Educational status and the risk of adverse outcomes in Asian patients with atrial fibrillation: a report from the prospective APHRS-AF Registry.

BACKGROUND: The aim of this study was to evaluate the impact of educational status (ES) on the clinical course of Asian patients with atrial fibrillation (AF). METHODS: We used data from the prospective APHRS-AF Registry. ES was classified as follows: low (primary school), medium (secondary), and high (University). The primary outcome was a composite of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Secondary outcomes were each component of the primary outcome, cardiovascular death, and major bleeding. The one-year risk of primary and secondary outcomes was assessed through Cox-regressions. Adherence to the Atrial fibrillation Better Care (ABC) pathway was assessed. RESULTS: Among 2697 AF patients (69±12 years, 34.8% females), 34.6% had low ES; 37.3% had medium ES; and 28.1% had high ES. Compared to patients with medium-high ES, patients with low ES were older, more often females, with a higher prevalence of cardiovascular risk factors, and a lower ABC pathway adherence (30.4% vs. 40.2%, P<0.001). On multivariable analysis, low ES was associated with a higher risk for the primary outcome (HR 1.52,95%CI 1.11-2.06) and all-cause death (HR 1.76,95%CI 1.10-2.83) than medium-high ES. A significant interaction was found for the risk of composite outcome among the different age strata, with the higher risk in the elderly (P for int=0.008), whereas the beneficial effect of the ABC pathway was irrespective of ES (P for int=0.691). CONCLUSIONS: In Asian AF patients, low ES is associated with high mortality. Efforts to improve education and include ES evaluation in the integrated care approach for AF are necessary to reduce the cardiovascular burden in these patients.

Adverse Events and Clinical Correlates in Asian Patients with Atrial Fibrillation and Diabetes Mellitus: A Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Aims. To evaluate the adverse events (and its clinical correlates) in a large prospective cohort of Asian patients with atrial fibrillation (AF) and diabetes mellitus (DM). Material and Methods. We recruited patients with atrial fibrillation (AF) from the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry and included those for whom the diabetic mellitus (DM) status was known. We used Cox-regression analysis to assess the 1-year risk of all-cause death, thromboembolic events, acute coronary syndrome, heart failure and major bleeding. Results. Of 4058 patients (mean age 68.5 ± 11.8 years; 34.4% females) considered for this analysis, 999 (24.6%) had DM (age 71 ± 11 years, 36.4% females). Patients with DM had higher mean CHA2DS2-VASc (2.3 ± 1.6 vs. 4.0 ± 1.5, p < 0.001) and HAS-BLED (1.3 ± 1.0 vs. 1.7 ± 1.1, p < 0.001) risk scores and were less treated with rhythm control strategies compared to patients without DM (18.7% vs. 22.0%). After 1-year of follow-up, patients with DM had higher incidence of all-cause death (4.9% vs. 2.3%, p < 0.001), cardiovascular death (1.3% vs. 0.4%, p = 0.003), and major bleeding (1.8% vs. 0.9%, p = 0.002) compared to those without DM. On Cox regression analysis, adjusted for age, sex, heart failure, coronary and peripheral artery diseases and previous thromboembolic event, DM was independently associated with a higher risk of all-cause death (HR 1.48, 95% CI 1.00-2.19), cardiovascular death (HR 2.33, 95% CI 1.01-5.40), and major bleeding (HR 1.91, 95% 1.01-3.60). On interaction analysis, the impact of DM in determining the risk of all-cause death was greater in young than in older patients (p int = 0.010). Conclusions. Given the high rates of adverse outcomes in these Asian AF patients with DM, efforts to optimize the management approach of these high-risk patients in a holistic or integrated care approach are needed.

