Impact of cerebral protection on observed versus predicted in-hospital stroke in a high stroke risk TAVR cohort.

BACKGROUND: Despite impressive improvements in the safety profile of Transcatheter aortic valve replacement (TAVR), the risk for peri-procedural stroke after TAVR has not declined substantially. In an effort to reduce periprocedural stroke, cerebral embolic protection (CEP) devices have been utilized but have yet to demonstrate benefit in all-comers. There is a paucity of data supporting the utilization of CEP in TAVR patients with an anticipated high risk for peri-procedural stroke. METHODS: The Transcatheter Aortic Valve Replacement In-Hospital Stroke (TASK) score is a clinical risk tool for predicting the in-hospital stroke risk of patients undergoing transfemoral TAVR. This score was used to identify high-risk patients and calculate the expected in-hospital stroke risk. This was a single-centre cohort study in all consecutive TAVR patients who had placement of CEP. The observed versus expected ratio for peri-procedural stroke was calculated. To obtain 95% credible intervals, we used 1000 bootstrapped samples of the original cohort sample size without replacement and recalculated the TASK predicted scores. RESULTS: The study included 103 patients. The median age was 83 (IQR 78,89). 63 were male (61.1%) and 45 (43.69%) had a history of previous Stroke or TIA. Two patients had an in-hospital stroke after TAVR (1.94%). The expected risk of in-hospital stroke based on the TASK score was 3.39% (95% CI 3.07-3.73). The observed versus expected ratio was 0.57 (95% CI 0.52-0.64). CONCLUSION: In this single-center study, we found that in patients undergoing TAVR with high stroke risk, CEP reduced the in-hospital stroke risk by 43% when compared with the risk-score predicted rate. CLINICAL TRIAL NUMBER: N/A.

Position Statement on Cardiac Computed Tomography Following Left Atrial Appendage Occlusion.

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.

Impact of aspirin dose according to race in secondary prevention of atherosclerotic cardiovascular disease: a secondary analysis of the ADAPTABLE randomised controlled trial.

OBJECTIVES: To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD). DESIGN: A secondary analysis of the randomised controlled trial ADAPTABLE was performed. SETTING: The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA. PARTICIPANTS: Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%). INTERVENTIONS: Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion. RESULTS: Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints. CONCLUSION: Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race. TRIAL REGISTRATION NUMBER: NCT02697916.

Benefits of intensive lipid-lowering therapies in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS. METHODS: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes. RESULTS: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p = 0.057). CONCLUSIONS: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.

Outcomes and Predictors of Stroke After Transcatheter Aortic Valve Replacement in the Cerebral Protection Device Era.

BACKGROUND: Studies have shown inconclusive results on the effectiveness of cerebral protection devices (CPDs) with transcatheter aortic valve replacement. We aimed to analyze the national statistics on stroke and other outcomes with CPD use. METHODS AND RESULTS: The Nationwide Readmissions Database (2017-2020) was queried to obtain data on patients undergoing transcatheter aortic valve replacement. Outcomes were compared between patients with a CPD and patients without a CPD. Of 271 804 patients undergoing transcatheter aortic valve replacement, CPD was used in 7.3% of patients. In a multivariable logistic regression analysis, CPD use was not associated with lower overall stroke rates (1.6% versus 1.9% without CPD; odds ratio, 0.95 [95% CI, 0.84-1.07]; P=0.364), but it was significantly associated with lower major stroke rates (1.2% versus 1.5% without CPD; odds ratio, 0.85 [95% CI, 0.74-0.98]; P=0.02). Patients with a CPD also had a shorter length of stay, higher routine discharges to home/self-care (74.9% versus 70.6%), and lower mortality rates (0.7% versus 1.3%). The 30-day (9.6% versus 11.7%) and 180-day (24.6% versus 28.2%) readmission rates were significantly lower in the CPD cohort. Among patients who developed stroke, patients with a CPD had more frequent routine discharges. Prior valve surgery was associated with the highest risk of overall and major stroke. CONCLUSIONS: CPD use during transcatheter aortic valve replacement was not independently associated with a lower risk of overall stroke but was associated with a lower risk of major stroke in a multivariable model. Data from future randomized trials that may offset any potential confounders in our study are required to help identify patients who would benefit from the use of these devices.

Physical activity modification following a Transient Ischemic Attack in individuals with diabetes.

