Optimal Dose of Edoxaban for Very Elderly Atrial Fibrillation Patients at High Risk of Bleeding: The LEDIOS Registry.

BACKGROUND AND OBJECTIVES: Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding. METHODS: This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding. RESULTS: A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16-4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98-3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75-3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51-2.50 for stroke). CONCLUSIONS: In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03554837.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Improved intra-atrial conduction delay after successful ablation for atrial fibrillation by scar homogenization in right atrium.

Atrial fibrosis in the right atrium (RA) presenting as a low-voltage zone might be the mechanism of atrial fibrillation (AF) and intra-atrial conduction delay. The impact of scar homogenization in RA on intra-atrial conduction delay is unknown. We describe a patient with paroxysmal AF and significant intra-atrial conduction delay with repetitive atrial flutter, triggered from the lateral free wall in the RA between the significant low-voltage zone and slow conduction area after pulmonary vein isolation. Linear ablation along the trabeculated lateral free wall in the RA to homogenize the scar was successfully performed, and the intra-atrial conduction delay improved ultimately.

Artificial intelligence-enhanced 12-lead electrocardiography for identifying atrial fibrillation during sinus rhythm (AIAFib) trial: protocol for a multicenter retrospective study.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, contributing significantly to morbidity and mortality. In a previous study, we developed a deep neural network for predicting paroxysmal atrial fibrillation (PAF) during sinus rhythm (SR) using digital data from standard 12-lead electrocardiography (ECG). The primary aim of this study is to validate an existing artificial intelligence (AI)-enhanced ECG algorithm for predicting PAF in a multicenter tertiary hospital. The secondary objective is to investigate whether the AI-enhanced ECG is associated with AF-related clinical outcomes. Methods and analysis: We will conduct a retrospective cohort study of more than 50,000 12-lead ECGs from November 1, 2012, to December 31, 2021, at 10 Korean University Hospitals. Data will be collected from patient records, including baseline demographics, comorbidities, laboratory findings, echocardiographic findings, hospitalizations, and related procedural outcomes, such as AF ablation and mortality. De-identification of ECG data through data encryption and anonymization will be conducted and the data will be analyzed using the AI algorithm previously developed for AF prediction. An area under the receiver operating characteristic curve will be created to test and validate the datasets and assess the AI-enabled ECGs acquired during the sinus rhythm to determine whether AF is present. Kaplan-Meier survival functions will be used to estimate the time to hospitalization, AF-related procedure outcomes, and mortality, with log-rank tests to compare patients with low and high risk of AF by AI. Multivariate Cox proportional hazards regression will estimate the effect of AI-enhanced ECG multimorbidity on clinical outcomes after stratifying patients by AF probability by AI. Discussion: This study will advance PAF prediction based on AI-enhanced ECGs. This approach is a novel method for risk stratification and emphasizes shared decision-making for early detection and management of patients with newly diagnosed AF. The results may revolutionize PAF management and unveil the wider potential of AI in predicting and managing cardiovascular diseases. Ethics and dissemination: The study findings will be published in peer-reviewed publications and disseminated at national and international conferences and through social media. This study was approved by the institutional review boards of all participating university hospitals. Data extraction, storage, and management were approved by the data review committees of all institutions. Clinical Trial Registration: [cris.nih.go.kr], identifier (KCT0007881).

Clinical and Genetic Features of Korean Inherited Arrhythmia Probands.

BACKGROUND AND OBJECTIVES: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. METHODS: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. RESULTS: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). CONCLUSIONS: There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Net clinical benefit of oral anticoagulants in Korean atrial fibrillation patients with low to intermediate stroke risk: A report from the Clinical Survey on Stroke Prevention in patients with Atrial Fibrillation (CS-SPAF).

Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. Methods: This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.

Standard-Intensity Versus Low-Intensity Anticoagulation with Warfarin in Asian Patients with Atrial Fibrillation: A Multi-Center, Randomized Controlled Trial.

