Long-term outcomes of left atrial appendage occlusion in patients with atrial fibrillation and end stage renal disease.

OBJECTIVE: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia. METHODS: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death. RESULTS: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4-18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1-39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6-17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047). CONCLUSION: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD.

Safety and efficacy of early varenicline prescription in hospitalized patients with acute myocardial infarction: East Asian population.

BACKGROUND: Smoking is a strong risk factor for patients with acute myocardial infarction (AMI). Varenicline is commonly used as a smoking cessation medication, but little is known about its usage in patients with AMI, particularly in hospitalized patients. METHODS: This is a prospective observational, single-center study collected from May 2018 to July 2021. Study patients underwent percutaneous coronary intervention for AMI. The primary end point was set as safety of varenicline, focusing on any serious adverse cardiac events within 24 weeks after treatment. Efficacy of smoking abstinence was also assessed through self-reports of complete abstinence over a week before the 24- week clinic visit. RESULTS: A total of 162 patients hospitalized with AMI were enrolled in our study. Mean age was 56.7 ± 9.95 years and 97% of the patients were male. Most patients (93.2%) received their first dose of varenicline during hospitalization. Time from admission to first dose of study medication was 2.31 ± 2.73 days and duration of drug intake was 7.41 ± 5.18 weeks. At week 24, only one patient had recurrent myocardial infarction, five patients had undergone revascularization for target lesion failure, and no additional patients developed stroke or died. In terms of efficacy, the rate of smoking abstinence was 79%. Light smokers found it easier to quit smoking than heavy smokers. CONCLUSION: This study may represent the first report on the safety and efficacy of early initiation of varenicline treatment in East Asian population hospitalized due to AMI who recently underwent percutaneous coronary intervention.

Dunaliella salina Alga Protects against Myocardial Ischemia/Reperfusion Injury by Attenuating TLR4 Signaling.

Myocardial ischemia/reperfusion (I/R) injury is marked by rapid increase in inflammation and not only results in myocardial apoptosis but also compromises the myocardial function. Dunaliella salina (D. salina), a halophilic unicellular microalga, has been used as a provitamin A carotenoid supplement and color additive. Several studies have reported that D. salina extract could attenuate lipopolysaccharides-induced inflammatory effects and regulate the virus-induced inflammatory response in macrophages. However, the effects of D. salina on myocardial I/R injury remain unknown. Therefore, we aimed to investigate the cardioprotection of D. salina extract in rats subjected to myocardial I/R injury that was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion. Compared with the vehicle group, the myocardial infarct size significantly decreased in rats that were pre-treated with D. salina. D. salina significantly attenuated the expressions of TLR4, COX-2 and the activity of STAT1, JAK2, IκB, NF-κB. Furthermore, D. salina significantly inhibited the activation of caspase-3 and the levels of Beclin-1, p62, LC3-I/II. This study is the first to report that the cardioprotective effects of D. salina may mediate anti-inflammatory and anti-apoptotic activities and decrease autophagy through the TLR4-mediated signaling pathway to antagonize myocardial I/R injury.

Bailout left atrial appendage occluder for pulmonary vein isolation and electrical cardioversion in patients with atrial fibrillation and left atrial appendage thrombus: a pilot study.

BACKGROUND: Cardioversion and catheter-based circumferential pulmonary vein isolation (CPVI) are established rhythm control treatment strategies for patients with atrial fibrillation (AF). However, these treatments are contraindicated for AF patients with a left atrial appendage (LAA) thrombus. METHODS: We conducted the first-in-man case series study to evaluate the feasibility and safety of performing cardioversion or CPVI in AF patients with LAA thrombus immediately after implantation of LAA Occluder (LAAO) in a combined procedure. In our multi-center LAAO registry of 310 patients, 27 symptomatic and drug-refractory AF patients underwent a combined procedure of LAAO and CPVI, among whom 10 (mean age 68 ± 16 years, 6 men) having anticoagulant-resistant LAA thrombus received a bailout procedure of LAAO implantation first then CPVI, and the other 17 patients without LAA thrombus received CPVI first then LAAO for comparison. RESULTS: The mean CHA2DS2-VASc score and HAS-BLED score were comparable between these two groups. In patients with LAA thrombus, we put carotid filters and did a no-touch technique, neither advancing the wire and sheath into the LAA nor performing LAA angiography. After LAAO implantation, the connecting cable was still connected to the occluder when cardioversion was performed. During CPVI, the occluder location was registered in the LA geometry by three-dimensional mapping to guide the catheter not to touch the LAAO. The procedure was successful in all the patients without intra-procedural complications. After a mean follow-up of 1.7 ± 0.7 years, there was no device embolization, peri-device leak ≧ 5 mm or stroke event in both groups. The AF recurrence rate was also similar between the two groups (P = 0.697). CONCLUSION: We demonstrated that cardioversion or CPVI is doable in symptomatic AF patients with LAA thrombus if LAA was occluded ahead as a bailout procedure.