BACKGROUND: Individuals with diabetes exhibit a higher risk of cardiovascular disease and mortality compared to healthy individuals. Following a transient ischemic attack (TIA) the risk of stroke and death increase further. Physical activity engagement after a TIA is an effective way of secondary prevention. However, there's a lack of research on how individuals with diabetes modify physical activity levels and how these adjustments impact survival post-TIA. This study aimed to determine the extent to which individuals with diabetes alter their physical activity levels following a TIA and to assess the impact of these changes on mortality. METHODS: This was a nationwide longitudinal study, employing data from national registers in Sweden spanning from 01/01/2003 to 31/12/2019. Data were collected 2 years retro- and prospectively of TIA occurrence, in individuals with diabetes. Individuals were grouped based on decreasing, remaining, or increasing physical activity levels after the TIA. Cox proportional hazards models were fitted to evaluate the adjusted relationship between change in physical activity and all-cause, cardiovascular, and non-cardiovascular mortality. RESULTS: The final study sample consisted of 4.219 individuals (mean age 72.9 years, 59.4% males). Among them, 35.8% decreased, 37.5% kept steady, and 26.8% increased their physical activity after the TIA. A subsequent stroke occurred in 6.7%, 6.4%, and 6.1% of individuals, while death occurred in 6.3%, 7.3%, and 3.7% of individuals, respectively. In adjusted analyses, participants who increased their physical activity had a 45% lower risk for all-cause mortality and a 68% lower risk for cardiovascular mortality, compared to those who decreased their physical activity. CONCLUSIONS: Positive change in physical activity following a ΤΙΑ was associated with a reduced risk of mortality. Increased engagement in physical activity should be promoted after TIA, thereby actively supporting individuals with diabetes in achieving improved health outcomes.

Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

BACKGROUND: Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear. METHODS AND RESULTS: Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]). CONCLUSIONS: These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.

Left Atrial Appendage Closure Compared With Oral Anticoagulants for Patients With Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) has been suggested as an alternative to long-term oral anticoagulation for nonvalvular atrial fibrillation, but comparative data remain scarce. We aimed to assess ischemic and bleeding outcomes of LAAC compared with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for the prevention of cardioembolic events in patients with atrial fibrillation. METHODS AND RESULTS: Embase and MEDLINE were searched for randomized trials comparing LAAC, VKAs, and DOACs. The primary efficacy end point was any stroke or systemic embolism. Treatment effects were calculated from a network meta-analysis and ranked according to the surface under the cumulative ranking curve. Seven trials and 73 199 patients were included. The risk of the primary end point was not statistically different between LAAC versus VKAs (odds ratio [OR], 0.92 [95% CI, 0.62-1.50]) and LAAC versus DOACs (OR, 1.11 [95% CI, 0.71-1.73]). LAAC and DOACs resulted in similar risk of major or minor (OR, 0.93 [95% CI, 0.61-1.42]) and major bleeding (OR, 0.92 [95% CI, 0.58-1.46]); however, after exclusion of procedural bleeding, bleeding risk was significantly lower in those undergoing LAAC. Both LAAC and DOACs reduced the risk of all-cause death  compared with VKAs (LAAC versus VKAs: OR, 0.70 [95% CI, 0.53-0.91]; DOACs versus VKAs: OR, 0.90 [95% CI, 0.85-0.95], respectively). DOACs ranked as the best treatment for stroke or systemic embolism prevention (66.9%) and LAAC for reducing major bleeding (63.9%) and death (96.4%). CONCLUSIONS: As a nonpharmacological alternative to oral anticoagulation for atrial fibrillation, LAAC showed similar efficacy and safety compared with VKAs or DOACs. Prospective confirmation from larger studies is warranted.

A comparison of simplified or conventional antithrombotic regimens after left atrial appendage closure in patients at high bleeding risk: the PLATEBRISK study.

BACKGROUND: Antithrombotic treatment (ATT) post-left atrial appendage occlusion (LAAO) remains controversial. Furthermore, most of the patients undergoing LAAO are at a very high bleeding risk. AIMS: This study aimed to compare a simplified versus conventional ATT after LAAO in very high bleeding risk patients. METHODS: This is a multicentre, retrospective study including very high bleeding risk patients, according to the Bleeding Academic Research Consortium (BARC) definition, who underwent LAAO. These included patients at >4% risk of BARC 3 to 5 bleeding or >1% risk of intracranial bleeding after the procedure. Two groups were established based on the discharge ATT. The simplified group included single antiplatelet treatment or no treatment, and the conventional group comprised dual antiplatelet treatment or anticoagulation (combined or not with antiplatelet therapy). RESULTS: A total of 1,135 patients were included. The mean CHA2DS2-VASc and HAS-BLED scores were 4.5±1.5 and 3.7±1.0, respectively. There were no differences in the composite endpoint (death, stroke, transient ischaemic attack, device-related thrombus or major bleeding) between the 2 groups (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.59-1.11; p=0.188). Although the rate of major bleeding during the first year was numerically lower in the simplified group, it did not reach statistical significance (HR 0.67, 95% CI: 0.41-1.10; p=0.104). Nonetheless, patients with previous major bleeding presented a significantly lower rate of major bleeding when using the simplified treatment (HR 0.61, 95% CI: 0.36-0.99; p=0.049). CONCLUSIONS: In patients with very high bleeding risk, a simplified ATT after LAAO seems to be as effective as conventional protocols. Furthermore, patients with a history of major bleeding experienced a lower risk of major bleeding with the simplified ATT.

