A Rare Noncoding Enhancer Variant in SCN5A Contributes to the High Prevalence of Brugada Syndrome in Thailand.

BACKGROUND: Brugada syndrome (BrS) is a cardiac arrhythmia disorder that causes sudden death in young adults. Rare genetic variants in the SCN5A gene encoding the Nav1.5 sodium channel and common noncoding variants at this locus are robustly associated with the condition. BrS is particularly prevalent in Southeast Asia but the underlying ancestry-specific factors remain largely unknown. METHODS: Genome sequencing of BrS probands and population-matched controls from Thailand was performed to identify rare noncoding variants at the SCN5A-SCN10A locus that were enriched in patients with BrS. A likely causal variant was prioritized by computational methods and introduced into human induced pluripotent stem cell (hiPSC) lines using CRISPR-Cas9. The effect of the variant on SCN5A expression and Nav1.5 sodium channel current was then assessed in hiPSC-derived cardiomyocytes (hiPSC-CMs). RESULTS: A rare noncoding variant in an SCN5A intronic enhancer region was highly enriched in patients with BrS (detected in 3.9% of cases with a case-control odds ratio of 45.2). The variant affects a nucleotide conserved across all mammalian species and predicted to disrupt a Mef2 transcription factor binding site. Heterozygous introduction of the enhancer variant in hiPSC-CMs caused significantly reduced SCN5A expression from the variant-containing allele and a 30% reduction in Nav1.5-mediated sodium current density compared with isogenic controls, confirming its pathogenicity. Patients with the variant had severe phenotypes, with 89% experiencing cardiac arrest. CONCLUSIONS: This is the first example of a functionally validated rare noncoding variant at the SCN5A locus and highlights how genome sequencing in understudied populations can identify novel disease mechanisms. The variant partly explains the increased prevalence of BrS in this region and enables the identification of at-risk variant carriers to reduce the burden of sudden cardiac death in Thailand.

Critical appraisal of technologies to assess electrical activity during atrial fibrillation: a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology.

We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.

Transvenous Lead Extraction (TLE) Procedure: Experience from a Tertiary Care Center in Thailand.

BACKGROUND: Transvenous Lead Extraction (TLE) is a standard treatment for some late Cardiac Implantable Electronics Device (CIED) complications. The outcome of transvenous lead extraction procedure in Thailand is not robust. METHODS: A Single-center retrospective cohort of TLE procedures performed at Ramathibodi hospital between January 2008 and December 2020 was studied. RESULTS: There were 157 leads from 105 patients who underwent lead removal procedure during the specified period. Data analysis was performed from 79 TLE patients due to incomplete data and lead explant procedure of the excluded subjects. Mean patients' age was 57.7 ± 18.7 years, with 70.9% male. There were 82 pacemaker leads, 35 ICD leads, and 5 CS leads (mean number of leads were 1.54 ± 0.66 per patient), with mean implanted duration of 87.8 ± 68.2 months. Main indication for TLE was infection-related, which accounted for 67.1% of the cases. Overall clinical success rate was 97.5%. Mean operative time was 163.8 ± 69.5 min. Major complications occurred in 4 patients (5.1%) with one in-hospital mortality from severe sepsis. CONCLUSION: TLE using laser sheath and rotating mechanical sheath for transvenous lead extraction is effective and safe, even outside high-volume center.

Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial.