Risk of Death and Cardiovascular Events in Asian Patients With Atrial Fibrillation and Chronic Obstructive Pulmonary Disease: A Report From the Prospective APHRS Registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of adverse events in patients with atrial fibrillation (AF); however, few data are available on this topic in Asian populations. METHODS AND RESULTS: Prospective observational study conducted on patients with AF enrolled in the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry. The diagnosis of COPD was based on data reported in the case report form by the investigators. Cox-regression models were used to assess the 1-year risk of a primary composite outcome of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Analysis on single outcomes and cardiovascular death was also performed. Interaction analysis was used to assess the risk of composite outcome and all-cause death in different subgroups. The study included 4094 patients with AF (mean±SD age 68.5±12 years, 34.6% female), of whom 112 (2.7%) had COPD. Patients with COPD showed a higher incidence of the primary composite outcome (25.1% versus 6.3%, P<0.001), all-cause death (14.9% versus 2.6%, P<0.001), cardiovascular death (2.0% versus 0.6%, P<0.001), and heart failure (8.3% versus 6.0%, P<0.001). On multiple Cox-regression analysis, COPD was associated with a higher risk of the primary composite outcome (hazard ratio [HR], 3.17 [95% CI, 2.05-4.90]), all-cause death (HR, 3.59 [95% CI, 2.04-6.30]), and heart failure (HR, 3.32 [95% CI, 1.56-7.03]); no statistically significant differences were found for other outcomes. The association between COPD and mortality was significantly modified by the use of beta blockers (Pint=0.018). CONCLUSIONS: In Asian patients with AF, COPD is associated with worse prognosis. In patients with AF and COPD, the use of beta blockers was associated with a lower mortality. REGISTRATION INFORMATION: clinicaltrials.gov Identifier: NCT04807049.

External Validation of COOL-AF Scores in the Asian Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Background: The COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Levels in Patients with Atrial Fibrillation) risk scores for death, bleeding, and thromboembolic events (TEs) were derived from the COOL-AF cohort from Thailand and require external validation. Objectives: The authors sought to externally validate the COOL-AF scores in the APHRS (Asia-Pacific Heart Rhythm Society) registry and to compare their performance in the ESC-EHRA (European Society of Cardiology-European Heart Rhythm Association) EORP-AF (EURObservational Research Programme in Atrial Fibrillation) General Long-Term Registry. Methods: We studied 3,628 APHRS and 8,825 EORP-AF patients. Receiver operating characteristic (ROC) curves and Cox regression analyses were used to test the predictive value of COOL-AF scores and to compared them with the CHA2DS2-VASc and HAS-BLED scores. Results: Patients in the EORP-AF were older, had a higher prevalence of male sex, and were at higher thromboembolic and hemorrhagic risk than APHRS patients. After 1 year of follow-up in APHRS and EORP-AF, the following events were recorded: 87 (2.4%) and 435 (4.9%) death for any causes, 37 (1.0%) and 111 (1.3%) major bleeding, and 25 (0.7%) and 109 (1.2%) TEs, respectively. In APHRS, the COOL-AF scores showed moderate-to-good predictive value for all-cause mortality (area under the curve [AUC]: 0.77; 95% CI: 0.71-0.83), major bleeding (AUC: 0.68; 95% CI: 0.60-0.76), and TEs (AUC: 0.61; 95% CI: 0.51-0.71), and were similar to the CHA2DS2-VASc and HAS-BLED scores. In EORP-AF, the predictive value of COOL-AF for all-cause mortality (AUC: 0.68; 95% CI: 0.65-0.70) and major bleeding (AUC: 0.61; 95% CI: 0.60-0.62) was modest and lower than in APHRS. In EORP-AF, the COOL-AF score for TE was inferior to the CHA2DS2-VASc score. Conclusions: The COOL-AF risk scores may be an easy tool to identify Asian patients with AF at risk for death and major bleeding and performs better in Asian than in European patients with AF. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia [AF-Registry]; NCT04807049).

Sex-related differences in presentation, treatment, and outcomes of Asian patients with atrial fibrillation: a report from the prospective APHRS-AF Registry.

We aimed to investigate the sex-related differences in the clinical course of patients with Atrial Fibrillation (AF) enrolled in the Asia-Pacific-Heart-Rhythm-Society Registry. Logistic regression was utilized to investigate the relationship between sex and oral anticoagulant, rhythm control strategies and the 1-year chance to maintain sinus rhythm. Cox-regression was utilized to assess the 1-year risk of all-cause, and cardiovascular death, thromboembolic events, acute coronary syndrome, heart failure, and major bleeding. In the whole cohort (4121 patients, 69 ± 12 years,34.3% female), females had different cardiovascular risk factors, clinical manifestations, and disease perceptions than men, with more advanced age (72 ± 11 vs 67 ± 12 years, p < 0.001) and dyslipidemia (36.7% vs 41.7%, p = 0.002). Coronary artery disease was more prevalent in males (21.1% vs 16.1%, p < 0.001) as well as the use of antiplatelet drugs. Females had a higher use of oral anticoagulant (84.9% vs 81.3%, p = 0.004) but this difference was non-significant after adjustment for confounders. On multivariable analyses, females were less often treated with rhythm control strategies (Odds Ratio [OR] 0.44,95% Confidence Interval [CI] 0.38-0.51) and were less likely to maintain sinus rhythm (OR 0.27, 95% CI 0.22-0.34) compared to males. Cox-regressions analysis showed no sex-related differences for the risk of death, cardiovascular, and bleeding. The clinical management of Asian AF patients should consider several sex-related differences.