Determinants of adverse outcomes following patent foramen ovale closure in elderly patients.

BACKGROUND: Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly. AIMS: Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events. METHODS: This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted. RESULTS: A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF. CONCLUSIONS: Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population.

Safety and effectiveness of left atrial appendage closure in atrial fibrillation patients with different types of heart failure.

BACKGROUND: Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF. METHODS: Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF < 50%, HFrEF) group and HF with preserved ejection fraction (LVEF ≥ 50%, HFpEF) group. The data we collected from patients included: gender, age, comorbid diseases, CHA2DS2-VASc score, HAS-BLED score, NT-proBNP level, residual shunt, cardiac catheterization results, occluder size, postoperative medication regimen, transthoracic echocardiography (TTE) results and transesophageal echocardiography (TEE) results, etc. Patients were followed up for stroke, bleeding, device related thrombus (DRT), pericardial tamponade, hospitalization for HF, and all-cause death within 2 years after surgery. Statistical methods were used to compare the differences in clinical outcome of LAAC in AF patients with different types of HF. RESULTS: Overall, 288 NVAF patients with HF were enrolled in this study, including 142 males and 146 females. There were 74 patients in the HFrEF group and 214 patients in the HFpEF group. All patients successfully underwent LAAC. The CHA2DS2-VASc score and HAS-BLED score of HFrEF group were lower than those of HFpEF group. A total of 288 LAAC devices were implanted. The average diameter of the occluders was 27.2 ± 3.5 mm in the HFrEF group and 26.8 ± 3.3 mm in the HFpEF group, and there was no statistical difference between the two groups (P = 0.470). Also, there was no statistically significant difference in the occurrence of residual shunts between the two groups as detected by TEE after surgery (P = 0.341). LVEF was significantly higher in HFrEF group at 3 days, 3 months and 1 year after operation than before (P < 0.001). At 45-60 days after surgery, we found DRT in 9 patients and there were 4 patients (5.4%) in HFrEF group and 5 patients (2.3%) in HFpEF group, with no significant difference between the two groups (P = 0.357). One patient with DRT had stroke. The incidence of stroke was 11.1% in patients with DRT and 0.7% in patients without DRT (P = 0.670). There was one case of postoperative pericardial tamponade, which was improved by pericardiocentesis at 24 h after surgery in the HFpEF group, and there was no significant difference between the two groups (P = 1.000). During a mean follow-up period of 49.7 ± 22.4 months, there were no significant differences in the incidence of stroke, bleeding, DRT and HF exacerbation between the two groups. We found a statistical difference in the improvement of HF between HFrEF group and HFpEF group (P < 0.05). CONCLUSIONS: LAAC is safe and effective in AF patients with different types of HF. The improvement of cardiac function after LAAC is more pronounced in HFrEF group than in HFpEF group.

Incidence and predictors of 2-year mortality following percutaneous left atrial appendage occlusion in the EWOLUTION trial.

AIMS: Sufficient survival time following left atrial appendage occlusion (LAAO) is essential for ensuring the efficacy and cost-effectiveness of this strategy for stroke prevention. Understanding prognostic factors for early mortality after LAAO could optimize patient selection. In the current study, we perform an in-depth analysis of 2-year mortality after LAAO, focusing particularly on potential predictors. METHODS AND RESULTS: The EWOLUTION registry is a real-world cohort comprising 1020 patients that underwent LAAO. Endpoint definitions were pre-specified, and death was categorized as cardiovascular, non-cardiovascular, or unknown origin. Mortality rates were calculated from Kaplan-Meier estimates. Baseline characteristics significantly associated with death in univariate Cox regression analysis were incorporated into the multivariate analysis. All multivariate predictors were included in a risk model. Two-year mortality rate was 16.4% [confidence interval (CI): 14.0-18.7%], with 50% of patients dying from a non-cardiovascular cause. Multivariate baseline predictors of 2-year mortality included age [hazard ratio (HR) 1.05, CI: 1.03-1.08, per year increase], heart failure (HR 1.73, CI: 1.24-2.41), vascular disease (HR 1.47, CI: 1.05-2.05), valvular disease (HR 1.63, CI: 1.15-2.33), abnormal liver function (HR 1.80, CI: 1.02-3.17), and abnormal renal function (HR 1.58, CI: 1.10-2.27). Mortality rate exhibited a gradual rise as the number of risk factors increased, reaching 46.1% in patients presenting with five or six risk factors. CONCLUSION: One in six patients died within 2 years after LAAO. We identified six independent predictors of mortality. When combined, this model showed a gradual increase in mortality rate with a growing number of risk factors, which may guide appropriate patient selection for LAAO. CLINICAL TRIAL REGISTRATION: The original EWOLUTION registry was registered at clinicaltrials.gov under identifier NCT01972282.