Right Ventricular Outflow Tract Electroanatomical Abnormalities Predict Ventricular Fibrillation Inducibility in Brugada Syndrome
2018; Lippincott Williams & Wilkins; Volume: 11; Issue: 2 Linguagem: Inglês
10.1161/circep.117.005928
ISSN1941-3149
AutoresΚonstantinos P. Letsas, Michael Efremidis, Dimitrios Asvestas, Konstantinos Vlachos, Stamatis Georgopoulos, Gary Tse, Tong Liu, George Bazoukis, Antonios Sideris, Adrián Baranchuk, Joachim R. Ehrlich, Pedro Brugada,
Tópico(s)Cardiac Arrhythmias and Treatments
ResumoHomeCirculation: Arrhythmia and ElectrophysiologyVol. 11, No. 2Right Ventricular Outflow Tract Electroanatomical Abnormalities Predict Ventricular Fibrillation Inducibility in Brugada Syndrome Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessLetterPDF/EPUBRight Ventricular Outflow Tract Electroanatomical Abnormalities Predict Ventricular Fibrillation Inducibility in Brugada Syndrome Konstantinos P. Letsas, MD, Michael Efremidis, MD, Dimitrios Asvestas, MD, Konstantinos Vlachos, MD, Stamatis Georgopoulos, MD, Gary Tse, MBBS, PhD, Tong Liu, MD, PhD, George Bazoukis, MD, Antonios Sideris, MD, Adrian Baranchuk, MD, PhD, Joachim R. Ehrlich, MD and Pedro Brugada, MD Konstantinos P. LetsasKonstantinos P. Letsas From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Michael EfremidisMichael Efremidis From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Dimitrios AsvestasDimitrios Asvestas From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Konstantinos VlachosKonstantinos Vlachos From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Stamatis GeorgopoulosStamatis Georgopoulos From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Gary TseGary Tse From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Tong LiuTong Liu From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , George BazoukisGeorge Bazoukis From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Antonios SiderisAntonios Sideris From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Adrian BaranchukAdrian Baranchuk From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). , Joachim R. EhrlichJoachim R. Ehrlich From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). and Pedro BrugadaPedro Brugada From the Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Greece (K.P.L., M.E., D.A., K.V., S.G., G.B., A.S.); Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, SAR, P.R. China (G.T.); Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, P.R. China (T.L.); Division of Cardiology, Queen's University, Kingston General Hospital, Ontario, Canada (A.B.); Electrophysiology Section, St. Josefs-Hospital, Wiesbaden, Germany (J.R.E.); and Heart Rhythm Management Centre, UZ Brussel-VUB, Belgium (P.B.). Originally published8 Feb 2018https://doi.org/10.1161/CIRCEP.117.005928Circulation: Arrhythmia and Electrophysiology. 2018;11:e005928Electroanatomical mapping has demonstrated abnormal bipolar electrograms at the anterior aspect of the right ventricular outflow tract (RVOT) epicardium along with histopathologic evidence of fibrosis in patients with Brugada syndrome (BrS).1,2 These epicardial abnormalities are believed to serve as the electric substrate for ventricular fibrillation (VF) initiation and maintenance in BrS.1,2 We have recently demonstrated that patients with BrS display wide areas of endocardial unipolar voltage abnormalities that possibly reflect epicardial structural abnormalities at the free wall of the RVOT.3 We hypothesized that electroanatomical abnormalities detected by high-density endocardial unipolar voltage mapping at the RVOT predict VF inducibility during programmed ventricular stimulation (PVS).The study population consisted of 17 asymptomatic probands (15 males, 37.3±10.8 years) with spontaneous type 1 BrS ECG pattern referred for risk stratification with PVS. A comprehensive evaluation including late gadolinium enhancement cardiac magnetic resonance imaging ruled out structural heart disease in all patients. The study was approved by the Hospital Ethics Committee and written informed consent was obtained from all patients.High-density electroanatomical mapping of the RVOT during sinus rhythm was performed as described previously (Methods in the Data Supplement).3 In brief, a minimum of 800 points were sampled to build the RVOT geometry (CARTO 3, Biosense-Webster, CA). An electroanatomical mapping was considered abnormal in the presence of low-voltage areas >1.5 cm2 including ≥3 adjacent points with a bipolar signal amplitude <1 mV and an unipolar signal amplitude <4 mV (Figure [A] and [B]).3 PVS was performed from the right ventricular apex and RVOT sites at 3 drive trains (600, 500, and 400 ms) inserting up to 3 extrastimuli (no <200 