Publications by authors named "Koonlawee Nademanee"

66 Publications

Radiofrequency ablation in Brugada syndrome.

Heart Rhythm 2021 Oct;18(10):1805-1806

Center of Excellence in Arrhythmia Research Chulalongkorn University, Chulalongkorn University, Bangkok, Thailand; Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Pacific Rim Electrophysiology Research Institute at Bumrungrad Hospital, Bangkok, Thailand. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2021.08.005DOI Listing
October 2021

2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families.

J Arrhythm 2021 Jun 8;37(3):481-534. Epub 2021 Apr 8.

The First Affiliated Hospital of Nanjing Medical University Nanjing China.

This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.
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http://dx.doi.org/10.1002/joa3.12449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207384PMC
June 2021

Role of Catheter Ablation for Ventricular Arrhythmias in Brugada Syndrome.

Curr Cardiol Rep 2021 04 24;23(5):54. Epub 2021 Apr 24.

Faculty of Medicine, Division of Cardiovascular Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, 10330, Thailand.

Purpose Of Review: To discuss the role of catheter ablation in treating life-threatening ventricular arrhythmias associated with Brugada syndrome (BrS), by presenting recent findings of BrS arrhythmogenic substrate, mechanisms underlying ventricular arrhythmias, and how they can be treated with catheter ablation.

Recent Findings: Almost three decades ago when the clinical entity of Brugada syndrome (BrS) was described in patients who had abnormal coved-type ST elevation in the right precordial EKG leads in patients who had no apparent structural heart disease but died suddenly from ventricular fibrillation. Since its description, the syndrome has galvanized explosive research in this field over the past decades, driving major progress toward better understanding of BrS, gaining knowledge of the genetic pathophysiology and risk stratification of BrS, and creating significant advances in therapeutic modalities. One of such advances is the ability for electrophysiologists to map and identify the arrhythmogenic substrate sites of BrS, which serve as good target sites for catheter ablation. Subsequently, several studies have shown that catheter ablation of these substrates normalizes the Brugada ECG pattern and is very effective in eliminating these substrates and preventing recurrent VF episodes. Catheter ablation has become an important addition for treatment of symptomatic BrS patients with recurrent VT/VF episodes.
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http://dx.doi.org/10.1007/s11886-021-01479-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068636PMC
April 2021

Genetic risks and association with severe COVID-19 among global populations.

Pathog Glob Health 2021 06 3;115(4):209-210. Epub 2021 Feb 3.

Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

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http://dx.doi.org/10.1080/20477724.2021.1881371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168748PMC
June 2021

Reply: J-Wave Syndromes: Where's the Scar?

JACC Clin Electrophysiol 2020 12;6(14):1863-1864

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http://dx.doi.org/10.1016/j.jacep.2020.10.003DOI Listing
December 2020

Phenotype prediction and characterization of 25 pharmacogenes in Thais from whole genome sequencing for clinical implementation.

Sci Rep 2020 11 3;10(1):18969. Epub 2020 Nov 3.

Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Publicly available pharmacogenomics (PGx) databases enable translation of genotype data into clinically actionable information. As variation within pharmacogenes is population-specific, this study investigated the spectrum of 25 clinically relevant pharmacogenes in the Thai population (n = 291) from whole genome sequencing. The bioinformatics tool Stargazer was used for phenotype prediction, through assignment of alleles and detection of structural variation. Known and unreported potentially deleterious PGx variants were identified. Over 25% of Thais carried a high-risk diplotype in CYP3A5, CYP2C19, CYP2D6, NAT2, SLCO1B1, and UGT1A1. CYP2D6 structural variants accounted for 83.8% of all high-risk diplotypes. Of 39 known PGx variants identified, six variants associated with adverse drug reactions were common. Allele frequencies of CYP3A5*3 (rs776746), CYP2B6*6 (rs2279343), and NAT2 (rs1041983) were significantly higher in Thais than East-Asian and global populations. 121 unreported variants had potential to exert clinical impact, majority were rare and population-specific, with 60.3% of variants absent from gnomAD database. This study demonstrates the population-specific variation in clinically relevant pharmacogenes, the importance of CYP2D6 structural variation detection in the Thai population, and potential of unreported variants in explaining drug response. These findings are essential in development of dosing guidelines, PGx testing, clinical trials, and drugs.
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http://dx.doi.org/10.1038/s41598-020-76085-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641128PMC
November 2020

Structurally Abnormal Myocardium Underlies Ventricular Fibrillation Storms in a Patient Diagnosed With the Early Repolarization Pattern.