Anticoagulation with warfarin in Asian patients with atrial fibrillation (AF) often has been decreased as an international normalized ratio (INR) of prothrombin time 1.6-2.6 due to fear of bleeding, although universal criteria recommend an INR of 2.0-3.0. In this randomized, open-label trial, low-intensity anticoagulation (INR 1.6-2.6) was compared with standard-intensity anticoagulation (INR 2.0-3.0) with warfarin. A total 616 patients with AF and at least 1 risk factor for stroke were randomized to low-intensity anticoagulation (n = 308) and standard-intensity anticoagulation (n = 308) groups. The intention-to-treat analysis was performed to determine differences. The baseline characteristics of the two groups were comparable. New-onset stroke occurred in 2 patients (0.44% per year) in the low-intensity group and 5 patients (1.05% per year) in the standard-intensity group (HR 0.42, 95% CI 0.08-2.15). Major bleeding occurred in 4 patients (0.89% per year) in the low-intensity group and 5 patients (1.06% per year) in the standard-intensity group (HR 0.84, 95% CI 0.22-3.11). The rate of the net clinical outcome (composite of stroke, systemic embolism, major bleeding, and death) was 1.33% per year in the low-intensity group compared with 2.12% per year in the standard-intensity group (HR 0.63, 95% CI 0.23-1.72). In Asian patients with AF, clinical outcomes were not different between low-intensity and standard-intensity anticoagulation with warfarin.

Updated risk assessments for sudden cardiac death in hypertrophic cardiomyopathy patients with implantable cardioverter-defibrillator.

Hypertrophic cardiomyopathy (HCM) is a genetic disease associated with a risk of malignant ventricular tachyarrhythmias and sudden cardiac death (SCD). Assessment of the SCD risk is crucial for its clinical management, and there has been considerable interest in developing risk stratification strategies. An implantable cardioverter-defibrillator (ICD) is a life-saving treatment for patients with HCM who are at a high-risk of ventricular tachyarrhythmias and SCD. However, a substantial number of ICD recipients experience adverse effects arising from inappropriate device therapy and implant-related complications. This has led to numerous investigations of the risk of SCD and the indications for ICD implantation. American guidelines were recently updated to include new risk markers, including left ventricular systolic dysfunction, apical aneurysm, and extensive late gadolinium enhancement, while European guidelines recommend individualized estimated 5-year SCD risk assessment models. Studies evaluating other risk factors for SCD in patients with HCM have also been published. Drawing on recent guidelines and publications on clinical risk factors, we focus this review on updated risk assessments for SCD with ICD therapy in patients with HCM.

Validation of Biomarker-Based ABCD Score in Atrial Fibrillation Patients with a Non-Gender CHA2DS2-VASc Score 0-1: A Korean Multi-Center Cohort.

PURPOSE: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0-1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m²), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0-1. MATERIALS AND METHODS: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0-1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. RESULTS: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P-Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11-0.63, p=0.003). CONCLUSION: The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0-1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0-1.

ABO Blood Type Is Associated with Thrombotic Risk in Patients with Nonvalvular Atrial Fibrillation.

Blood type is reportedly correlated with the occurrence of cardiovascular diseases, presumably because of its effect on thrombogenicity. However, the relationship between blood type and thrombotic complications in atrial fibrillation (AF) remains unclear. This retrospective study analyzed the blood types of 1170 AF patients (mean age, 70 years; 58% men) who were followed up for up to 4 years. Patients with greater than mild mitral stenosis or prosthetic valves were excluded. The cohort included 305 (26%) type O, 413 (35%) type A, 333 (28%) type B, and 119 (10%) type AB patients. The primary endpoint of major adverse cerebrovascular events (MACE) occurred in 52 (4.4%) patients. When longitudinal outcomes were plotted, AB blood type patients had worse prognosis than non-AB blood type patients (p = 0.039), particularly type O blood patients (p = 0.049). Multivariate Cox regression analysis revealed that AB blood type was associated with higher MACE rates (adjusted hazard ratio, 2.01; 95% confidence interval, 1.01-4.00; p = 0.048) than non-AB blood types independent of anticoagulation therapy duration or CHA2DS2-VASc score. These indicate that AF patients with AB blood type are at an increased risk of MACE compared to those with non-AB blood type independent of the duration of anticoagulation or the CHA2DS2-VASc score.

