The risk of death and stroke in patients with AF is significantly higher than in the patients without this arrhythmia. Oral anticoagulation in patients with AF significantly reduces the rates of death and stroke; however, its use is suboptimal in this group of patients.

Anticoagulants versus Left Atrial Appendage Occlusion in Patients with Atrial Fibrillation and Co-Morbid Thrombocytopenia.

Left atrial appendage closure (LAAC) is an alternative approach to anticoagulants. Nonetheless, data regarding the outcomes of LAAC procedures in patients with thrombocytopenia remain lacking. The primary objective was to determine the incidence of the composite endpoint comprising ischemic stroke, intracranial hemorrhage, major bleeding, and cardiac cause of death among patients with atrial fibrillation (AF) and thrombocytopenia who were either undergoing LAAC or receiving oral anticoagulants. The secondary endpoint was the determination of total mortality. Data from a prospective, single-center registry of patients undergoing LAAC procedures were analyzed. A subset of 50 consecutive patients with thrombocytopenia were selected. Thrombocytopenia was defined as a thrombocyte count below 150,000. Subsequently, from patients hospitalized with AF receiving oral anticoagulants, 50 patients were further chosen based on propensity score matching, ensuring comparability with the study group. The primary endpoint occurred in 2% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.097). Additionally, a significant difference was noted in the occurrence of the secondary endpoint, which was observed in 0% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.025). In patients with thrombocytopenia the LAAC procedure improves prognosis compared with continued anticoagulant treatment.

Rationale and design of a randomized clinical trial evaluating the efficacy of mechanical neuroprotection in reducing the risk of silent brain infarcts associated with percutaneous left atrial appendage closure: study protocol for a LAAC-SBI trial.

BACKGROUND: Left atrial appendage closure (LAAC) procedures prevent cardioembolic stroke in patients with atrial fibrillation who have contraindications to oral anticoagulant medications. However, these procedures carry certain risks of peri-procedural complications. One such complication is silent brain infarcts (SBI), which can lead to cognitive impairment and mood disturbances. The implementation of mechanical neuroprotection systems during LAAC procedures may reduce the risk of SBI and associated cognitive and mood disorders. METHODS: The LAAC-SBI trial is a prospective, multicenter, randomized, and double-blind interventional study. The study aims to enroll a total of 240 patients, with 120 patients allocated to each group. The study group will evaluate the use of the Sentinel CPS during LAAC, while the control group will undergo LAAC procedures without the Sentinel CPS. The primary endpoint of the study is the number of new SBIs or stroke foci detected by diffusion-weighted magnetic resonance imaging (DW MRI). Secondary endpoints include deterioration of cognitive function, development of dementia syndrome, and occurrence of depressive disorders. These endpoints will be assessed using questionnaire tools such as the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), Controlled Oral Word Association Test (COWAT), and Hospital Anxiety and Depression Scale (HADS). The observational period for patients in the study is 2 years. DISCUSSION: If the study demonstrates a favorable outcome with reduced incidence of SBI and improved cognitive and mood outcomes in patients receiving cerebral protection devices during LAAC, it will have significant implications for clinical management standards. This would support the use of neuroprotection devices not only for LAAC but also in procedures such as atrial fibrillation ablation or transcatheter mitral valve interventions, where the risk of embolic events and subsequent brain injury may also be present. TRIAL REGISTRATION: ClinicalTrials.gov NCT05369195. Registration on 11.05.2022.

Predictive factors of left ventricular ejection fraction improvement after myocardial infarction treated invasively.