JACC Clin Electrophysiol 2020 10 16;6(11):1395-1404. Epub 2020 Sep 16.

Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam University Medical Centers, Amsterdam, the Netherlands; IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Pessac-Bordeaux, France. Electronic address:

Objectives: The aim of this study was to investigate the mechanism underlying QRS-slurring in a patient with the early repolarization pattern in the electrocardiogram (ECG) and ventricular fibrillation (VF) storms.

Background: The early repolarization pattern refers to abnormal ending of the QRS complex in subjects with structurally normal hearts and has been associated with VF.

Methods: We studied a patient with slurring of the QRS complex in leads II, III, and aVF of the ECG and recurrent episodes of VF. Echocardiographic and imaging studies did not reveal any abnormalities. Endocardial mapping was normal but subxyphoidal epicardial access was not possible. Open chest epicardial mapping was performed.

Results: Mapping showed that the inferior right ventricular free wall activated the latest with local J-waves in unipolar electrograms. The last moment of epicardial activation concurred with QRS-slurring in the ECG whereas the J-waves in the local unipolar electrograms occurred in the ST-segment of the ECG. Myocardial biopsies obtained from the late activated tissue showed severe fibrofatty alterations in the inferior right ventricular wall where fractionation and local J-waves were present. After ablation, the early repolarization pattern in the ECG disappeared and arrhythmias have been absent since (follow-up 18 months).

Conclusions: In this patient, the electrocardiographic early repolarization pattern was caused by late activation due to structurally abnormal myocardium. The late activated areas were marked by J-waves in local electrograms. Ablation of these regions prevented arrhythmia recurrence and normalized the ECG.
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http://dx.doi.org/10.1016/j.jacep.2020.06.027DOI Listing
October 2020

Two Faces of Brugada Syndrome: Electrical and Structural Diseases.

JACC Clin Electrophysiol 2020 10;6(11):1364-1366

Waon Therapy Research Institute, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.jacep.2020.07.006DOI Listing
October 2020

2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families.

Heart Rhythm 2021 01 19;18(1):e1-e50. Epub 2020 Oct 19.

The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.
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http://dx.doi.org/10.1016/j.hrthm.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194370PMC
January 2021

Atrial fibrillation ablation in the 21st century: Almost no stroke risk?

Heart Rhythm 2020 12 13;17(12):2100-2101. Epub 2020 Aug 13.

Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2020.08.008DOI Listing
December 2020

Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand.

Heart Rhythm 2020 12 30;17(12):2145-2153. Epub 2020 Jun 30.

Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Pacific Rim Electrophysiology Research Institute, Bumrungrad Hospital, Bangkok, Thailand.

Background: Mutations in SCN5A are rarely found in Thai patients with Brugada syndrome (BrS). Recent evidence suggested that common genetic variations may underlie BrS in a complex inheritance model.

Objective: The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand.

Methods: We conducted a genome-wide association study (GWAS) to explore the association of common variants in 154 Thai BrS cases and 432 controls. We sequenced SCN5A in 131 cases and 205 controls. Variants were classified according to current guidelines, and case-control association testing was performed for rare and low-frequency variants.

Results: Two loci were significantly associated with BrS. The first was near SCN5A/SCN10A (lead marker rs10428132; odds ratio [OR] 2.4; P = 3 × 10). Conditional analysis identified a novel independent signal in the same locus (rs6767797; OR 2.3; P = 2.7 × 10). The second locus was near HEY2 (lead marker rs3734634; OR 2.5; P = 7 × 10). Rare (minor allele frequency [MAF] <0.0001) coding variants in SCN5A were found in 8 of the 131 cases (6.1% in cases vs 2.0% in controls; P = .046; OR 3.3; 95% confident interval [CI] 1.0-11.1), but an enrichment of low-frequency (MAF<0.001 and >0.0001) variants also was observed in cases, with 1 variant (SCN5A: p.Arg965Cys) detected in 4.6% of Thai BrS patients vs 0.5% in controls (P = 0.015; OR 9.8; 95% CI 1.2-82.3).

Conclusion: The genetic basis of BrS in Thailand includes a wide spectrum of variant frequencies and effect sizes. As previously shown in European and Japanese populations, common variants near SCN5A and HEY2 are associated with BrS in the Thai population, confirming the transethnic transferability of these 2 major BrS loci.
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http://dx.doi.org/10.1016/j.hrthm.2020.06.027DOI Listing
December 2020

Mapping and Ablation of Ventricular Fibrillation Associated With Early Repolarization Syndrome.