Unexpected paced wide QRS complex rhythm after successful implantation of cardiac resynchronization therapy; what is the mechanism?

The adaptive CRT (aCRT) is an innovative algorithm that was developed to avoid unnecessary right ventricular (RV) pacing through continuous intracardiac delay evaluation. We present a case of unexpected wide QRS paced rhythm after successful implantation of CRT in patients with right bundle branch block (RBBB) and describe the reasons and the programming changes required to resolve it.

The Thromboembolic Predictability of CHA2DS2-VASc Scores Using Different Echocardiographic Criteria for Congestive Heart Failure in Korean Patients with Nonvalvular Atrial Fibrillation.

The association between congestive heart failure (CHF) of the CHA2DS2-VASc scores and thromboembolic (TE) events in patients with atrial fibrillation (AF) is a topic of debate due to conflicting results. As the importance of diastolic impairment in the occurrence of TE events is increasingly recognized, it is crucial to evaluate the predictive power of CHA2DS2-VASc scores with C criterion integrating diastolic parameters. We analyzed 4200 Korean nonvalvular AF patients (71 years of age, 59% men) to compare multiple echocardiographic definitions of CHF. Various guideline-suggested echocardiographic parameters for systolic or diastolic impairment, including left ventricular ejection fraction (LVEF) ≤ 40%, the ratio of early diastolic mitral inflow velocity to early diastolic velocity of the mitral annulus (E/E') ≥ 11, left atrial volume index > 34 mL/m2, and many others were tested for C criteria. Multivariate-adjusted Cox regression analysis showed that CHA2DS2-VASc score was an independent predictor for composite thromboembolic events only when CHF was defined as E/E' ≥ 11 (hazard ratio, 1.26; p = 0.044) but not with other criteria including the original definition (hazard ratio, 1.10; p = 0.359). Our findings suggest that C criterion defined as diastolic impairment, such as E/E' ≥ 11, may improve the predictive value of CHA2DS2-VASc scores.

Cognitive Function of Recipients of Primary or Secondary Defibrillator Therapy: A Comparative Study Involving Nondefibrillator Patients With Systolic Heart Failure.

BACKGROUND: The extent to which cognitive function differs between patients who receive implantable cardioverter-defibrillator (ICD) therapy and patients with heart failure (HF) who do not receive ICD therapy remains to be elucidated. OBJECTIVES: The aim of this study was to compare the cognitive function between patients with primary or secondary ICDs and patients with HF without an ICD. METHODS: This descriptive, comparative study included 116 patients who received ICDs and 74 patients with HF who did not receive ICDs. Patients underwent neuropsychological assessment for general cognition, memory, and executive function. RESULTS: Immediate recall memory loss (18.9%) occurred more often in patients with HF without an ICD than in patients with primary (3.1%) and secondary (7.1%) ICDs (P = .018). After adjusting for age and education, delayed recall memory of patients with HF without ICDs was significantly worse than that of patients with primary ICDs (4.0 vs 6.5; P < .001), whereas delayed recall memory of patients with primary ICDs was better than that of patients with secondary ICDs (6.0 vs 6.5; P = .006). Executive function of patients with HF without ICDs was significantly worse than that of patients with primary (35 vs 58 seconds; P < .001) and secondary (28 vs 58 seconds; P = .0012) ICDs. CONCLUSIONS: Patients with ICDs, regardless of primary or secondary indication, had less impairment of memory and executive function than patients with HF without ICDs, implying that ICD therapy did not interfere with cognitive performance. Cognitive screening as a part of routine care could be helpful for identifying impairment and implementing early cognitive training, especially in patients with HF.

Ventricular fibrillation and sudden cardiac arrest in apical hypertrophic cardiomyopathy: Two case reports.

BACKGROUND: Apical hypertrophic cardiomyopathy (HCM) is considered to have a benign prognosis in terms of cardiovascular mortality. This serial case report aimed to raise awareness of ventricular fibrillation (VF) and sudden cardiac death (SCD) in apical HCM. CASE SUMMARY: Here we describe two rare cases of apical HCM that presented with documented VF and sudden cardiac collapse. These patients were previously not recommended for primary prevention using implantable cardioverter-defibrillator (ICD) therapy based on current guidelines. However, both received ICD therapy for the secondary prevention of SCD. CONCLUSION: These cases illustrate serious complications including VF and aborted sudden cardiac arrest in apical HCM patients who are initially not candidates for primary prevention using ICD implantation based on current guidelines.

