Association of exosomes in patients with compromised myocardial perfusion on functional imaging.

OBJECTIVES: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. METHODS: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. RESULTS: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432-5p and miRNA-382-3p were upregulated in patients with abnormal SSS. CONCLUSIONS: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.

Both HFpEF and HFmrEF should be included in calculating CHA2DS2-VASc score: A Taiwanese longitudinal cohort.

BACKGROUND: Congestive heart failure (CHF) as a risk of stroke in patients with atrial fibrillation (AF) mainly referred to patients with left ventricular systolic dysfunction. Whether this should include patients with preserved ejection fraction is debatable. OBJECTIVE: The study aimed to investigate the variation in stroke risk of AF patients with heart failure with preserved ejection fraction (HFpEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF) for enhancing risk assessment and subsequent management strategies. METHODS: In a longitudinal study using the National Taiwan University Hospital integrated Medical Database, 8358 patients with AF were observed for 10 years (mean follow-up, 3.76 years). The study evaluated the risk of ischemic stroke in patients with differing ejection fractions and CHA2DS2-VASc score, further using Cox models adjusted for risk factors of AF-related stroke. RESULTS: Patients with HFpEF and HFmrEF had a higher mean CHA2DS2-VASc score compared with patients with HFrEF (4.30 ± 1.729 vs 4.15 ± 1.736 vs 3.73 ± 1.712; P < .001) and higher risk of stroke during follow-up (hazard ratio [HR], 1.40 [1.161-1.688; P < .001] for HFmrEF; HR, 1.184 [1.075-1.303; P = .001] for HFpEF vs no CHF) after multivariate adjustment). In patients with lower CHA2DS2-VASc score (0-4), presence of any type of CHF increased ischemic stroke risk (HFrEF HR, 1.568 [1.189-2.068; P = .001]; HFmrEF HR, 1.890 [1.372-2.603; P < .001]; HFpEF HR, 1.800 [1.526-2.123; P < .001] vs no CHF). CONCLUSION: After multivariate adjustment, HFpEF and HFmrEF showed a similar risk of stroke in AF patients. Therefore, it is important to extend the criteria for C in the CHA2DS2-VASc score to include patients with HFpEF and HFmrEF. In patients with fewer concomitant stroke risk factors, the presence of any subtype of CHF increases risk for ischemic stroke.

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.

Pattern of Endothelialization in Left Atrial Appendage Occluder by Optic Coherence Tomography: A Pilot Study.

BACKGROUND: Implantation of the left atrial appendage occluder (LAAO) has been proven to prevent stroke effectively in patients with atrial fibrillation who cannot tolerate anticoagulants. Incomplete endothelization of LAAO may cause device-related thrombus, and currently no good image modality exists to clearly see LAAO endothelialization. We aimed to use coronary optic coherence tomography (OCT) to visualize LAAO endothelialization. METHODS AND RESULTS: We enrolled 14 patients (72.8±9.4 years old) undergoing pulmonary vein isolation with a preexisting LAAO implanted more than 1 year ago (5 Watchman and 9 Amulet). After pulmonary vein isolation, we did OCT via steerable sheath and coronary guiding catheter to adjust OCT probe location and injected contrast medium to visualize the LAAO surface. In vitro testing was also performed to see the bare occluder. In vitro OCT showed the surface of the bare device as an interrupted granule pattern, which included the Watchman surface polytetrafluoroethylene membrane string, Amulet disc metal strut, and inner polytetrafluoroethylene membrane string. In the implanted Watchman, OCT showed endothelialization as a smooth surface layer with noninterrupted coarser granules. In the implanted Amulet, OCT showed endothelialization as thin (early) or thick (late) endothelialization layer covering struts with OCT shadows. Among patients with Watchman, 2 showed no, 2 early, and 1 complete endothelialization. Among patients with Amulet, 2 showed no, 3 early, and 4 late endothelialization. CONCLUSIONS: We demonstrated the feasibility of OCT to visualize LAAO endothelization with high resolution. Further studies are needed to determine antithrombotic regimens if incomplete endothelization is detected. A new OCT catheter may be designed specifically for LAAO.