BACKGROUND: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. METHODS: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. CONCLUSION: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Worldwide Prevalence of Brugada Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Brugada syndrome (BrS) is considered to be an inherited arrhythmic disease associated with fatal complications and premature sudden unexpected death. The prevalence of the Brugada electrocardiogram pattern (BrP) has been reported in several countries. Nonetheless, the specific worldwide prevalence of BrS has not been reported. OBJECTIVE: We estimated the worldwide prevalence of BrS and Type-2/3 BrP in general adult populations using a systematic review and meta-analysis of the existing literature. METHODS: We thoroughly searched MEDLINE and SCOPUS databases up to March 2017. Included studies were population-based electrocardiogram studies in which prevalence was presented or could be calculated from available data. Pooled prevalence by country/region and/or ethnicity was estimated using a random-effect model. RESULTS: Twenty-eight articles with atotal population of 369,068 were included in this study. The worldwide pooled prevalence of BrS was 0.5 per 1,000 [95% confidence interval (CI): 0.3-0.7]. The highest prevalence was reported in Southeast Asia (1.8 per 1,000, 95% CI: 0.5-6.6); the lowest was found in North Africa (0 per 1,000). BrS in Asians was nine times more common than in Caucasians and 36 times more common than in Hispanics. The worldwide pooled prevalence of Type-2/3 BrP was 6.1 per 1,000 (95% CI: 5.0-7.1). The highest prevalence was also reported in Southeast Asia (35.5 per 1,000, 95% CI: 17.1-53.9). CONCLUSIONS: This study revealed a significant difference in the worldwide prevalence of BrS and Type-2/3 BrP. Brugada electrocardiogram patterns are highly prevalent in Southeast Asia.

Clinical safety and performance of a MRI conditional pacing system in patients undergoing cardiac MRI.

BACKGROUND: Utilization of cardiac magnetic resonance imaging (cMRI) as an imaging modality in clinical practice is rapidly increasing. More evidence from randomized studies establishing clinical safety and performance of pacing systems in patients undergoing a cMRI scan is needed. OBJECTIVES: The purpose of this prospective, multicenter, randomized study was to demonstrate safety and efficacy of the Accent MRI™ conditional pacing systems (St. Jude Medical, St. Paul, MN, USA) in patients undergoing cMRI scan. METHODS: Patients (n  =  283) indicated for dual-chamber pacemaker implant were randomized to either the MRI Group (MG) (n  =  140) or the Control Group (CG) (n  =  143) after successful device implantation of the Accent MRI™ system. Clinical evaluation and device interrogation were performed at pre- and post-MRI scan, and 1 month post-MRI for all patients. At 9-12 weeks postimplant, patients in MG underwent a nondiagnostic cMRI scan at 1.5 Tesla (T), while patients in CG underwent device interrogation and clinical evaluation twice with a 45-minute waiting period in between. The safety endpoint was freedom from MRI scan-related complications and that for efficacy was significant changes in right atrial/ventricular capture threshold and sensing amplitude between right before MRI, immediately after MRI, and 1 month post-MRI. RESULTS: Results showed 100% freedom from MRI scan-related complications. There were no significant changes in device performance between pre-MRI scan and 1 month post-MRI scan time points in both study groups. CONCLUSIONS: cMRI scanning with 1.5 T scanners is safe in patients implanted with the Accent MRI™ conditional pacing system and has no significant effect on the electrical parameters of the device and leads.

Regional and ethnic differences among patients with heart failure in Asia: the Asian sudden cardiac death in heart failure registry.

AIMS: To characterize regional and ethnic differences in heart failure (HF) across Asia. METHODS AND RESULTS: We prospectively studied 5276 patients with stable HF and reduced ejection fraction (≤40%) from 11 Asian regions (China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, and Thailand). Mean age was 59.6 ± 13.1 years, 78.2% were men, and mean body mass index was 24.9 ± 5.1 kg/m2. Majority (64%) of patients had two or more comorbid conditions such as hypertension (51.9%), coronary artery disease (CAD, 50.2%), or diabetes (40.4%). The prevalence of CAD was highest in Southeast Asians (58.8 vs. 38.2% in Northeast Asians). Compared with Chinese ethnicity, Malays (adjusted odds ratio [OR] 1.97, 95% CI 1.63-2.38) and Indians (OR 1.44, 95% CI 1.24-1.68) had higher odds of CAD, whereas Koreans (OR 0.38, 95% CI 0.29-0.50) and Japanese (OR 0.44, 95% CI 0.36-0.55) had lower odds. The prevalence of hypertension and diabetes was highest in Southeast Asians (64.2 and 49.3%, respectively) and high-income regions (59.7 and 46.2%, respectively). There was significant interaction between ethnicity and region, where the adjusted odds were 3.95 (95% CI 2.51-6.21) for hypertension and 4.91 (95% CI 3.07-7.87) for diabetes among Indians from high- vs. low-income regions; and 2.60 (95% CI 1.66-4.06) for hypertension and 2.62 (95% CI 1.73-3.97) for diabetes among Malays from high- vs. low-income regions. CONCLUSIONS: These first prospective multi-national data from Asia highlight the significant heterogeneity among Asian patients with stable HF, and the important influence of both ethnicity and regional income level on patient characteristics. CLINICALTRIALSGOV IDENTIFIER: NCT01633398.