Introduction: One indication for the implantation of a cardioverter-defibrillator is a reduction in the left ventricular ejection fraction (LVEF) ≤ 35%. However, in certain patients following an acute myocardial infarction (AMI) a gradual improvement in LVEF has been observed. The factors determining this increase in LVEF have not been conclusively determined. Aim: To ascertain the independent predictors associated with the improvement of LVEF in patients following AMI who underwent invasive treatment, while observing their progress over a 6-month follow-up period. Material and methods: Among 665 patients with AMI, a population with LVEF ≤ 35% was selected. After 6 months, a follow-up echocardiogram was performed. Further analysis compared patients with at least 5% improvement in LVEF (Group I) with those without an increase (Group II). Results: Group I consisted of 34 individuals out of 80 patients (43%) with LVEF ≤ 35%. The factors linked to a reduced probability of LVEF improvement were: higher levels of cardiac troponin T (cTnT) (OR 0.841 for 1 ng/ml increase in cTnT, CI 0.715-0.989; p = 0.037), presence of diabetes mellitus (OR = 0.217, 95% CI: 0.058-0.813, p = 0.023) and moderate or severe mitral regurgitation (OR = 0.178, 95% CI: 0.053-0.597; p = 0.005). Conclusions: The study findings indicate that the presence of severe or moderate mitral regurgitation is the most significant factor contributing to the lack of LVEF improvement following AMI. Moreover, the extent of myocardial damage, as indicated by elevated cTnT values, along with compromised adaptation to hypoxia in patients with diabetes, are identified as independent factors associated with reduced chances of an increase in LVEF.

ECHOCARDIOGRAPHIC METHODS FOR ASSESSING LEFT VENTRICULAR SYSTOLIC FUNCTION.

Transthoracic echocardiography (TTE) is the recommended primary method of assessing cardiac function. The measurement of LVEF determines the strategy for treatment of patients, as well as influences their prognosis. 3D echocardiography has higher accuracy and reproducibility than 2D echocardiography; hence it is currently recommended for volume and LVEF measurements. New echocardiographic techniques: global longitudinal strain measured by speckle tracking and myocardial work allow earlier detection of myocardial abnormalities. In addition, they have greater sensitivity in detecting ischemia, fibrosis and left ven¬tricular systolic dyssynchrony. In some myocardial pathologies, such as amyloidosis, hypertrophic cardiomyopathy or Chagas disease, we observe characteristic patterns of myocardial deformation (strain), which are their hallmarks. Myocardial work, on the other hand, allows assessment of contractility independent of the effect of afterload. The new echocardiographic techniques provide additional diagnostic tools for assessing left ventricular systolic function and informa¬tion on prognosis, and hence their use can be expected to become more widespread in daily clinical practice.

The effectiveness of atrial fibrillation identification using noninvasive long-term electrocardiographic monitoring system (NOMED-AF TECH).

INTRODUCTION: Although it is well­known that longer electrocardiographic (ECG) monitoring allows for detection of paroxysmal silent atrial fibrillation (SAF), it is still unknown how long the ECG monitoring should last to increase the probability of SAF diagnosis. OBJECTIVES: Our aim was to analyze ECG acquisition parameters and timing to detect SAF during the Noninvasive Monitoring for Early Detection of Atrial Fibrillation study. PATIENTS AND METHODS: The protocol assumed up to 30 days of ECG telemonitoring of each participant in order to reveal AF / atrial flutter (AFL) episodes lasting at least 30 seconds. SAF was defined as AF detected and confirmed by cardiologists in asymptomatic individuals. The ECG signal analysis was based on the results of 2974 participants (98.67%). AF/AFL episodes were registered and confirmed by cardiologists in 515 individuals, that is, 75.7% of all patients (n = 680) in whom AF/AFL diagnosis was established. RESULTS: The median monitoring time to detect the first SAF episode was 6 days (interquartile range [IQR], 1-13). Fifty percent of the patients with this type of arrhythmia were identified by 6th day (IQR, 1-13) of the monitoring, and 75% by the 13th day of the study. Paroxysmal AF was registered on average on 4th day (IQR, 1-10). CONCLUSIONS: The ECG monitoring time to detect the first episode of SAF in at least 75% of patients at risk of this arrhythmia was 14 days. Detection of 1 patient with de novo AF, SAF, or de novo SAF, required monitoring of, respectively, 17, 11, and 23 patients.