Use of the CHA2DS2-VASc score to predict subsequent myocardial infarction in atrial fibrillation.

BACKGROUND: The risk of subsequent myocardial infarction (MI) varies widely in patients with atrial fibrillation (AF). No convenient scoring system currently exists to identify MI in AF. While each element of the CHA2DS2-VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke or thromboembolism [doubled]; vascular disease; age 65-75 years; and sex category) score can increase the likelihood of MI, this retrospective longitudinal study aimed to determine the accuracy of the CHA2DS2-VASc score in predicting subsequent MI risk in AF. METHODS: A total of 29,341 patients with AF were enrolled and followed up from January 2010 until the first occurrence of MI or until December 2020. The primary endpoint was the occurrence of subsequent MI. RESULTS: The average age of the study population was 71 years, and 43.2% were male. The mean CHA2DS2-VASc score was found to be higher in patients with AF who had experienced an MI than in those who had not (3.56 ± 1.92 vs. 3.32 ± 1.81, p < 0.001). During the long-term follow-up, the risk of subsequent MI increased by 22% with every one-point increase in the CHA2DS2-VASc score (hazard ratio 1.22, 95% confidence interval 1.19-1.25; p < 0.001). Kaplan-Meier analysis revealed that high CHA2DS2-VASc scores were more likely to experience an MI than those with low CHA2DS2-VASc scores (log-rank p < 0.001). Furthermore, the CHA2DS2-VASc score was a significant predictor of MI in multivariate regression analysis. CONCLUSION: The CHA2DS2-VASc score is a valuable predictor of subsequent MI risk in patients with AF.

Higher Risk of Incident Hyperthyroidism in Patients With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) has been linked to increased hyperthyroidism risk, but contributing factors are unclear. OBJECTIVE: We aimed to investigate whether AF could predict hyperthyroidism and related risk factors. METHODS: This retrospective cohort study was conducted in a tertiary medical institution and included patients aged 18 years or older with AF but without hyperthyroidism at diagnosis. The endpoint was defined as newly diagnosed hyperthyroidism during the follow-up period. RESULTS: The study cohort included 8552 participants. Patients who developed new hyperthyroidism were younger and the proportion of females was higher. They had fewer comorbidities, including diabetes (26% vs 29%, P = .121), hypertension (51% vs 58%, P < .001), coronary artery disease (17% vs 25%, P < .001), stroke (16% vs 22%, P < .001), and end-stage renal disease (ESRD) (6% vs 10%, P = .001). The CHADS2 score was lower in patients with hyperthyroidism (1.74 vs 2.05, P = .031), but there was no statistically significant difference in the CHA2DS2-VASc and HAS-BLED score. Cox regression analysis identified younger age, female gender, history of congestive heart failure, hypertension, diabetes, non-ESRD status, and lower CHADS2 score but not CHA2DS2-VASc as independent predictors of incident hyperthyroidism during follow-up. We also propose a novel, simple risk stratification score (SAD HEC2 score) with excellent predictive power for incident hyperthyroidism during follow-up. CONCLUSION: Our results provide insight into clinical risk factors for the development of hyperthyroidism in AF patients, as identified by the novel SAD HEC2 score. AF appears to be a common precursor of hyperthyroidism.

Sodium-Glucose Cotransporter-2 Inhibitor Prevents Stroke in Patients With Diabetes and Atrial Fibrillation.

Background Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA2DS2-VASc score is a well-established predictor of AF stroke. Patients with AF have an increased risk of stroke if they have diabetes. Use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes. Methods and Results A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016-December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA2DS2-VASc score in the propensity score-matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow-up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA2DS2-VASc score in the propensity score-matched population. The stroke rate was 3.4% (95% CI, 2.8-4.2) patient-years in SGLT2i users and 4.3% (95% CI, 4.0-4.6) in nonusers (P=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 [95% CI, 0.64-0.99]; P=0.043) after adjustment for the CHA2DS2-VASc score. Conclusions Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first-line treatment in patients with diabetes and AF.