Circulation 2019 10 23;140(18):1477-1490. Epub 2019 Sep 23.

Bhumibol Adulyadej RTAF Hospital, Bangkok Thailand (G.V.).

Background: We conducted a multicenter study to evaluate mapping and ablation of ventricular fibrillation (VF) substrates or VF triggers in early repolarization syndromes (ERS) or J-wave syndrome (JWS).

Methods: We studied 52 patients with ERS (4 women; median age, 35 years) with recurrent VF episodes. Body surface electrocardiographic imaging and endocardial and epicardial electroanatomical mapping of both ventricles were performed during sinus rhythm and VF for localization of triggers, substrates, and drivers. Ablations were performed on VF substrates, defined as areas that had late depolarization abnormalities characterized by low-voltage fractionated late potentials, and VF triggers.

Results: Fifty-one of the 52 patients had detailed mapping that revealed 2 phenotypes: group 1 had late depolarization abnormalities predominantly at the right ventricular (RV) epicardium (n=40), and group 2 had no depolarization abnormalities (n=11). Group 1 can be subcategorized into 2 groups: Group 1A included 33 patients with ERS with Brugada electrocardiographic pattern, and group 1B included 7 patients with ERS without Brugada electrocardiographic pattern. Late depolarization areas colocalize with VF driver areas. The anterior RV outflow tract/RV epicardium and the RV inferior epicardium are the major substrate sites for group 1. The Purkinje network is the leading underlying VF trigger in group 2 that had no substrates. Ablations were performed in 43 patients: 31 and 5 group 1 patients had only VF substrate ablation and VF substrates plus VF trigger, respectively (mean, 1.4±0.6 sessions); 6 group 2 patients and 1 patient without group classification had only Purkinje VF trigger ablation (mean, 1.2±0.4 sessions). Ablations were successful in reducing VF recurrences (<0.0001). After follow-up of 31±26 months, 39 (91%) had no VF recurrences.

Conclusions: There are 2 phenotypes of ERS/J-wave syndrome: one with late depolarization abnormality as the underlying mechanism of high-amplitude J-wave elevation that predominantly resides in the RV outflow tract and RV inferolateral epicardium, serving as an excellent target for ablation, and the other with pure ERS devoid of VF substrates but with VF triggers that are associated with Purkinje sites. Ablation is effective in treating symptomatic patients with ERS/J-wave syndrome with frequent VF episodes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039022DOI Listing
October 2019

Depolarization versus repolarization abnormality underlying inferolateral J-wave syndromes: New concepts in sudden cardiac death with apparently normal hearts.

Heart Rhythm 2019 05 2;16(5):781-790. Epub 2018 Nov 2.

IHU LIRYC, Electrophysiology and Heart Modeling Institute, Bordeaux, France; University of Bordeaux, U1045, Bordeaux, France.

Early repolarization indicates a distinct electrocardiographic phenotype affecting the junction between the QRS complex and the ST segment in inferolateral leads (inferolateral J-wave syndromes). It has been considered a benign electrocardiographic variant for decades, but recent clinical studies have demonstrated its arrhythmogenicity in a small subset, supported by experimental studies showing transmural dispersion of repolarization. Here we review the current knowledge and the issues of risk stratification that limit clinical management. In addition, we report on new mapping data of patients refractory to pharmacologic treatment using high-density electrogram mapping at the time of inscription of J wave. These data demonstrate that distinct substrates, delayed depolarization, and abnormal early repolarization underlie inferolateral J-wave syndromes, with significant implications. Finally, based on these data, we propose a new simplified mechanistic classification of sudden cardiac deaths without apparent structural heart disease.
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http://dx.doi.org/10.1016/j.hrthm.2018.10.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486498PMC
May 2019

Endocardial Ablation Approach for Brugada Syndrome: An Important First Step or a Quixotic Quest.

Circ Arrhythm Electrophysiol 2018 08;11(8):e006675

Hopital Cardiologique du Haut-Leveque, Center Hospitalier Universitaire Bordeaux, University Hospital Institutions L'Institut de Rhythmologie et Modelisation Cardiaque France (M.H.).

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http://dx.doi.org/10.1161/CIRCEP.118.006675DOI Listing
August 2018

Localized Structural Alterations Underlying a Subset of Unexplained Sudden Cardiac Death.