Fever-Induced Brugada Syndrome Is More Common Than Previously Suspected: A Cross-Sectional Study from an Endemic Area.

BACKGROUND: Brugada syndrome (BrS) is defined as presenting of type-1 Brugada pattern (BrP). BrS can also be induced by fever. This study demonstrated a highest prevalence of fever-induced BrS ever reported. METHOD: During May 2014, febrile (oral temperature ≥ 38 °C) and nonfebrile patients underwent standard and high leads (V1 and V2 at 2nd intercostal space) electrocardiogram. Risk factor and cardiac symptoms were recorded. Patients with a persistent of type-1 BrP after fever had subsided were excluded. The prevalence of BrS, type-2 BrP and early repolarization pattern (ERP) were demonstrated. RESULTS: A total of 401 patients, 152 febrile, and 249 nonfebrile, were evaluated. BrS was identified in six febrile patients (five males and one female) and two males in nonfebrile patients. The study demonstrated higher prevalence of BrS in febrile group compared to nonfebrile group (4.0% vs 0.8%, respectively, P = 0.037). Among fever-induced BrS patients, three patients (50.0%) experienced cardiac symptoms before and at the time of presentation and two patients (33.3%) had history of first-degree relative sudden death. No ventricular arrhythmia was observed. All of type-1 BrP disappeared after fever had subsided. We found no difference in prevalence of type-2 BrP in febrile and nonfebrile group (2.0% vs 2.8%, respectively, P > 0.05) as well as ERP (3.3% vs 6.4%, respectively, P > 0.05). CONCLUSIONS: Our study showed a highest prevalence of fever induced BrS ever reported. A larger study of prevalence, risk stratification, genetic test and management of fever-induced BrS should be done, especially in an endemic area.

Fragmented QRS as a Predictor of Appropriate Implantable Cardioverter-defibrillator Therapy.

BACKGROUND: Fragmented QRS (fQRS) has been shown to be a marker of local myocardial conduction abnormalities and a predictor of cardiac events in selected populations. We hypothesized that the presence of a fQRS might predict arrhythmic events in patients who received an implantable cardioverter-defibrillator (ICD), regardless of the indications for implantation. METHODS AND RESULTS: A cohort of 107 consecutive patients (mean age, 53 years; 82% male) who underwent an ICD implantation was studied. We defined fQRS, on a routine 12-lead ECG, as the presence of an additional R wave or notching in the nadir of the S wave in 2 consecutive leads corresponding to a major coronary artery territory. In the presence of bundle branch block, more than 2 notches in the R or S waves in 2 consecutive leads were required to characterize fQRS. Patients were followed for 21.3±23 months for appropriate ICD therapy (antitachycardia pacing and/or shock). ICDs were implanted predominantly in patients with ischemic cardiomyopathy (N=45, 42.1%), followed by Brugada syndrome (N=26, 24.3%). fQRS presented in 42 patients (39.3%). During follow-up, patients with fQRS received more appropriate ICD therapy than those without fQRS (45.2% vs. 10.8%, P<0.0001). After adjustment for covariates, fQRS remained an independent predictor for appropriate ICD therapy (hazard ratio=5.32, 95% confidence interval=2.11-13.37, P<0.0001). CONCLUSION: The presence of fQRS appeared to be directly associated with appropriate ICD therapy.