Copy number variation of gasdermin D gene is associated with atrial fibrillation-related thromboembolic stroke.

AIMS: Atrial fibrillation (AF) is one of the major causes of ischaemic stroke. In addition to clinical risk evaluated by the CHA2DS2-VASC score, the impact of genetic factors on the risk of AF-related thromboembolic stroke has been largely unknown. We found several copy number variations (CNVs) in novel genes that were associated with thromboembolic stroke risk in our AF patients by genome-wide approach. Among them, the gasdermin D (GSDMD) gene was related to inflammation. We aimed to test whether GSDMD deletion was associated with AF-related stroke. METHODS AND RESULTS: A total of 400 patients with documented non-familial AF were selected, of which 100 patients were diagnosed with ischaemic stroke. The baseline characteristics of age, sex, valvular heart disease, coronary artery disease, heart failure, and CHA2DS2-VASc scores were not statistically different between cases and controls. We found that individuals who carried GSDMD homozygous deletion genotype had a higher risk for ischaemic stroke (odds ratio 2.195; 95% confidence interval, 1.24-3.90; P = 0.007), even adjusted by CHA2DS2-VASc scores. We also validated the association of GSDMD with AF stroke in a large Caucasian population (UK Biobank). CONCLUSION: We found a link between the homozygous deletion of the GSDMD gene and an increased risk of stroke in patients with AF. This may implicate the use of therapy targeting GSDMD in the prevention of ischaemic stroke for AF patients.

CHA2DS2VASc score predicts risk of end stage renal disease in patients with atrial fibrillation: Long-term follow-up study.

Background: End stage renal disease (ESRD) is an increasing worldwide epidemic disease. CHA2DS2-VASc score is a well-established predictor of cardiovascular outcome among atrial fibrillation (AF) patients. Objective: The aim of this study was to test whether CHA2DS2-VASc score is a good predictor for incident ESRD events. Methods: This is a retrospective cohort study (from January 2010 to December 2020) with median follow-up of 61.7 months. Clinical parameters and baseline characteristics were recorded. The endpoint was defined as ESRD with dialysis dependent. Results: The study cohort comprised 29,341 participants. Their median age was 71.0 years, 43.2% were male, 21.5% had diabetes mellitus, 46.1% had hypertension, and mean CHA2DS2-VASc score was 2.89. CHA2DS2-VASc score was incrementally associated with the risk of ESRD status during follow-up. Using the univariate Cox model, we found a 26% increase in ESRD risk with an increase of one point in the CHA2DS2-VASc score (HR 1.26 [1.23-1.29], P < 0.001). And using the multi-variate Cox model adjusted by initial CKD stage, we still observed a 5.9% increase in risk of ESRD with a one-point increase in the CHA2DS2-VASc score (HR 1.059 [1.037-1.082], P < 0.001). The CHA2DS2-VASC score and the initial stage of CKD were associated with the risk of ESRD development in patients with AF. Conclusions: Our results first confirmed the utility of CHA2DS2-VASC score in predicting progression to ESRD in AF patients. The efficiency is best in CKD stage 1.

Impact of pre-existing left atrial appendage occluder on catheter ablation of atrial fibrillation.

BACKGROUND: Patients with drug-refractory atrial fibrillation (AF) and pre-existing left atrial appendage occluder (LAAO) device may need pulmonary vein isolation (PVI). In this pioneer study, we investigated the impact of pre-existing LAAO on AF substrates and outcomes of PVI. METHODS: From our AF registry, 65 drug-refractory patients with LAAO (72.1±11.4 years old; CHA2DS2-VASc score 3.7±2.1) were included for PVI. A balanced control group with 124 patients without LAAO receiving PVI (70.9±10.2 years old, CHA2DS2-VASc 3.6±1.9) were included for comparison. RESULTS: We found PVI is feasible in patients with AF with pre-existing LAAO without new peridevice leak. Two patients with LAAO and one without LAAO had stroke during the procedure (2/65 vs 1/124, p=0.272). Complete isolation of left-sided PVs might not be achieved if the device covered the ridge joining the left atrial (LA) appendage to the body of LA. Local electrogram could be detected over LAAO and there was propagation of conduction over the occluder either under sinus rhythm or under atrial arrhythmia. LAAO might modulate LA substrate and induce peridevice fibrosis, peridevice LA flutter and complex fractionate atrial electrogram. The AF recurrent rate at 1 year was similar between the two groups (9.2% vs 8.8%). CONCLUSIONS: This pioneer study first showed impacts of LAAO on LA substrate and PVI procedure.