Circ Arrhythm Electrophysiol 2018 07;11(7):e006120

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, France (M. Haïssaguerre, M. Hocini, G.C., J.D., F.S., S.P., H.C., M.T., A.D., R.M., N.D., P.B., P.R., S.P., T.P., N.K., G.M., X.P., C.D., L.L., R.C., P.J., D.B., E.V., M.P., R.W., O.B., R.D.).

Background: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported.

Methods: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations.

Results: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (<0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15, =0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up.

Conclusions: This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism.
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http://dx.doi.org/10.1161/CIRCEP.117.006120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661047PMC
July 2018

Repolarization Versus Depolarization Defects in Brugada Syndrome: A Tale of 2 Different Electrophysiologic Settings?

JACC Clin Electrophysiol 2017 04 29;3(4):364-366. Epub 2017 Mar 29.

Heart Centre, Academic Medical Centre in Amsterdam, Amsterdam, the Netherlands; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia.

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http://dx.doi.org/10.1016/j.jacep.2017.01.011DOI Listing
April 2017

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

Pacing Clin Electrophysiol 2018 02 10;41(2):214-217. Epub 2017 Oct 10.

Department of Cardiology, National Heart Centre Singapore, Singapore.

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.
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http://dx.doi.org/10.1111/pace.13175DOI Listing
February 2018

Epicardial substrate ablation for Brugada syndrome.

Heart Rhythm 2017 03 12;14(3):457-461. Epub 2016 Dec 12.

Hopital Cardiologique du Haut-Leveque, CHU Bordeaux, IHU LIRYC, Bordeaux, France.

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http://dx.doi.org/10.1016/j.hrthm.2016.12.001DOI Listing
March 2017

Will we be able to cure brugada syndrome?

Heart Rhythm 2016 11 17;13(11):2159-2160. Epub 2016 Aug 17.

Pacific Rim Electrophysiology Research Institute, Bangkok Thailand, and Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2016.08.025DOI Listing
November 2016

Ablation of complex fractionated electrograms is useful for catheter ablation of persistent atrial fibrillation: Protagonist point of view.

Heart Rhythm 2016 10 1;13(10):2098-100. Epub 2016 Jul 1.

Pacific Rim Electrophysiology Research Institute, Los Angeles, California and Bangkok, Thailand. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2016.06.036DOI Listing
October 2016

Epicardial Substrate Ablation in Brugada Syndrome: Time for a Randomized Trial!

Circ Arrhythm Electrophysiol 2015 Dec;8(6):1306-8

From the Heart Centre, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.A.M.W.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); The Pacific Rim Electrophysiology Research Institute, Los Angeles, CA (K.N.); and Bangkok Heart Hospital, Bangkok, Thailand (K.N.).

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http://dx.doi.org/10.1161/CIRCEP.115.003500DOI Listing
December 2015

Fibrosis, Connexin-43, and Conduction Abnormalities in the Brugada Syndrome.

J Am Coll Cardiol 2015 Nov;66(18):1976-1986

Cardiovascular Sciences, St. George's, University of London, London, United Kingdom. Electronic address:

Background: The right ventricular outflow tract (RVOT) is acknowledged to be responsible for arrhythmogenesis in Brugada syndrome (BrS), but the pathophysiology remains controversial.

Objectives: This study assessed the substrate underlying BrS at post-mortem and in vivo, and the role for open thoracotomy ablation.

Methods: Six whole hearts from male post-mortem cases of unexplained sudden death (mean age 23.2 years) with negative specialist cardiac autopsy and familial BrS were used and matched to 6 homograft control hearts by sex and age (within 3 years) by random risk set sampling. Cardiac autopsy sections from cases and control hearts were stained with picrosirius red for collagen. The RVOT was evaluated in detail, including immunofluorescent stain for connexin-43 (Cx43). Collagen and Cx43 were quantified digitally and compared. An in vivo study was undertaken on 6 consecutive BrS patients (mean age 39.8 years, all men) during epicardial RVOT ablation for arrhythmia via thoracotomy. Abnormal late and fractionated potentials indicative of slowed conduction were identified, and biopsies were taken before ablation.

Results: Collagen was increased in BrS autopsy cases compared with control hearts (odds ratio [OR]: 1.42; p = 0.026). Fibrosis was greatest in the RVOT (OR: 1.98; p = 0.003) and the epicardium (OR: 2.00; p = 0.001). The Cx43 signal was reduced in BrS RVOT (OR: 0.59; p = 0.001). Autopsy and in vivo RVOT samples identified epicardial and interstitial fibrosis. This was collocated with abnormal potentials in vivo that, when ablated, abolished the type 1 Brugada electrocardiogram without ventricular arrhythmia over 24.6 ± 9.7 months.