An artificial intelligence-enabled ECG algorithm for identifying ventricular premature contraction during sinus rhythm.

BACKGROUND: Ventricular premature complex (VPC) is a common arrhythmia in clinical practice. VPC could trigger ventricular tachycardia/fibrillation or VPC-induced cardiomyopathy in susceptible patients. Existing screening methods require prolonged monitoring and are limited by cost and low yield when the frequency of VPC is low. Twelve-lead electrocardiogram (ECG) is low cost and widely used. We aimed to identify patients with VPC during normal sinus rhythm (NSR) using artificial intelligence (AI) and machine learning-based ECG reading. METHODS: We developed AI-enabled ECG algorithm using a convolutional neural network (CNN) to detect the ECG signature of VPC presented during NSR using standard 12-lead ECGs. A total of 2515 ECG records from 398 patients with VPC were collected. Among them, only ECG records of NSR without VPC (1617 ECG records) were parsed. RESULTS: A total of 753 normal ECG records from 387 patients under NSR were used for comparison. Both image and time-series datasets were parsed for the training process by the CNN models. The computer architectures were optimized to select the best model for the training process. Both the single-input image model (InceptionV3, accuracy: 0.895, 95% confidence interval [CI] 0.683-0.937) and multi-input time-series model (ResNet50V2, accuracy: 0.880, 95% CI 0.646-0.943) yielded satisfactory results for VPC prediction, both of which were better than the single-input time-series model (ResNet50V2, accuracy: 0.840, 95% CI 0.629-0.952). CONCLUSIONS: AI-enabled ECG acquired during NSR permits rapid identification at point of care of individuals with VPC and has the potential to predict VPC episodes automatically rather than traditional long-time monitoring.

First-in-Human Experience of Using a Universal Steerable Sheath in Implanting Left Atrial Appendage Closure Devices.

Left atrial appendage (LAA) closure (LAAC) device implantation may be challenging in cases with difficult LAA anatomy. A deflectable sheath to approach multiple LAA positions may be helpful. We used a deflectable sheath to implant LAAC devices in 20 patients and included 60 cases using the standard sheaths for comparison. The procedures were successful in all patients without peri-procedural complications. After a median follow-up of 1.52 (IQR: 0.76-2.33) years, none of the patients in the deflectable sheath group had peri-device leak ≥3 mm and experienced thromboembolic stroke. In the standard sheath group, after follow-up of 2.03 (IQR: 0.87-3.19) years, 2 had peri-device leak ≥3 mm and 1 experienced thromboembolic stroke. We first proved the idea of using a universal steerable sheath for LAAC device implantation in difficult LAA anatomy, which also allows rapid switching of different LAAC devices.

Lumbrokinase regulates endoplasmic reticulum stress to improve neurological deficits in ischemic stroke.

Ischemic stroke is characterized by the loss of cerebral blood flow, which frequently leads to neurological deficits. Tissue plasminogen activator is the only therapeutic agent approved to treat ischemic stroke but increases the risk of intracranial hemorrhage and mortality. The fibrinogen-depleting agent lumbrokinase has been used to improve myocardial perfusion in symptomatic stable angina and to prevent secondary ischemic stroke. Lumbrokinase is highly fibrin-specific and only active in the presence of fibrin. Therefore, lumbrokinase has a low risk of hemorrhage due to excessive fibrinolysis. In this study, we aimed to clarify the neuroprotection of lumbrokinase in mice subjected to permanent middle cerebral artery occlusion. Lumbrokinase significantly attenuated infarct volume and improved neurological dysfunction. Lumbrokinase dramatically decreased the expressions of the endoplasmic reticulum (ER) transmembrane receptor protein inositol-requiring enzyme-1 (IRE1) and its downstream transcription factor, XBP-1, caspase-12, and NF-κB activity, thereby significantly inhibiting apoptosis and autophagy and decreasing the NLRP3 inflammasome. Our evidence indicates that post-stroke treatment with lumbrokinase protects against ischemic stroke, thereby regulating ER stress through the collective inhibitory effect of the IRE1 signaling pathways to decrease apoptosis, autophagy, and inflammatory responses. We suggest that lumbrokinase is potential as an adjuvant treatment for ischemic stroke.