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.

Alterations of sympathetic dynamics after atrial fibrillation ablation by analysis sympathetic nerve activity provide prognostic value for recurrence and mechanistic insights into ablation.

Background: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Success is associated with autonomic function modulation; however, the relationship between the changes after ablation is not fully understood. We aimed to investigate the effect of ablation on autonomic modulation by skin sympathetic nerve activity (SKNA) using conventional electrocardiogram (ECG) electrodes and to predict the treatment success. Methods: We enrolled 79 patients. We recorded neuECG for 10 min at 10 kHz before and after ablation. The NeuECG was bandpass-filtered (500-1,000 Hz) and integrated at intervals of 100 ms (iSKNA). iSKNA was averaged over different time windows (1-, 5-,10-s; aSKNAs), and burst analyses were derived from aSKNAs to quantify the dynamics of sympathetic activities. AF recurrence after 3 months was defined as the study endpoint. Results: Sixteen patients experienced AF recurrence after the ablation. For burst analysis of 1-s aSKNA, the recurrence group had a higher bursting frequency than the non-recurrence group (0.074 ± 0.055 vs. 0.109 ± 0.067; p < 0.05) before ablation. The differences between pre- and post-ablation of firing duration longer than 2 s were more in the non-recurrence group (2.75 ± 6.41 vs. -1.41 ± 5.14; p < 0.05), while no significant changes were observed in the percentage of duration longer than 10 s using 5-s aSKNA. In addition, decreases in differences in firing frequency and percentage of both overall firing duration and longer firing duration (> 2 s) between pre- and post-ablation were independently associated with AF recurrence and more area under receiver operating characteristics (ROC) curve in combination with CHADS2 score (0.833). Conclusion: We demonstrated the applicability of neuECG for determining sympathetic modulation during AF ablation. Decreasing sympathetic activity is the key to successful ablation.

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.

Peri-device leakage not CHA2DS2-VASc is associated with post-left atrial appendage closure cardiovascular event.

OBJECTIVE: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, thromboembolic event still occur, and the predictors are unknown. METHODS: The first Asian long-term follow-up study consisted of 308 patients with mean age 71.9±9.5 years, mean CHA2DS2-VASc 4.1 ± 1.8 since 2013. Primary outcome was defined as any type of ischemic stroke/transient ischemic attack (TIA), systemic embolization and cardiovascular death. RESULTS: There was no procedural-related TIA or stroke. After a mean follow-up of 38±16 months, the ischemic stroke/TIA rate was 1.9 and cardiovascular death rate 0.3 per 100 patient-year. The rate of peri-device leak (PDL) was 11.9% and device-related thrombus (DRT) 2.6%. In the multivariable analyses, PDL was the only independent predictor of stroke/TIA (hazard ratio 5.5, p=0.008). CHA2DS2-VASc score, prior history of stroke, DRT and post-procedural anti-thrombotic regimen/duration were not associated with outcomes. Implantation of Watchman was associated with PDL (odds ratio 4.35, p=0.001). CONCLUSIONS: PDL is the only independent predictor of post-LAAO stroke. The risk of stroke for patients with NVAF may be controllable after LAA is occluded, because PDL is preventable and treatable.

Use of nicorandil is associated with increased risk of incident atrial fibrillation.