Predicting arrhythmic event score in Brugada syndrome: Worldwide pooled analysis with internal and external validation.

BACKGROUND: Brugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). Risk predictive scores were previously developed with various performances. OBJECTIVE: The purpose of this study was to create a novel score-Predicting Arrhythmic evenT (PAT)-with internal and external validation. METHODS: A systematic review was performed to identify risk factors for MAE. The odds ratios (ORs) of each factor were pooled across studies. The PAT scoring scheme was developed based on pooled ORs. The PAT score was internally validated with published 105 Asian patients (follow-up 8.0 ± 4.1 [SD] years) and externally validated with unpublished 164 multiracial patients (82.3% White, 14.6% Asian, 3.2% Black; mean follow-up 8.0 ± 6.9 years) with Brugada syndrome. Performances were assessed and compared with previous scores using receiver operating characteristic curve (ROC) analysis. RESULTS: Sixty-seven studies published between 2002 and 2022 from 26 countries (7358 patients) were included. Pooled ORs were estimated, indicating that 15 of 23 risk factors were significant. The PAT score was then developed accordingly. The PAT score had significantly better discrimination (ROC 0.9671) than the BRUGADA-RISK score (ROC 0.7210; P = .006), Shanghai Score System (ROC 0.7079; P = .003), and Sieira et al score (ROC 0.8174; P = .026) in an external validation cohort. PAT score ≥ 10 predicted the first MAE with 95.5% sensitivity and 89.1% specificity (ROC 0.9460) and the recurrent MAE (ROC 0.7061) with 15.4% sensitivity and 93.3% specificity. CONCLUSION: The PAT score was shown to be useful in predicting MAE for primary prevention in patients with Brugada syndrome.

Correction: Mahasing et al. Myocarditis and Pericarditis following COVID-19 Vaccination in Thailand. Vaccines 2023, 11, 749.

The authors wish to make the following corrections to this published paper [...].

Myocarditis and Pericarditis following COVID-19 Vaccination in Thailand.

BACKGROUND: Myocarditis and pericarditis cases following Coronavirus 2019 (COVID-19) vaccination were reported worldwide. In Thailand, COVID-19 vaccines were approved for emergency use. Adverse event following immunization (AEFI) surveillance has been strengthened to ensure the safety of the vaccines. This study aimed to describe the characteristics of myocarditis and pericarditis, and identify the factors associated with myocarditis and pericarditis following COVID-19 vaccination in Thailand. METHOD: We carried out a descriptive study of reports of myocarditis and pericarditis to Thailand's National AEFI Program (AEFI-DDC) between 1 March and 31 December 2021. An unpaired case-control study was conducted to determine the factors associated with myocarditis and pericarditis after the CoronaVac, ChAdOx1-nCoV, BBIBP-CorV, BNT162b2, and mRNA-1273 vaccines. The cases consisted of COVID-19 vaccine recipients who met the definition of confirmed, probable, or suspected cases of myocarditis or pericarditis within 30 days of vaccination. The controls were people who underwent COVID-19 vaccination between 1 March and 31 December 2021, with no adverse reactions documented after vaccination. RESULTS: Among the 31,125 events recorded in the AEFI-DDC after 104.63 million vaccinations, 204 cases of myocarditis and pericarditis were identified. The majority of them were male (69%). The median age was 15 years (interquartile range (IQR): 13-17). The incidence was highest following the BNT162b2 vaccination (0.97 cases per 100,000 doses administered). Ten deaths were reported in this study; no deaths were reported among children who received the mRNA vaccine. Compared with the age-specific incidence of myocarditis and pericarditis in Thailand before the introduction of the COVID-19 vaccination, the incidence of myocarditis and pericarditis after the BNT162b2 vaccine was greater in the 12-17 and 18-20 age groups in both males and females. It was higher after the second dose in 12- to 17-year-olds (2.68 cases per 100,000 doses administered) and highest after the second dose in male 12- to 17-year-olds (4.43 cases per 100,000 doses administered). Young age and a mRNA-based vaccination were associated with myocarditis and pericarditis following administration of the COVID-19 vaccine after multivariate analysis. CONCLUSIONS: Myocarditis and pericarditis following vaccination against COVID-19 were uncommon and mild, and were most likely to affect male adolescents. The COVID-19 vaccine offers the recipients enormous benefits. The balance between the risks and advantages of the vaccine and consistent monitoring of AEFI are essential for management of the disease and identification of AEFI.