Early experiences with edoxaban for stroke prevention in atrial fibrillation in the Southeast Asia region.

Edoxaban, a once-daily, direct-acting oral anticoagulant, is approved to prevent stroke or systemic embolism in non-valvular atrial fibrillation (NVAF) and treat venous thromboembolism. The clinical benefit of edoxaban for stroke prevention in Asian patients with NVAF has been demonstrated in clinical and real-world studies. We share early clinical experiences with once-daily edoxaban and discuss its evidence-based use in patients with NVAF in Southeast Asia through several cases of patients at high risk, including frail patients, elderly patients with multiple comorbidities and patients with increased bleeding risk. These cases demonstrate the effectiveness and safety of once-daily edoxaban in patients with NVAF in Southeast Asia.

Integrated Care for Atrial Fibrillation Using the ABC Pathway in the Prospective APHRS-AF Registry.

Background: The Atrial Fibrillation Better Care (ABC) has been proposed as an integrated approach to improve management in patients with atrial fibrillation (AF), based on 3 pillars: "A" Avoid stroke with Anticoagulation; "B" Better symptoms control; "C" Cardiovascular risk-factor and comorbidities management. Objectives: This study sought to investigate the association with outcomes of ABC adherence in the prospective multinational Asia-Pacific Heart Rhythm Society (APHRS) Atrial Fibrillation registry. Method: Cox-regression analyses adjusted for age, sex, CHA2DS2-VASc score, paroxysmal AF, chronic obstructive pulmonary disease, chronic kidney disease, cancer, dyslipidemia, and dementia were performed to investigate the association with outcomes. Primary outcome was a composite of all-cause death, any thromboembolic events, acute coronary syndrome or percutaneous interventional procedures, and advancing heart failure. Results: Of the 4,013 included patients with AF (mean age 68 ± 12 years; 34.4% female); 38.6% were adherent to all 3 main ABC pillars. After 1 year of follow-up, adherence to the ABC pathway was associated with a low incidence of composite outcome (4.0% vs 8.5%, P < 0.001), all-cause and cardiovascular death, and advancing heart failure. On Cox regression analysis, ABC adherence was associated with a lower risk of primary outcome (HR: 0.72; 95% CI: 0.53-0.97), with risk reduction progressively higher with a higher number of ABC criteria attained. No significant interaction in the association was seen according to the different geographic areas (Pint = 0.217). Conclusions: In a large contemporary cohort of Asian patients with AF, adherence to ABC pathway was associated with a reduction of the risk for adverse outcomes. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia (AF-Registry; NCT04807049).

Clinical utility and prognostic implications of the 4S-AF scheme: Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

BACKGROUND: The 4S-AF classification scheme comprises of four domains (stroke risk [St], symptoms [Sy], severity of atrial fibrillation (AF) burden [Sb] and substrate [Su]), which has been recommended in the 2020 ESC guidelines to characterize and evaluate patients with AF. OBJECTIVES: We aimed to determine whether the 4S-AF scheme would be useful for AF characterization and provides prognostic information in a large contemporary prospective Asian registry conducted by the Asia Pacific Heart Rhythm Society (APHRS). METHODS: Among 4666 patients enrolled in APHRS registry, 3586 of them whose data about left atrial (LA) dimension and European Heart Rhythm Association (EHRA) symptom score were available have constituted as the study population. The 4S-AF score was calculated as the sum of each domain with a maximum score of 9. The clinical endpoint was defined as the 1-year composite risk of any thromboembolic event, ischaemic stroke, heart failure, acute coronary syndrome, significant coronary artery disease requiring coronary intervention and all-cause mortality. RESULTS: Based on the 4S-AF domains, 86.7% were 'non-low risk' for stroke; 94.3% had EHRA Class I-II, 48.5% were newly diagnosed or paroxysmal AF; and only 8.4% had no cardiovascular risk factors or LA enlargement. The risk of clinical events was higher in patients who were 'non-low risk' for stroke (aOR 2.175, 95% CI 1.060-4.461), with permanent AF (aOR 1.579, 95% CI 1.106-2.225) and increasing points for substrate (aORs 2.376-4.968 from score 2 to 4). When compared to the first tertile of 4S-AF score (0-3 points), patients in the second tertile (4-5 points) had approximately 2.5-fold increase in adverse events (OR 2.478, 95% CI 1.678-3.661, p < .001), while those in the third tertile (6-9 points), had a 3.5-fold increase (OR 3.484, 95% CI 2.322-5.226, p < .001), both without significant differences between the 5 participating countries (p for interaction > .05). If all 4S-AF domains were appropriately treated, this was associated with a lower risk of composite clinical outcomes (aOR 0.384, p < .001; p for interaction for different countries = .234). CONCLUSIONS: Categorization according to the 4S-AF scheme can be related to the risk of the composite adverse event rate in Asian AF patients, and appropriate treatments based on the 4S-AF scheme resulted in better clinical outcomes. These observations support the characterization and management according to the 4S-AF scheme in Asian patients.