Conclusions: BrS is associated with epicardial surface and interstitial fibrosis and reduced gap junction expression in the RVOT. This collocates to abnormal potentials, and their ablation abolishes the BrS phenotype and life-threatening arrhythmias. BrS is also associated with increased collagen throughout the heart. Abnormal myocardial structure and conduction are therefore responsible for BrS.
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http://dx.doi.org/10.1016/j.jacc.2015.08.862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631798PMC
November 2015

ST-Segment Elevation and Fractionated Electrograms in Brugada Syndrome Patients Arise From the Same Structurally Abnormal Subepicardial RVOT Area but Have a Different Mechanism.

Circ Arrhythm Electrophysiol 2015 Dec 19;8(6):1382-92. Epub 2015 Oct 19.

From the Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (J.N.t.S., R.C., C.E.C., A.H.G.D., J.R.d.G., H.L.T., A.A.M.W., J.M.T.d.B., P.F.H.M.v.D.); Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands (J.N.t.S., J.M.T.d.B.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Pacific Rim Electrophysiology Research Institute, Los Angeles, CA (K.N.).

Background: Brugada syndrome (BrS) is characterized by a typical ECG pattern. We aimed to determine the pathophysiologic basis of the ST-segment in the BrS-ECG with data from various epicardial and endocardial right ventricular activation mapping procedures in 6 BrS patients and in 5 non-BrS controls.

Methods And Results: In 7 patients (2 BrS and 5 controls) with atrial fibrillation, an epicardial 8×6 electrode grid (interelectrode distance 1 mm) was placed epicardially on the right ventricular outflow tract (RVOT) before video-assisted thoracoscopic surgical pulmonary vein isolation. In 2 other BrS patients, endocardial, epicardial RV (CARTO), and body surface mapping was performed. In 2 additional BrS patients, we performed decremental preexcitation of the RVOT before endocardial RV mapping. During video-assisted thoracoscopic surgical pulmonary vein isolation and CARTO mapping, BrS patients (n=4) showed greater activation delay and more fractionated electrograms in the RVOT region than controls. Ajmaline administration increased the region with fractionated electrograms, as well as ST-segment elevation. Preexcitation of the RVOT (n=2) resulted in ECGs that supported the current-to-load mismatch hypothesis for ST-segment elevation. Body surface mapping showed that the area with ST-segment elevation anatomically correlated with the area of fractionated electrograms and activation delay at the RVOT epicardium.

Conclusions: ST-segment elevation and epicardial fractionation/conduction delay in BrS patients are most likely related to the same structural subepicardial abnormalities, but the mechanism is different. ST-segment elevation may be caused by current-to-load mismatch, whereas fractionated electrograms and conduction delay are expected to be caused by discontinuous conduction in the same area with abnormal myocardium.
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http://dx.doi.org/10.1161/CIRCEP.115.003366DOI Listing
December 2015

Benefits and risks of catheter ablation in elderly patients with atrial fibrillation.

Heart Rhythm 2015 Jan 11;12(1):44-51. Epub 2014 Oct 11.

Pacific Rim Electrophysiology Research Institute at White Memorial Hospital, Los Angeles, California, and Bangkok, Thailand.

Background: The benefits of catheter ablation for elderly patients with atrial fibrillation (AF) with respect to mortality and stroke reductions remain unclear.

Objective: The purpose of this study was to evaluate the safety and efficacy, including long-term outcomes, of catheter ablation for maintaining normal sinus rhythm (NSR) in elderly patients with AF.

Methods: We evaluated 587 elderly patients (age ≥75 years) with AF. Of the 324 who were eligible for ablation, 261 (group 1) underwent ablation guided by complex fractionated atrial electrogram. The remaining 63 patients (group 2) either declined or were not suitable for ablation. The end-points were NSR, stroke, death, and major bleeding.

Results: Two hundred sixteen patients (83%) remained in NSR compared to only 14 group 2 patients (22%; mean follow-up 3 ± 2.5 years, P <.001). The 1- and 5-year survival rates for group 1 with NSR, group 1 with AF, and group 2 patients were 98% and 87%, 86% and 52%, and 97% and 42%, respectively (P <.0001). NSR was an independent favorable parameter for survival (hazard ratio [HR] 0.36; 95% CI, 0.02-0.63, p = 0.0005), whereas older age (HR 1.09, 95% CI 1.01-1.16, P = .02) and depressed ejection fraction <40% (HR 2.38, 95% CI 1.28-4.4, P = .006) were unfavorable. Warfarin therapy was discontinued in 169 of the 216 group 1 patients (78%) who maintained NSR and had only 3% 5-year stroke/bleeding rates compared to 16% in group 2 (P <.001).