TRIMETHYLAMINE OXIDE - FACTOR IN THE DEVELOPMENT OF ATHEROSCLEROSIS AND A POTENTIAL TARGET FOR DIETARY AND PHARMACOLOGICAL INTERVENTIONS.

Atherosclerotic Cardiovascular Diseases (ASCVD) are the most common cause of death worldwide. Among the well-known con¬tributors to atherosclerosis are less common ones, such as trimethylamine oxide (TMAO). This substance is formed from the oxida¬tion of trimethylamine (TMA) with the participation of flavin oxidases in the liver. TMA is produced with the involvement of the intestinal microbiota from foods rich in choline and carnitine. TMAO promotes the production of foam cells, enhances platelet aggregation, affects endothelial inflammation, and promotes atherosclerosis development. However, further research is needed to determine the effect of dietary changes on reducing TMAO levels and thus reducing incident ASCVD.

Long-term results of percutaneous left atrial appendage occlusion in patients with atrial fibrillation and chronic kidney disease.

Introduction: The coexistence of atrial fibrillation (AF) and chronic kidney disease (CKD) increases the risk of thromboembolic complications, as well as hemorrhagic incidents - percutaneous left atrial appendage occlusion (LAAO) is an alternative. Aim: To evaluate the long-term outcomes of LAAO performed in patients with CKD and non-valvular AF. Material and methods: Two hundred and seventy-two patients with AF who underwent LAAO between 2009 and 2019 were prospectively analyzed. Patients were divided into two groups: CKD (105 patients) and non-CKD (167 patients) (cut-off point: eGFR 60 ml/min/1.73 m2). The mean follow-up period was 25.56 months. Results: The LAAO was successful in 269 (98.9%) patients. Seven (2.6%) patients suffered an ischemic stroke, including 2 (1.9%) with CKD and 5 (3.0%) in the non-CKD (p = 0.581) group. The risk of ischemic stroke was 0.25/100 patient-years (PY) for CKD and 0.39/100 PY for the non-CKD (p =0.028) group. The LAAO was associated with a relative risk reduction (RRR) of 96.4% (CKD group) and 91.8% (non-CKD group) on average compared to expected stroke rates. Hemorrhagic stroke occurred in 1 (0.6%) patient of the non-CKD group, whereas major bleeding occurred in 1 (0.6%) non-CKD patient and 1 (1.0%) CKD patient (p = 0.427). The risk of major bleeding was 0.13/100 PY for CKD and 0.15/100 PY for non-CKD (p = 0.768), corresponding to an RRR of 97.9% (CKD) and 97.4% (non-CKD) on average compared to oral anticoagulant therapy. Conclusions: Considering the significant reduction in thromboembolic events, with a simultaneous reduction of major bleeding complications, LAAO is a safe and effective alternative for AF patients with CKD.

The prognostic impact of therapeutic hypothermia after a sudden cardiac arrest in the course of myocardial infarction.