BACKGROUND: Nicorandil will activate ATP-sensitive potassium channel (KATP). However, activation of potassium channels plays an important role in the mechanism of atrial fibrillation (AF) or atrial flutter (AFL). Whether use of nicorandil might contribute to initiation and/or perpetuation of AF/AFL remained unknown. We determined the relationship between use of nicorandil and risk of atrial fibrillation and determined its molecular mechanism. METHODS: We performed a nested case-control study using a cohort from the National Health Insurance Research Database (NHIRD) of Taiwan. The association between nicorandil use and risk of atrial fibrillation/flutter was estimated by logistic regression model. We also performed molecular, cellular and animal studies to explain the association. RESULTS: A total of 715 individuals who experienced AF/atrial flutter were matched to 72,215 controls. New use of nicorandil was found to be associated with increased risk for AF/AFL (odds ratio [OR], 2.34; 95% CI 1.07-5.13) compared to nitrate use. We found the expression of KATP subunits Kir6.2 and SUR2A in human and rat left atrial tissues. Furthermore, nicorandil directly shortened action potential duration (APD) in rat left atrium and shortened the QT interval of cultured human induced pluripotent stem cell (iPSC) derived cardiomyocytes (iPSC-CMs). CONCLUSIONS: Use of nicorandil was found to be associated with increased risk of AF/AFL. We also showed the expression of KATP subunits in human atria, and a possible mechanism that use of nicorandil increases the risk of AF through activation of KATP and shortening of atrial APD.

An Artificial Intelligence-Enabled ECG Algorithm for the Prediction and Localization of Angiography-Proven Coronary Artery Disease.

(1) Background: The role of using artificial intelligence (AI) with electrocardiograms (ECGs) for the diagnosis of significant coronary artery disease (CAD) is unknown. We first tested the hypothesis that using AI to read ECG could identify significant CAD and determine which vessel was obstructed. (2) Methods: We collected ECG data from a multi-center retrospective cohort with patients of significant CAD documented by invasive coronary angiography and control patients in Taiwan from 1 January 2018 to 31 December 2020. (3) Results: We trained convolutional neural networks (CNN) models to identify patients with significant CAD (>70% stenosis), using the 12,954 ECG from 2303 patients with CAD and 2090 ECG from 1053 patients without CAD. The Marco-average area under the ROC curve (AUC) for detecting CAD was 0.869 for image input CNN model. For detecting individual coronary artery obstruction, the AUC was 0.885 for left anterior descending artery, 0.776 for right coronary artery, and 0.816 for left circumflex artery obstruction, and 1.0 for no coronary artery obstruction. Marco-average AUC increased up to 0.973 if ECG had features of myocardial ischemia. (4) Conclusions: We for the first time show that using the AI-enhanced CNN model to read standard 12-lead ECG permits ECG to serve as a powerful screening tool to identify significant CAD and localize the coronary obstruction. It could be easily implemented in health check-ups with asymptomatic patients and identifying high-risk patients for future coronary events.

Long-term outcomes of percutaneous left atrial appendage closure for the prevention of stroke in patients with atrial fibrillation: Asia-Pacific experience.

BACKGROUND/PURPOSE: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, the long-term outcomes in Asia was generally unknown. METHODS AND RESULTS: This was a retrospective longitudinal study and a total of 124 patients with contraindications to oral anticoagulants or stroke despite under anticoagulants had been enrolled since 2013. Primary efficacy was defined as any type of stroke/systemic embolization and adverse event as any procedure or anti-thrombotic related complications. Twelve patients were excluded due to thrombus in the LAA or oversize LAA. Watchman was successfully implanted in 55 patients (98%) and ACP/Amulet also 55 patients (98%). During follow-up, the ischemic stroke rate was 1.9 in the Watchman and 1.4 per 100 patient-year in the ACP/Amulet group. There were 2 Watchman patients experiencing intracranial hemorrhage. Device-related thrombus (DRT) was noted in 3 patients (2.7%).There was no patient with peri-device lead ≧5 mm. In those patients receiving only local anesthesia, the follow-up echocardiography showed no significant peri-device leak, malposition of LAAO and DRT. CONCLUSION: This long-term follow-up study shows that percutaneous closure of LAA is a safe and technically feasible procedure with satisfactory outcomes in Asia. The procedure success rate, efficacy and adverse event were similar to those reported in the Caucasian populations.