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.

Reinforcement of a Subcutaneous Pocket for Implantable Cardioverter Defibrillator Insertion Using Acellular Dermal Matrix: A Case Report.

Pediatric patients who undergo implant insertion into the chest wall face a high risk of implant exposure to the external environment. Five months after an 8-year-old boy underwent implantable cardioverter-defibrillator (ICD) implantation in a subcutaneous pocket in the left anterolateral chest wall to manage long QT syndrome, ICD replacement became necessary owing to exposure risk from distal and lateral thinning of the ICD pocket. Pocket rupture and exposure would increase the risk of infection; therefore, we performed ICD removal and primary pocket closure. Two weeks later, a new suprafascial pocket was created, an acellular dermal matrix (ADM) was attached to the inner wall to prevent ICD protrusion, and a new ICD was inserted. One year postoperatively, the ADM was engrafted, and no complications were observed. A thin subcutaneous layer increases the risk of ICD implantation complications. Inner wall strengthening with an ADM can help prevent pocket rupture.

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.

Case Report: Comprehensive evaluation of ECG phenotypes and genotypes in a family with Brugada syndrome carrying SCN5A-R376H.

Background: Brugada syndrome (BrS) is a channelopathy that can lead to sudden cardiac death in the absence of structural heart disease. Patients with BrS can be asymptomatic or present with symptoms secondary to polymorphic ventricular tachycardia or ventricular fibrillation. Even though BrS can exhibit autosomal dominant inheritance, it is not easy to identify the phenotype and genotype in a family thoroughly. Case: We report the case of a 20-year-old man with variants in SCN5A and RyR2 genes who was resuscitated from sudden cardiac death during sleep due to a ventricular fibrillation. The patient did not have underlying diseases. The routine laboratory results, imaging study, coronary angiogram, and echocardiogram (ECG) were normal. A type 1 BrS pattern was identified in one resting ECG. Furthermore, prominent J wave accentuation with PR interval prolongation was identified during therapeutic hypothermia. Therefore, we were easily able to diagnose BrS. For secondary prevention, the patient underwent implantable cardioverter defibrillator implantation. Before discharge, a genetic study was performed using next-generation sequencing. Genotyping was performed in the first-degree relatives, and ECG evaluations of almost all maternal and paternal family members were conducted. The proband and his mother showed SCN5A-R376H and RyR2-D4038Y variants. However, his mother did not show the BrS phenotype on an ECG. One maternal aunt and uncle showed BrS phenotypes. Conclusion: Genetics alone cannotdiagnose BrS. However, genetics could supply evidence or direction for evaluating ECG phenotypes in family groups. This case report shows how family evaluation using ECGs along with a genetic study can be used in BrS diagnosis.

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study.

The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.

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.

Modified application of SAMe-TT2R2 scoring system in Asian patients with atrial fibrillation for the selection of oral anticoagulants.

BACKGROUND/AIMS: The SAMe-TT2R2 score is used for assessing anticoagulation control (AC) quality with warfarin. However, it is hard to apply SAMe-TT2R2 score in Asian patients with atrial fibrillation (AF), because it has not been proven in those populations. This study aimed to validate the SAMe-TT2R2 score in Asian patients with AF and suggest a modified SAMe- TT2R2 score for this population. METHODS: We analyzed 710 Korean patients with AF who were using warfarin. The AC quality was assessed as the mean time in therapeutic range (TTR). Each component of SAMe-TT2R2 score was evaluated for the relationship with AC. Further clinical factors that predict AC were analyzed. Identified factors were re-assorted and constructed as SA2Me-TTR scoring system. RESULTS: Of the components of the SAMe-TT2R2 score, female, age, and rhythm control were associated with AC. Heart failure and renal insufficiency were newly identified factors associated with AC. The modified SA2Me-TTR score was reconstructed with the relevant risk factors (S, female gender, 1 point; A, age < 60 yr, 2 points; Me, medical history of heart failure, 1 point; T, treatment for rhythm control, 1 point; T, history of stroke or transient ischemic attack, 1 point; R, renal insufficiency, 1 point). The modified SA2Me-TTR score demonstrated an excellent relationship with the grading of AC. The modified SA2Me-TTR score ≤ 1 identified patients with good AC (hazard ratio 2.46, 95% CI 1.75-3.47). CONCLUSION: The modified SA2Me-TTR score was useful for guiding oral anticoagulants selection in Asian patients with AF.