BACKGROUND: Mild therapeutic hypothermia (MTH) is one of the treatment methods recommended in post-sudden cardiac arrest (SCA) patients who remain unconscious after cardiopulmonary resuscitation. The present study aimed at assessing the prognostic impact of intravascular MTH on invasively treated patients with an acute myocardial infarction complicated by SCA. METHODS: The presented data were collected via a single-center retrospective analysis of the hospitalization and follow-up of 54 patients with post-myocardial infarction complicated by SCA. The patients were treated in the years 2014-2020 and the average follow-up period was 1141 ± 163 days. The population was divided into two groups: 28 patients treated with MTH (a therapeutic hypothermia [TH] group) and 26 patients treated without MTH (a non-TH group). RESULTS: The results indicate a trend toward improved in-hospital prognosis in the TH group, but the differences did not reach statistical significance: TH 25.0% vs. non-TH 34.5%, p = 0.554. An additional analysis of younger patients (under 60 years of age) revealed no significant differences between the TH and non-TH subgroups concerning in-hospital survival (in-hospital mortality rate: TH 6.7% vs. non-TH 30.0%, p = 0.267). Still, TH patients aged < 60 achieved a significantly better rate of follow-up survival (p = 0.041). The older (≥ 60) patient group showed no in-hospital mortality rate differences (TH 46.2% vs. non-TH 37.5%, p = 0.638). However, in-hospital bleeding frequency was significantly higher in patients aged ≥ 60 from the hypothermia group (TH 50.0% vs. non-TH 6.7%, p = 0.011). CONCLUSIONS: Intravascular MTH may improve the follow-up prognosis in patients aged < 60 with SCA in the early phase of myocardial infarction.

Long-term outcomes in patients after left atrial appendage occlusion: The results from the LAAO SILESIA registry.

BACKGROUND: The benefits of oral anticoagulation (OAC) therapy are undeniable. However, such treatment is contraindicated in 2%-10% of patients. According to the latest guidelines, percutaneous left atrial appendage occlusion (LAAO) may be considered in stroke prevention. AIMS: We analyzed the data of patients from the Polish population, who had undergone LAAO procedures in the Silesian Province based on limited reports. METHODS: The data from the SILCARD database of all patients who underwent LAAO between 2006 and 2019, and the data from the databases of the centers performing the procedures in the Silesian Province were included in the LAAO SILESIA registry. We analyzed the efficacy and safety of the procedure and its relationship with the occurrence of stroke and bleeding in the post-hospital follow-up. RESULTS: We analyzed 649 patients with the mean values of CHA2DS2-VASc and HAS-BLED scores of 4.1 and 3.2, respectively. The predominant indication for LAAO was a history of bleeding during OAC. The most frequent in-hospital major adverse cardiac events were anemia, which required blood transfusion (5.5%), and pericardial effusion, which was treated either conservatively (0.9%) or interventionally (1.2%). During hospitalization, stroke was detected in 4 patients and three patients died of any cause. LAAO reduced the annual risk of stroke by 84% and the annual risk of bleeding by 27%. CONCLUSIONS: Based on a "real-life" cohort of patients from the Silesian Province, we concluded that LAAO is related to low in-hospital major cardiovascular adverse events. In the long-term follow-up, LAAO reduced the rates of stroke and bleeding.

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

OBJECTIVE: Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. METHODS: This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. RESULTS: IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). CONCLUSION: In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up.

Predicting Silent Atrial Fibrillation in the Elderly: A Report from the NOMED-AF Cross-Sectional Study.

BACKGROUND: Silent atrial fibrillation (SAF) is common and is associated with poor outcomes. AIMS: to study the risk factors for AF and SAF in the elderly (≥65 years) general population and to develop a risk stratification model for predicting SAF. METHODS: Continuous ECG monitoring was performed for up to 30 days using a vest-based system in a cohort from NOMED-AF, a cross-sectional study based on a nationwide population sample. The independent risk factors for AF and SAF were determined using multiple logistic regression. ROC analysis was applied to validate the developed risk stratification score. RESULTS: From the total cohort of 3014 subjects, AF was diagnosed in 680 individuals (mean age, 77.5 ± 7.9; 50.1% men) with AF, and, of these, 41% had SAF. Independent associations with an increased risk of AF were age, male gender, coronary heart disease, thyroid diseases, prior ischemic stroke or transient ischemic attack (ICS/TIA), diabetes, heart failure, chronic kidney disease (CKD), obesity, and NT-proBNP >125 ng/mL. The risk factors for SAF were age, male gender, ICS/TIA, diabetes, heart failure, CKD, and NT-proBNP >125 ng/mL. We developed a clinical risk scale (MR-DASH score) that achieved a good level of prediction in the derivation cohort (AUC 0.726) and the validation cohort (AUC 0.730). CONCLUSIONS: SAF is associated with various clinical risk factors in a population sample of individuals ≥65 years. Stratifying individuals from the general population according to their risk for SAF may be possible using the MR-DASH score, facilitating targeted screening programs of individuals with a high risk of SAF.