Diabetes Mellitus and Heart Failure.

The coexistence of diabetes mellitus (DM) and heart failure (HF) is frequent and is associated with a higher risk of hospitalization for HF and all-cause and cardiovascular mortality. It has been estimated that millions of people are affected by HF and DM, and the prevalence of both conditions has increased over time. Concomitant HF and diabetes confer a worse prognosis than each alone; therefore, managing DM care is critical for preventing HF. This article reviews the prevalence of HF and diabetes and the correlated prognosis as well as provides a basic understanding of diabetic cardiomyopathy, including its pathophysiology, focusing on the relationship between DM and HF with a preserved ejection fraction and summarizes the potential aldosterone and the mineralocorticoid receptor antagonists approaches for managing heart failure and DM. Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) are an emerging class of glucose-lowering drugs, and the role of SGLT2Is in DM patients with HF was reviewed to establish updated and comprehensive concepts for improving optimal medical care in clinical practice.

MicroRNA Let-7a, -7e and -133a Attenuate Hypoxia-Induced Atrial Fibrosis via Targeting Collagen Expression and the JNK Pathway in HL1 Cardiomyocytes.

Fibrosis is a hallmark of atrial structural remodeling. The main aim of this study was to investigate the role of micro-ribonucleic acids (miRNAs) in the modulation of fibrotic molecular mechanisms in response to hypoxic conditions, which may mediate atrial fibrosis. Under a condition of hypoxia induced by a hypoxia chamber, miRNA arrays were used to identify the specific miRNAs associated with the modulation of fibrotic genes. Luciferase assay, real-time polymerase chain reaction, immunofluorescence and Western blotting were used to investigate the effects of miRNAs on the expressions of the fibrotic markers collagen I and III (COL1A, COL3A) and phosphorylation levels of the stress kinase c-Jun N-terminal kinase (JNK) pathway in a cultured HL-1 atrial cardiomyocytes cell line. COL1A and COL3A were found to be the direct regulatory targets of miR-let-7a, miR-let-7e and miR-133a in hypoxic atrial cardiac cells in vitro. The expressions of COL1A and COL3A were influenced by treatment with miRNA mimic and antagomir while hypoxia-induced collagen expression was inhibited by the delivery of miR-133a, miR-let-7a or miR-let-7e. The JNK pathway was critical in the pathogenesis of atrial fibrosis. The JNK inhibitor SP600125 increased miRNA expressions and repressed the fibrotic markers COL1A and COL3A. In conclusion, MiRNA let-7a, miR-let-7e and miR-133a play important roles in hypoxia-related atrial fibrosis by inhibiting collagen expression and post-transcriptional repression by the JNK pathway. These novel findings may lead to the development of new therapeutic strategies.

CHA2DS2-VASc score as an independent outcome predictor in patients hospitalized with acute ischemic stroke.

PURPOSE: Atrial fibrillation (AF) is a significant independent risk factor for 1-year mortality in patients with first acute ischemic stroke (AIS). The CHA2DS2-VASc score was initially developed to assess the risk of stroke in patients with AF. Recently, this scoring system has been demonstrated to have clinical value for predicting long-term clinical outcomes in AIS but the evidence is insufficient. This large-scale prospective cohort study investigated the independent predictive value of the score in such patients. METHODS: We included patients with AIS from the Taiwan Stroke Registry (TSR) during 2006-2016 as the present study population. Patients were divided into those with high (≥2) and low (<2) CHA2DS2-VASc scores. We further analyzed and classified patients according to the presence of AF. The clinical endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year after the index AIS. RESULTS: A total of 62,227 patients with AIS were enrolled. The median age was 70.3 years, and 59% of the patients were women. After confounding factors were controlled, patients with high CHA2DS2-VASc scores had significantly higher incidence of 1-year MACCEs (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.52, 1.76), re-stroke (adjusted HR = 1.28; 95% CI = 1.16, 1.42), and all-cause mortality (adjusted HR = 2.03; 95% CI = 1.83, 2.24) than those with low CHA2DS2-VASc scores did. In the comparison between AF and non-AF groups, the AF group had increased MACCEs (adjusted HR = 1.74; 95% CI = 1.60, 1.89), myocardial infarction (adjusted HR = 4.86; 95% CI = 2.07, 11.4), re-stroke (adjusted HR = 1.47; 95% CI = 1.26, 1.71), and all-cause mortality (adjusted HR = 1.90; 95% CI = 1.72, 2.10). The Kaplan-Meier curve revealed that both CHA2DS2-VASc scores and AF were independent risk predictors for 1-year MACCEs and mortality. CONCLUSIONS: The CHA2DS2-VASc score and AF appeared to consistently predict 1-year MACCEs of AIS patients and provide more accurate risk stratification. Therefore, increased use of the CHA2DS2-VASc score may help improve the holistic clinical assessment of AIS patients with or without AF.