Prognosis and treatment of atrial fibrillation in Asian cities: 1-year review of the Asia-Pacific Heart Rhythm Society Atrial Fibrillation Registry.

AIMS: The aim of this study is to describe the implementation of the current guidance for stroke prevention and treatment option in atrial fibrillation (AF) and to evaluate mortality and morbidity in relation to therapeutic decisions, including persistence with treatment at 1 year in Asia-Pacific regions. METHODS AND RESULTS: We recruited 4664 patients consecutive in- and outpatients with AF who presented to cardiologists in five countries under the Asia-Pacific Heart Rhythm Society (APHRS) in whom 1-year follow-up was completed for 4003 (65.5% male; mean age 68.5 years). Oral anticoagulant (OAC) use remained high, 77% at follow-up, including 17% prescribed a vitamin K antagonist (VKA) and 60% a non-VKA oral anticoagulant (NOAC). At 1-year follow-up, 93% and 88% remained on a VKA or NOAC, respectively. With good adherence to OAC therapy, 1-year mortality was only 2.7%. Most deaths were non-cardiovascular (72.3%) and the 1-year incidence of stroke/transient ischaemic events (TIA) was low (<1%). Hospital readmissions were common for non-cardiovascular cases and atrial tachyarrhythmias. On multivariate analysis, independent baseline predictors of mortality and/or stroke/TIA/peripheral embolism were age, previous heart failure for >12 months, and malignancy. Independent predictors of mortality were age, chronic obstructive pulmonary disease, malignancy, and diuretic use. AF as a primary presentation was predictive of lower mortality and/or stroke/TIA/peripheral embolism as well as mortality. CONCLUSION: In this 1-year analysis of the APHRS-AF registry, overall OAC use and persistence were high and were associated with low 1-year cardiovascular mortality and morbidity, but mortality and morbidity related to non-cardiovascular causes were high in AF patients, particularly from malignancy and pneumonia.

Outcomes of supraventricular tachycardia ablation: Results from the Singapore ablation and cardiac devices registry.

BACKGROUND: The Singapore Cardiac Databank was designed to monitor the performance and outcomes of catheter ablation. We investigated the outcomes of paroxysmal supraventricular tachycardia (PSVT)-ablation in a prospective, nationwide, cohort study. METHODS: Atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entry tachycardia (AVRT), or atrial tachycardia (AT)-ablations in Singapore from 2010 to 2018 were studied. Outcomes include acute success, periprocedural-complications, postoperative pacing requirement, arrhythmic recurrence and 1-year all-cause mortality. RESULTS: Among 2260 patients (mean age 45 ± 18 years, 50% female, 57% AVNRT, 37% AVRT, 6% AT), overall acute success rates of PSVT-ablation was 98.4% and increased in order of AT, AVRT, and AVNRT (p < .001). Periprocedural cardiac tamponade occurred in two AVRT patients. A total of 15 pacemakers (6 within first 30-days, 9 after 30-days) were implanted (seven AV block, eight sinus node dysfunction [SND]), with the highest incidence of pacemaker implantation after AT-ablation (5% vs. 0.6% AVNRT vs. 0.1% AVRT, p < .001). Repeat ablations (0.9% AVNRT, 7% AVRT, 4% AT, p < .001) were performed in 78 (3.5%) patients and 13 (0.6%) patients died within a year of ablation. Among outcomes considered adjusting for age, sex, PSVT-type and procedure-time, AT was independently associated with 6-fold increased odds of total (adjusted odds ratio [AOR] 6.32, 95% confidence interval [CI] 1.95-20.53) and late (AOR 6.38, 95% CI 1.39-29.29) pacemaker implantation, while AVRT was associated with higher arrhythmic recurrence with repeat ablations (AOR 4.72, 95% CI 2.36-9.44) compared to AVNRT. CONCLUSIONS: Contemporary PSVT ablation is safe with high acute success rates. Long-term outcomes differed by nature of the PSVT.

