Post-exercise left atrial conduit strain predicted hemodynamic change in heart failure with preserved ejection fraction.

OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: • Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. • Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. • Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.

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.

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.

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.

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.

Prevalence of sudden arrhythmic death syndrome-related genetic mutations in an Asian cohort of whole genome sequence.

AIMS: Recently, the spectrum of background mutation in the genes implicated in sudden arrhythmic death syndrome (SADS), has been elucidated in the Caucasian populations. However, this information is largely unknown in the Asian populations. METHODS AND RESULTS: We assessed the background rare variants (minor allele frequency < 0.01) of major SADS genes in whole genome sequence data of 1514 healthy Taiwanese subjects from the Taiwan Biobank. We found up to 45% of healthy subjects have a rare variant in at least one of the major SADS genes. Around 3.44% of healthy subjects had multiple mutations in one or multiple genes. The background mutation rates in long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy genes were similar, but those in Brugada syndrome (BrS) (SCN5A) and hypertrophic cardiomyopathy (HCM) genes (MYBPC3, MYH7, and TNNT2) were higher, compared to those reported in the Caucasian populations. Furthermore, the rate of incidental pathogenic variant was highest in MYBPC3 gene. Finally, the number of variant was proportional to the exon length of the gene (R2 = 0.486, P = 0.0056) but not related to its functional or evolutionary importance (degree of evolutionary conservation) (R2 = 0.0008, P = 0.9218), suggesting that the mutation was random. The ratio of variant number over exon nucleotide length was highest in MYBPC3, MYH7, and TNNT2 genes. CONCLUSION: Unique features of background SADS gene mutation in the Asian populations include higher prevalence of incidental variant in HCM, BrS, and long QT 3 (SCN5A) genes. HCM genes have the highest variant number per exon length.

Fulminant primary cardiac lymphoma with sudden cardiac death: A case report and brief review.

Primary cardiac lymphoma (PCL) is very rare, with the variable clinical manifestations potentially leading to a delayed diagnosis. PCL is usually detected incidentally through image studies, whereas the diagnosis can be confirmed via analysis of pericardial effusion, endomyocardial biopsy tissue, or surgical specimens. Although no standard therapy has been established for PCL, without treatment, the prognosis is grave, with the estimated overall survival being approximately 1 year. We report a difficult diagnosis and complicated case of fulminant PCL, which is the first comprehensively reported case of PCL with secondary hemophagocytosis. A man presented with progressive dyspnea for 3 weeks, and then sudden cardiac death with ventricular fibrillation occurred. After resuscitation, echocardiography revealed a thickened left ventricular wall and severe mitral regurgitation, and computed tomography showed a right atrial mass with diffuse myocardial lesions. PCL was confirmed through a pathological analysis of specimens collected during mitral valvuloplasty, which also implied extensive myocardial involvement. Bone marrow biopsy demonstrated no evidence of lymphoma involvement, but secondary hemophagocytosis was noted. Despite aggressive chemotherapy, the patient died of sepsis with multiorgan failure 26 days after the operation.

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.

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.

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.

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.

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 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.

The Gut Microbiome, Seleno-Compounds, and Acute Myocardial Infarction.

Background: Gut microbiome alterations might be considered a metabolic disorder. However, the relationship between the microbiome and acute myocardial infarction (AMI) has not been properly validated. Methods: The feces of 44 subjects (AMI: 19; control: 25) were collected for fecal genomic DNA extraction. The variable region V3−V4 of the 16S rRNA gene was sequenced using the Illumina MiSeq platform. The metabolite amounts were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways. Results: The bacteria were more enriched in the AMI group both in the observed operational taxonomic units (OTUs) and faith phylogenetic diversity (PD) (p-value = 0.01 and <0.001 with 95% CI, individually). The Selenomonadales were less enriched in the AMI group at the family, genus, and species levels (all linear discriminant analysis (LDA) scores > 2). Seleno-compounds were more abundant in the AMI group at the family, genus, and species levels (all LDA scores > 2). Conclusions: This is the first study to demonstrate the association of Selenomonadales and seleno-compounds with the occurrence of AMI. Our findings provide an opportunity to identify a novel approach to prevent and treat AMI.

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.

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.

Correlation Between CHA2DS2-VASc Score and Left Atrial Size in Patients With Atrial Fibrillation: A More Than 15-Year Prospective Follow-Up Study.

Background: Left atrial (LA) size represents atrial fibrillation (AF) burden and has been shown to be a predictor for AF stroke. The CHA2DS2-VASc score is also a well-established predictor of AF stroke. It is unknown to cardiologists whether these two risk scores are correlated, whether both are independent prognostic predictors and complimentary to each other, or whether one of them is a major determinant of stroke risk for AF patients. Method: A total of 708 patients from the National Taiwan University Atrial Fibrillation Registry were longitudinally followed up for more than 15 years. Left atrial size was measured by M mode of echocardiography. Adverse thromboembolic endpoints during follow-up were defined as ischemic stroke or transient ischemic attack. Results: The mean age was 72.1 ± 12.9 years, with 53% men. Both LA size and CHA2DS2-VASc score were associated with the risk of stroke in univariate analyses. There was a weak but significant positive correlation between LA size and CHA2DS2-VASc score (r = 0.17, P < 0.0001). Patients with higher CHA2DS2-VASc scores had a higher mean LA size (P < 0.01 for trend). When combining LA size and CHA2DS2-VASc score in the multivariable Cox model, only CHA2DS2-VASc score remained statistically significant [HR 1.39 (1.20-1.63); P < 0.001]. Conclusion: LA size is not an independent predictor of AF stroke, and calculation of CHA2DS2-VASc score may be an alternative to measurement of echocardiographic LA size when evaluating the risk of stroke for AF patients.