Percutaneous Occlusion of the Left Atrial Appendage with Thrombus Irresponsive to Antithrombotic Therapy.

We analyzed clinical experience with percutaneous closure of instances of left atrial appendage with thrombus (LAAT) irresponsive to antithrombotic therapy in patients treated in three high-volume cardiology centers. Clinical and procedural data regarding consecutive patients who underwent percutaneous left atrial appendage closure (PLAAC) due to LAAT were retrospectively analyzed. The study population consisted of 17 patients (11 men; 68 ± 14 years; CHA2DS2VASC 4.7 ± 1.9; HASBLED 3 (0-5)) with LAAT confirmed by transesophageal echocardiography, and included 5 patients with mechanical heart valves. Most of the patients (94.1%) received anticoagulation therapy before PLAAC. All LAATs were located in distal portions of the appendage and occupied less than 30% of its volume. Occluding-device implantation was successful in 17 patients; in one, a residual leak was disclosed. Appropriate positioning of occluders required more than 1 attempt in 6 individuals (35.3%); in 3 others (17.6%), the subjects' devices had contact with thrombi. No procedural complications were noted. Midterm follow-up (median: 10 months) revealed no procedure-related complications or clinically diagnosed thromboembolism. Transesophageal echocardiography (TEE) performed after six months revealed device-related thrombus in one patient. We concluded that LAAT irresponsive to antithrombotic therapy might be effectively treated with PLAAC, even in patients with mechanical-valve prostheses.

The Extended Utility of CHA2DS2VASc and HAS-BLED Scores in the Selection for Transcutaneous Left Atrial Appendage Closure.

BACKGROUND AND PURPOSE: Left atrial appendage closure (LAAC) is an option for stroke prevention in atrial fibrillation patients. Randomized studies have demonstrated the effectiveness and safety of LAAC but included patients with an average risk of stroke and bleeding complications. The current study aimed to assess the extended utility of CHA2DS2VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; age 65 to 75 years; and sex category) and HAS-BLED (hypertension; abnormal renal/liver function; stroke; bleeding history or predisposition; labile INR, elderly, drugs/alcohol concomitantly) scores for qualification and prognosis after LAAC. METHODS: The study population comprised 270 patients aged 72.8 ± 8.78 years. The occluders used were the Amplatzer Amulet (N = 205), Amplatzer Cardiac Plug (N = 53), and Watchman device (N = 12). The prognosis after LAAC was analyzed for different cohorts of patients distinguished based on different CHA2DS2VASc and HAS-BLED scores. The mean duration of follow-up was 21.6 ± 10.3 months. RESULTS: The observed rates of ischemic stroke and bleeding were much lower than that expected (2.2% vs. 5.6%, and 0.76% vs. 6.05%, respectively). The mortality rate did not differ concerning the CHA2DS2CVASc score. It was significantly lower (8.3%) for HAS-BLED < 3, and it raised to 17.9% for HAS-BLED = 3 and to 25.9% for HAS-BLED > 3. Significant differences (p = 0.003) occurred for Kaplan-Meier curves for extreme HAS-BLED subgroups. A composite endpoint was most often found in high/very high risk of bleeding patients. CONCLUSIONS: HAS-BLED, but not CHA2DS2CVASc score, may be a useful tool to predict the prognosis of patients after LAAC. Qualification for LAAC based on the risk of stroke should not differ from qualification for anticoagulation. Despite the worse prognosis of patients with the highest bleeding risk, this group is likely to experience the greatest benefit from reducing the bleeding risk from LAAC.