Simultaneous leadless pacemaker and subcutaneous implantable cardioverter-defibrillator implantation-When vascular options have run out.

An end-stage renal failure patient who was planned for a left brachioaxillary arteriovenous graft required an implantable cardioverter-defibrillator for secondary prevention of ventricular tachycardia and a pacemaker for complete heart block but was found to have a right subclavian venous occlusion. Due to the lack of vascular access, we performed a successful subcutaneous implantable cardioverter-defibrillator (S-ICD) and leadless pacemaker implantation. There was no interaction between the devices at the time of implantation, during defibrillation testing and following an appropriate defibrillation therapy.

A novel three base-pair deletion in domain two of the cardiac sodium channel causes Brugada syndrome.

INTRODUCTION: Mutations within SCN5A are found in a significant proportion (15-30%) of Brugada syndrome (BrS) cases and impair sodium transport across excitable cardiac cells that mediate ventricular contractions. Genetic testing offers a means to clinically assess and manage affected individuals and their family members. METHODS AND RESULTS: The proband at age 44 years old exhibited a syncopal event during exercise, and presented later with a spontaneous type-I BrS pattern on 12­lead resting electrocardiogram (ECG). Mutational analysis performed across all SCN5A exons revealed a unique three base-pair deletion p.M741_T742delinsI (c.2223_2225delGAC), in a heterozygous state in the proband and 2 siblings. This mutation was not seen in a cohort of 105 ethnicity-matched controls or in public genome databases. Patch clamp electrophysiology study conducted in TSA201 cells showed an abolishment of sodium current (INa). The proband, and several relatives, also harboured a known SCN5A variant, p.R1193Q (c.3578G>A). CONCLUSION: Our study has demonstrated the deleterious effect of a novel SCN5A mutation p.M741_T742delinsI (c.2223_2225delGAC). The findings highlight the complex effects of gender and age in phenotype manifestation. It also offers insights into improving the long-term management of BrS, and the utility of cascade genetic screening for risk stratification.

Identification of an INa-dependent and Ito-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient.

Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS.

Epicardial ablation utilizing remote magnetic navigation in a patient with Brugada syndrome and inferior early repolarization.

We report a case of epicardial ablation in a combined Brugada and inferior early repolarization syndrome patient with recurrent defibrillator therapy for spontaneous ventricular fibrillation. Electroanatomic mapping and ablation were achieved with remote magnetic navigation. Highly fractionated electrograms were seen epicardially in the anterior right ventricular outflow tract (RVOT) and at the anterior-inferior right ventricle. Ablation of the RVOT region resulted in resolution Brugada pattern electrocardiogram. The inferior early repolarization persisted despite ablation of the inferior right ventricular epicardium. Our patient remained event free at 12-months follow-up.

Remote magnetic catheter navigation versus conventional ablation in atrial fibrillation ablation: Fluoroscopy reduction.

BACKGROUND: Percutaneous transcatheter radiofrequency ablation of atrial fibrillation with remote controlled magnetic navigation (RMN) has been shown to reduce radiation exposure to patients and physicians compared with conventional manual (MAN) ablation techniques. METHODS: Catheter ablation for atrial fibrillation was performed utilizing RMN in 214 consecutive patients and MAN ablation techniques in 229 patients. We compared the fluoroscopy and procedural times between RMN and MAN catheter ablation of atrial fibrillation. Secondary objectives included comparing acute procedural success and short-term complication rates between both ablation strategies. RESULTS: Fluoroscopy time was significantly shorter in the RMN group than the MAN group (53.5±30.1 vs 68.1±27.6 min, respectively; p<0.01); however, the total procedural time was longer in the RMN group (280.2±74.4 min vs 213.1±64.75, respectively; p>0.001). Further subgroup analysis of the most recent 50 ablations each from the RMN and MAN groups, to attenuate the RMN learning curve effect, showed an even greater difference in fluoroscopy time (RMN vs MAN: 53.5±30.1 vs 68.1±27.6 min), though a consistently longer procedure time with RMN (249.5±65.5 vs 186.3±65.6 min, respectively). The acute procedural success rate was comparable between the groups (98.6% vs 95.6%, respectively; p=0.07). The rates of acute complications were similar in both groups (2.3% vs 4.8%, respectively; p=0.16). CONCLUSIONS: In radiofrequency ablation of atrial fibrillation, RMN appears to significantly reduce fluoroscopy time compared with conventional MAN ablation, though at a cost of increased total procedural time, with comparable acute success rates and safety profile. A reduction in procedure and fluoroscopy times is possible with gaining experience.