Statement from the Asia Summit: Current state of arrhythmia care in Asia.

On May 27, 2022, the Asia Pacific Heart Rhythm Society and the Heart Rhythm Society convened a meeting of leaders from different professional societies of healthcare providers committed to arrhythmia care from the Asia Pacific region. The overriding goals of the meeting were to discuss clinical and health policy issues that face each country for providing care for patients with electrophysiologic issues, share experiences and best practices, and discuss potential future solutions. Participants were asked to address a series of questions in preparation for the meeting. The format of the meeting was a series of individual country reports presented by the leaders from each of the professional societies followed by open discussion. The recorded presentations from the Asia Summit can be accessed at https://www.heartrhythm365.org/URL/asiasummit-22. Three major themes arose from the discussion. First, the major clinical problems faced by different countries vary. Although atrial fibrillation is common throughout the region, the most important issues also include more general issues such as hypertension, rheumatic heart disease, tobacco abuse, and management of potentially life-threatening problems such as sudden cardiac arrest or profound bradycardia. Second, there is significant variability in the access to advanced arrhythmia care throughout the region due to differences in workforce availability, resources, drug availability, and national health policies. Third, collaboration in the area already occurs between individual countries, but no systematic regional method for working together is present.

Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium.

BACKGROUND: The underlying electrophysiological mechanism that causes an abnormal ECG pattern and ventricular tachycardia/ventricular fibrillation (Vt/VF) in patients with the Brugada syndrome (BrS) remains unelucidated. However, several studies have indicated that the right ventricular outflow tract (RVOT) is likely to be the site of electrophysiological substrate. We hypothesized that in patients with BrS who have frequent recurrent VF episodes, the substrate site is the RVOT, either over the epicardium or endocardium; abnormal electrograms would be identified at this location, which would serve as the target site for catheter ablation. METHODS AND RESULTS: We studied 9 symptomatic patients with the BrS (all men; median age 38 years) who had recurrent VF episodes (median 4 episodes) per month, necessitating implantable cardioverter defibrillator discharge. Electroanatomic mapping of the right ventricle, both endocardially and epicardially, and epicardial mapping of the left ventricle were performed in all patients during sinus rhythm. All patients had typical type 1 Brugada ECG pattern and inducible Vt/VF; they were found to have unique abnormal low voltage (0.94±0.79 mV), prolonged duration (132±48 ms), and fractionated late potentials (96±47 ms beyond QRS complex) clustering exclusively in the anterior aspect of the RVOT epicardium. Ablation at these sites rendered Vt/VF noninducible (7 of 9 patients [78%]; 95% confidence interval, 0.40 to 0.97, P=0.015) and normalization of the Brugada ECG pattern in 89% (95% confidence interval, 0.52 to 0.99; P=0.008). Long-term outcomes (20±6 months) were excellent, with no recurrent Vt/VF in all patients off medication (except 1 patient on amiodarone). CONCLUSIONS: The underlying electrophysiological mechanism in patients with BrS is delayed depolarization over the anterior aspect of the RVOT epicardium. Catheter ablation over this abnormal area results in normalization of the Brugada ECG pattern and prevents Vt/VF, both during electrophysiological studies as well as spontaneous recurrent Vt/VF episodes in patients with BrS.