Joseph E. Murray's Struggle to Transplant Kidneys: Failure, Individuality, and Plastic Surgery, 1950-1965.

This paper offers a historical analysis of the American plastic surgeon and Nobel laureate Joseph E. Murray's kidney transplantation. After succeeding in the first kidney transplantation between monozygotic twins in 1954, he transplanted kidneys between genetically distinct people after X-radiation and immunosuppressants. Amid these achievements, however, Murray encountered numerous failures, which he thought were closely intertwined with each patient's physiological and pathological individuality. As he appropriated his expertise in plastic surgery for kidney transplantation, this individuality became a major issue that he had to cope with in his efforts to avoid failures. To him, kidney transplantation could fail because of each individual's immunological barrier or constitutional singularity that could engender unexpected complications. Although he could neither explain nor control many of these failures, I argue that his unsuccessful work and patient individuality played multiple roles in shaping his operations as a plastic surgeon. They structured the path of his surgical research, made sense of it, defended him from criticism, and formed the way that he presented the results of his work with an immunological implication. Consequently, Murray, with little scientific training, articulated an important dimension of immunological tolerance relevant to clinical settings.

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.

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.

Low-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

In the last decade, non-vitamin K antagonist oral anticoagulants (NOACs), a new generation of OACs, were introduced to prevent thromboembolism in patients with atrial fibrillation. Although vitamin K-dependent anticoagulants have long been used as OACs, their inherent disadvantage of considerable bleeding complications has limited their use. NOACs demonstrate similar or superior clinical outcomes to those of warfarin. Although strict dose reduction criteria are recommended for NOACs, low-dose NOACs are frequently utilized, especially in Asian patients. Low-dose NOACs have shown clinical outcomes similar to those of warfarin in randomized controlled trials (RCTs) and real-world studies. However, off-label low-dose NOACs have shown inconsistent results compared with standard-dose NOACs and warfarin. Therefore, strict dose reduction criteria for NOACs should be followed until RCTs confirm the issues associated with NOAC underdosing.

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.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Edoxaban treatment in atrial fibrillation in routine clinical care: One-year outcomes of the prospective observational ETNA-AF study in South Korean patients.

Background: The real-world outcomes of edoxaban treatment in patients with atrial fibrillation (AF) were analyzed in the ETNA-AF (Edoxaban Treatment in Routine Clinical Practice) study involving data from multiple regional registries. This report addresses effectiveness and safety of edoxaban in the Korean ETNA-AF population. Methods: One-year data from 1887 Korean ETNA-AF participants were analyzed according to edoxaban dose and patient age and compared with results of other ETNA-AF registries. Results: Approximately 70% of patients received the recommended doses of edoxaban (60 mg/30 mg); non-recommended 60 mg and 30 mg doses were prescribed to 9.6% and 19.8% of the patients, respectively. The proportions of reference age (<65 years), youngest-old (65-74 years) and middle-old/oldest-old (≥75 years) groups were 21.4%, 40.2%, and 38.4%, respectively. Incidence of major or clinically relevant nonmajor bleeding was similar within dose (0.57%-1.71%) and age subgroups (1.26%-1.63%). Incidence of net clinical outcome, a composite of stroke, systemic embolic event, major bleeding, and all-cause mortality, was also comparable among dose subgroups (1.14%-3.10%) and age subgroups (2.28%-2.78%). The percentage of Korean patients receiving non-recommended 30 mg (19.8%) was over twice that of the European population (8.4%). However, the clinical outcomes were generally similar among different populations included in the ETNA-AF study. Conclusions: The outcomes in the Korean ETNA-AF population are like those in the global ETNA-AF population, with overall low event rates of stroke, major bleeding and all-cause mortality across age and dose subgroups. Edoxaban can be used effectively and safely in specific populations of Korean AF patients, including the elderly.