Conclusion: Elderly patients with AF benefit from AF ablation, which is safe and effective in maintaining sinus rhythm and is associated with lower mortality and stroke risks.
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http://dx.doi.org/10.1016/j.hrthm.2014.09.049DOI Listing
January 2015

Overlapping risks of early repolarization and Brugada syndrome.

J Am Coll Cardiol 2014 May 2;63(20):2139-2140. Epub 2014 Apr 2.

Pacific Rim Electrophysiology Research Institute, Los Angeles, California; Pacific Rim Electrophysiology Research Institute, Bangkok, Thailand.

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http://dx.doi.org/10.1016/j.jacc.2014.02.585DOI Listing
May 2014

Dabigatran versus warfarin anticoagulation before and after catheter ablation for the treatment of atrial fibrillation.

J Interv Card Electrophysiol 2013 Sep 6;37(3):233-9. Epub 2013 Jun 6.

Oakland University William Beaumont School of Medicine and Beaumont Hospital, Royal Oak, MI 48073, USA.

Background: Systemic thromboembolism and bleeding remain the two most common and serious complications of catheter ablation of atrial fibrillation. A variety of periprocedure anticoagulation strategies have been proposed to mitigate these risks. Although operators are now routinely administering dabigatran for anticoagulation in this setting, its relative safety and effectiveness compared to warfarin are unknown.

Methods And Results: A total of 202 patients received dabigatran as part of their periprocedural anticoagulation regimen at the time of initial or redo catheter ablation for symptomatic atrial fibrillation. A comparison group of 202 patients treated with warfarin was randomly selected from patients undergoing atrial fibrillation (AF) ablation during the same time period. AF types were paroxysmal in 223 patients, persistent in 158 patients, and longstanding persistent in 13 patients. Mean age was 60.0 ± 10.5 years, 55 % had a history of hypertension, and mean CHADS-VASc score was 1.7 ± 1.3. "Continuous" warfarin or dabigatran was administered in 80 and 32 % of patients, respectively. Time to first dose of dabigatran post-procedure was 12.2 ± 10.3 h. Two dabigatran and no warfarin-treated patients had systemic thromboembolism (p = NS); five dabigatran and three warfarin-treated patients had bleeding complications (p = NS, combined endpoint p = 0.116). One dabigatran patient had severe pericardial bleeding (3 L blood loss).

Conclusions: In a retrospective pilot trial comparing the risks of systemic thromboembolism or bleeding complications in patients treated with warfarin or dabigatran anticoagulation, the outcomes were similar. A prospective trial is warranted.
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http://dx.doi.org/10.1007/s10840-013-9800-zDOI Listing
September 2013

Exercise and vagal reflex in long QT syndrome type 1.

J Am Coll Cardiol 2012 Dec 14;60(24):2525-6. Epub 2012 Nov 14.

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http://dx.doi.org/10.1016/j.jacc.2012.08.1007DOI Listing
December 2012

Brugada syndrome: two decades of progress.

Circ J 2012 14;76(12):2713-22. Epub 2012 Nov 14.

Cardiovascular Research and Prevention Center, Bhumibol Adulyadej Hospital and Pacific Rim Electrophysiology Research, Bangkok, Thailand.

Two decades ago, a series of 8 idiopathic ventricular fibrillation patients who each had an abnormal ECG (right bundle branch block with coved-type ECG), but otherwise had normal hearts were described by Brugada and Brugada. Since then, the clinical entity has become known as Brugada syndrome (BS). Shortly thereafter, mutations of the SCN5A gene that encodes for the α-subunit of the sodium channel were found, galvanizing the field of ion channelopathies following in the footsteps of the breakthrough in long QT syndrome. Over the past 20 years, extensive research in this field has produced major progress toward better understanding of BS and the gaining of knowledge of the genetic background, pathophysiology and new management. Two consensus reports were published to help define the diagnostic criteria, risk stratification and management of BS patients. However, there are controversies. In this review, we will share our experiences of BS patients in Thailand and discuss advances in many aspects of the syndrome (ie, genetics and pathophysiology) and some of these pertinent controversies, as well as new treatment of the syndrome with catheter ablation.
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http://dx.doi.org/10.1253/circj.cj-12-1352DOI Listing
May 2013
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