The association between sodium-glucose cotransporter 2 inhibitors and incident dementia: A nationwide population-based longitudinal cohort study.

BACKGROUND: The association of the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor and incident dementia remains unclear. This study aimed to evaluate the risk of incident dementia with the use of SGLT2 inhibitor. METHODS: This is a population-based cohort study utilizing Taiwan's National Health Insurance Research Database. Each patient who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas 1:1 propensity score-matched randomly selected patients who were nonusers of SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was incident dementia. RESULTS: A total of 976,972 patients newly diagnosed with type 2 diabetes mellitus (DM) between 2011 and 2018 were included in this study. After the patients' propensity score matching by age, sex, duration of DM, comorbidities and drug index date of the patients, a total of 103,247 patients in the SGLT2 inhibitor group and 103,247 in the non-SGLT2 inhibitor group were enrolled for analysis. The SGLT2 inhibitor group was associated with a lower risk of incident dementia (adjusted hazard ratio: 0.89, 95% confidence interval: 0.82-0.96; p = .0021). Diabetic complications were significantly lower in the SGLT2 inhibitor group compared with the non-SGLT2 group. Sensitivity analysis was also consistent with the main analysis. CONCLUSIONS: Patients with type 2 DM who were prescribed SGLT2 inhibitors were associated with a lower risk of incident dementia compared with those not prescribed SGLT2 inhibitors in real-world practice.

The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes.

Oxygen pulse (O2P) is a function of stroke volume and cellular oxygen extraction and O2P curve pattern (O2PCP) can provide continuous measurements of O2P. However, measurements of these two components are difficult during incremental maximum exercise. As cardiac function is evaluated using ejection fraction (EF) according to the guidelines and EF can be obtained using first-pass radionuclide ventriculography, the aim of this study was to investigate associations of O2P%predicted and O2PCP with EF in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) and chronic obstructive pulmonary disease (COPD), and also in normal controls. This was a prospective observational cross-sectional study. Correlations of resting left ventricular EF, dynamic right and left ventricular EFs and outcomes with O2P% and O2PCP across the three participant groups were analyzed. A total of 237 male subjects were screened and 90 were enrolled (27 with HFrEF/HFmrEF, 30 with COPD and 33 normal controls). O2P% and the proportions of the three types of O2PCP were similar across the three groups. O2P% reflected dynamic right and left ventricular EFs in the control and HFrEF/HFmrEF groups, but did not reflect resting left ventricular EF in all participants. O2PCP did not reflect resting or dynamic ventricular EFs in any of the subjects. A decrease in O2PCP was significantly related to nonfatal cardiac events in the HFrEF/HFmrEF group (log rank test, p = 0.01), whereas O2P% and O2PCP did not predict severe acute exacerbations of COPD. The findings of this study may clarify the utility of O2P and O2PCP, and may contribute to the currently used interpretation algorithm and the strategy for managing patients, especially those with HFrEF/HFmrEF. (Trial registration number NCT05189301.).

Exposure to Proton Pump Inhibitors and the Risk of Incident Asthma in Patients with Coronary Artery Diseases: A Population-Based Cohort Study.

We aimed to determine the association between proton pump inhibitor (PPI) use and incident asthma in patients with coronary artery disease (CAD). This nationwide cohort study collected claims data from the Taiwanese Bureau of National Health Insurance from 2004 to 2013. The primary outcome, i.e., the risk of incident asthma, was assessed by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). The adjusted HR of asthma development was estimated using the Cox regression model. Sensitivity and subgroup analyses were also conducted. A total of 8894 PPI users and 12,684 H2-receptor antagonist (H2RA) users were included in patients with CAD. Compared with H2RA use, an increased risk of incident asthma was found between PPI use and the risk of incident asthma in patients with CAD after adjusting for sex, age, urbanization, and low income (HR: 1.41; 95% CI: 1.04-1.89). The sensitivity analysis results were consistent with the main analysis results. However, the subgroup analysis revealed no association of incident asthma in patients with diabetes mellitus, hyperlipidemia, stroke, allergic rhinitis, pneumonia, cancer, or depression in the PPI group compared with those in the H2RA group. In conclusion, PPI use increased the risk of asthma development in patients with CAD.