Feasibility, efficacy, and safety of radiofrequency catheter ablation for cardiac arrhythmias: a twelve-year experience in Thailand.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is widely accepted as a curative treatment for many types of cardiac arrhythmias. MATERIAL AND METHOD: The authors retrospectively reviewed 1,193 cases (mean age 45, 41% male) performed in the electrophysiology laboratory at Ramathibodi Hospital from 1996 to 2007. Success rate, recurrence rate and complications were analyzed. RESULTS: Ablations of atrioventricular nodal reentrant tachycardia (AVNRT, 428 cases, 35.9%) and atrioventricular reentrant tachycardia (AVRT, 346 cases, 29%) were the most common procedures. The overall success rate and recurrence rate of RFCA were 88.8% and 6.1% respectively. Complications occurred in 50 patients (4.2%) with 1 death (0.08%). RFCA of AVNRT or AVRT rather than other arrhythmias (Odd ratio 11.46, 95% confidence interval 8.14-16.15, p < 0.001) and adult rather than pediatric patients (Odd ratio for age 1.007, 95% confidence interval 1.003-1.011, p < 0.001) were independent predictors for successful RFCA. CONCLUSION: RFCA of cardiac arrhythmia in our institution is safe and effective.

Brugada syndrome: A comprehensive review of pathophysiological mechanisms and risk stratification strategies.

Brugada syndrome (BrS) is an inherited ion channel channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Originally believed to be predominantly associated with mutations in SCN5A encoding for the cardiac sodium channel, mutations of 18 genes other than SCN5A have been implicated in the pathogenesis of BrS to date. Diagnosis is based on the presence of a spontaneous or drug-induced coved-type ST segment elevation. The predominant electrophysiological mechanism underlying BrS remains disputed, commonly revolving around the three main hypotheses based on abnormal repolarization, depolarization or current-load match. Evidence from computational modelling, pre-clinical and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening ventricular arrhythmic events. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers. Current treatment options include pharmacological therapy to reduce the occurrence of arrhythmic events or to abort these episodes, and interventions such as implantable cardioverter-defibrillator insertion or radiofrequency ablation of abnormal arrhythmic substrate.

Regional Variation of Mortality in Heart Failure With Reduced and Preserved Ejection Fraction Across Asia: Outcomes in the ASIAN-HF Registry.

Background Data comparing outcomes in heart failure (HF) across Asia are limited. We examined regional variation in mortality among patients with HF enrolled in the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry with separate analyses for those with reduced ejection fraction (EF; <40%) versus preserved EF (≥50%). Methods and Results The ASIAN-HF registry is a prospective longitudinal study. Participants with symptomatic HF were recruited from 46 secondary care centers in 3 Asian regions: South Asia (India), Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore), and Northeast Asia (South Korea, Japan, Taiwan, Hong Kong, China). Overall, 6480 patients aged >18 years with symptomatic HF were recruited (mean age: 61.6±13.3 years; 27% women; 81% with HF and reduced rEF). The primary outcome was 1-year all-cause mortality. Striking regional variations in baseline characteristics and outcomes were observed. Regardless of HF type, Southeast Asians had the highest burden of comorbidities, particularly diabetes mellitus and chronic kidney disease, despite being younger than Northeast Asian participants. One-year, crude, all-cause mortality for the whole population was 9.6%, higher in patients with HF and reduced EF (10.6%) than in those with HF and preserved EF (5.4%). One-year, all-cause mortality was significantly higher in Southeast Asian patients (13.0%), compared with South Asian (7.5%) and Northeast Asian patients (7.4%; P<0.001). Well-known predictors of death accounted for only 44.2% of the variation in risk of mortality. Conclusions This first multinational prospective study shows that the outcomes in Asian patients with both HF and reduced or preserved EF are poor overall and worst in Southeast Asian patients. Region-specific risk factors and gaps in guideline-directed therapy should be addressed to potentially improve outcomes. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01633398.