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).

Rhythm Control and Cardiovascular or Cerebrovascular Outcomes in Patients with Atrial Fibrillation: A Study of the CODE-AF Registry.

BACKGROUND: It is not clear whether the data regarding rhythm control during atrial fibrillation (AF) contained in AF registries is prognostically significant. Thus, this study investigated the relationship between rhythm control and cardiovascular outcomes in patients in contemporary AF registries. METHODS: This study was conducted using data from 6670 patients with AF receiving oral anticoagulation in the CODE-AF registry. We used propensity overlap weighting to account for differences in baseline characteristics between the rhythm control and rate control groups. The primary outcome was a composite of the rate of death due to cardiovascular causes, stroke, acute coronary syndrome, and heart failure. The secondary outcomes were individual components of the primary outcome. RESULTS: In the CODE-AF registry, 5407 (81.1%) patients were enrolled three months after AF diagnosis. During a median follow-up period of 973 days (interquartile range: 755-1089 days), a primary outcome event occurred in 72 patients in the rhythm control group (1.4 events per 100 person-years) and in 211 patients in the rate control group (1.8 events per 100 person-years). However, after overlap weighting, the incidence rates were 1.4 and 1.5 events per 100 person-years, respectively. No significant difference was found in either the primary outcome (weighted HR: 0.87; 95% CI: 0.66-1.17; p = 0.363) or secondary outcomes between the rhythm control and rate control groups. CONCLUSION: In a prospective AF registry in which most of the population was enrolled at least three months after AF diagnosis, no difference in the risk of cardiovascular or cerebrovascular outcomes was found between the rhythm control and rate control groups, suggesting the early rhythm control should be considered to improve the outcome of patients.

Antiarrhythmic Effect of Artemisinin in an Ex-vivo Model of Brugada Syndrome Induced by NS5806.

BACKGROUND AND OBJECTIVES: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (Ito) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of Ito channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. METHODS: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 µM), calcium channel blocker verapamil (1 µM), and Ito agonist NS5806 (6-10 µM) were used. Artemisinin (100-150 µM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. RESULTS: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. CONCLUSIONS: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including Ito channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.

The mechanism of premature ventricular complexes (PVC) occurring in the ventricular outflow tract (OT) is related to an intracellular calcium overload and delayed afterdepolarizations that lead to triggered activity. The guidelines recommend using beta-blockers and flecainide for idiopathic PVCs, but they also acknowledge the limited evidence supporting this recommendation. We conducted a multicenter, randomized, open-label pilot study comparing the effect of carvedilol and flecainide on OT PVC, which are widely used to treat this arrhythmia. Patients with a 24 h Holter recording a PVC burden ≥ 5%, which showed positive R waves in leads II, III, and aVF, and without structural heart disease were enrolled. They were randomly assigned to the carvedilol or flecainide group, and the maximum tolerated dose was administered for 12 weeks. A total of 103 participants completed the protocol: 51 with carvedilol and 52 with flecainide. After 12 weeks of treatment, the mean PVC burden significantly decreased in both groups: 20.3 ± 11.5 to 14.6 ± 10.8% with carvedilol (p < 0.0001) and 17.1 ± 9.9 to 6.6 ± 9.9% with flecainide (p < 0.0001). Both carvedilol and flecainide effectively suppressed OT PVCs in patients without structural heart disease, with flecainide showing a superior efficacy compared to carvedilol.

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.