The Effects of Single Nucleotide Polymorphisms in Korean Patients with Early-onset Atrial Fibrillation after Catheter Ablation.

BACKGROUND: This study evaluated the status of single nucleotide polymorphisms (SNPs) in Korean patients with early-onset (< 40 years old) atrial fibrillation (AF) and their effects on the outcome after catheter ablation. METHODS: A total of 89 patients (35.7 ± 3.7 years, 81 males) with drug-refractory AF (paroxysmal 64.0%) who underwent catheter ablation were included in this study. Sixteen SNPs, including rs13376333, rs10465885, rs10033464, rs2200733, rs17042171, rs6843082, rs7193343, rs2106261, rs17570669, rs853445, rs11708996, rs6800541, rs251253, rs3807989, rs11047543, and rs3825214, were genotyped. Serial 48-hour Holter monitoring was conducted to detect AF recurrences during long-term follow up. RESULTS: Wild-type genotypes of rs11047543 (GG; 26/69 [37.7%] vs. GA; 13/18 [72.2%] vs. AA; 0/0 [0%], P = 0.009) and rs7193343 (CC; 0/7 [0%] vs. CT; 22/40 [55.0%] vs. TT; 18/41 [43.9%], P = 0.025) and the homozygous variant of rs3825214 (AA; 16/31 [51.6%] vs. AG; 22/43 [51.2%] vs. GG; 2/13 [15.4%], P = 0.056) were significantly associated with a lower rate of late recurrence. When the patients were assigned to four groups according to the number of risk alleles (n = 0-3), there were significant differences in recurrence rate (n = 0; 0/3 vs. n = 1; 2/13 [15.4%] vs. n = 2; 24/52 [46.2%] vs. n = 3; 13/17 [76.5%], P = 0.003). When correcting for multiple variables, rs11047543 (hazard ratio [HR], 2.723; 95% confidence interval [CI], 1.358-5.461; P = 0.005) and the number of risk alleles (HR, 2.901; 95% CI, 1.612-5.219; P < 0.001) were significantly associated with recurrence of AF after catheter ablation. CONCLUSION: Polymorphisms on rs7193343 closest to ZFHX3 (16q22), rs3825214 near to TBX5 (12q24), and rs11047543 near to SOX5 (12p12) modulate the risk for AF recurrence after catheter ablation. The number of risk alleles of these 3 SNPs was an independent predictor of recurrence during long-term follow up in Korean patients with early-onset AF.

Associations of Advance Directive Knowledge, Attitudes, and Barriers/Benefits With Preferences for Advance Treatment Directives Among Patients With Heart Failure and Their Caregivers.

BACKGROUND: Patients with heart failure (HF) have not been considered as major beneficiaries of advance directives (ADs). We analyzed factors affecting the preferences for the adoption of ADs by patients with HF and their caregivers. METHODS AND RESULTS: Seventy-one patient (mean age: 68 years)-caregiver (mean age: 55 years) dyads were enrolled during clinic visits for routine care at a single institution and completed questionnaires during in-person visits. Cohen's kappa coefficients and generalized estimating equation models were used to analyze the data. The agreement on dyadic perspectives for aggressive treatments was poor or fair, whereas agreement relative to hospice care was moderate (k = 0.42, 95% confidence interval = 0.087-0.754). Both patients and caregivers demonstrated poor knowledge of ADs and similar levels of perceived benefits and barriers to advance care planning. However, the caregivers had more positive attitudes toward ADs than patients. Patients and caregivers who were older and/or males had greater odds of preferring aggressive treatments and/or hospice care. Further, those with depressive symptoms had lower odds of preferring hospice care. CONCLUSION: The dyadic agreement was moderately high only for hospice care preferences. Both patients and caregivers demonstrated knowledge of shortfalls regarding ADs. Timely AD discussions could increase dyadic agreement and enhance informed and shared decision-making regarding medical care.