ms), and considered positive if VF (lasting ≥30 s or requiring termination because of rapid hemodynamic deterioration) was induced.Continuous data are presented as mean±SD. Continuous variables with and without normal distribution were compared using Student t test and Mann–Whitney U test, respectively. The association between abnormal bipolar and unipolar electroanatomical mapping and VF induction during PVS was determined by means of univariate analysis. A receiver operating characteristics curve analysis was performed to determine the optimal cutoff value of the abnormal area size, defined as the value maximizing the sum of sensitivity and specificity, that predict VF inducibility. A probability of 11 cm2 for low-amplitude unipolar signals (area under the curve, 0.939; sensitivity, 100%; specificity, 73%; P=0.004) and >3.5 cm2 for low-amplitude bipolar signals (area under the curve, 0.856; sensitivity, 83%; specificity, 82%; P=0.018) predict VF inducibility during PVS. None of the BrS subjects displaying normal electroanatomical findings were inducible for VF during PVS. During a mean follow-up period of 8.4±3.9 months, 1 patient received an appropriate implantable cardioverter defibrillator shock.Download figureDownload PowerPointFigure. Right ventricular outflow tract electroanatomical mapping in Brugada syndrome.A, High-density endocardial mapping showing small areas of low-voltage bipolar signals (<1 mV) at the free wall of the right ventricular outflow tract in a patient with Brugada syndrome and inducible ventricular fibrillation during programmed ventricular stimulation; (B) a broad area of abnormal unipolar signals (< 4 mV) was recorded at the same region, possibly reflecting epicardial lesions.High-density endocardial unipolar voltage mapping may prove a valuable tool for the diagnosis and risk stratification of BrS. Using an endocardial unipolar voltage threshold of 4 mV, we showed that patients with BrS, even with no or minimal bipolar voltage lesions, display large areas of abnormal unipolar voltage mapping at the free wall of the RVOT. In a recent study, a similar endocardial unipolar voltage cutoff value for the identification of epicardial bipolar voltage abnormalities in the right ventricle has been proposed (3.9 mV).4 Low-unipolar endocardial area indicates epicardial involvement in patients with no or minimal bipolar endocardial changes.4,5 The identification of large abnormal endocardial unipolar areas that possibly reflect a diseased epicardium may strengthen the diagnosis of BrS. The later may add important information for distinguishing true BrS patients from those with Brugada phenocopies, based on the presence of abnormal and normal maps, respectively.Electroanatomical mapping may additionally improve the prognostic accuracy of PVS in patients with BrS. We demonstrated that BrS patients with broad endocardial unipolar voltage abnormalities are more vulnerable to VF induction during PVS. On the contrary, subjects with normal electroanatomical maps were noninducible. Previous epicardial studies support the present findings.1,2 After epicardial substrate elimination, patients with BrS become noninducible during PVS and the ECG normalizes.1,2 The prognostic significance of this novel electroanatomical marker in asymptomatic individuals with BrS remains to be prospectively validated in the setting of multiparametric risk stratification models.DisclosuresNone.FootnotesThe Data Supplement is available at http://circep.ahajournals.org/lookup/suppl/doi:10.1161/CIRCEP.117.005928/-/DC1.Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org.Correspondence to: Konstantinos P. Letsas, MD, Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Athens 10676, Greece. E-mail [email protected]References1. Nademanee K, Raju H, de Noronha SV, Papadakis M, Robinson L, Rothery S, Makita N, Kowase S, Boonmee N, Vitayakritsirikul V, Ratanarapee S, Sharma S, van der Wal AC, Christiansen M, Tan HL, Wilde AA, Nogami A, Sheppard MN, Veerakul G, Behr ER. Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome.J Am Coll Cardiol. 2015; 66:1976–1986. doi: 10.1016/j.jacc.2015.08.862.CrossrefMedlineGoogle Scholar2. Brugada J, Pappone C, Berruezo A, Vicedomini G, Manguso F, Ciconte G, Giannelli L, Santinelli V. Brugada syndrome phenotype elimination by epicardial substrate ablation.Circ Arrhythm Electrophysiol. 2015; 8:1373–1381. doi: 10.1161/CIRCEP.115.003220.LinkGoogle Scholar3. Letsas KP, Efremidis M, Vlachos K, Georgopoulos S, Karamichalakis N, Asvestas D, Valkanas K, Korantzopoulos P, Liu T, Sideris A. Right ventricular outflow tract high-density endocardial unipolar voltage mapping in patients with Brugada syndrome: evidence for electroanatomical abnormalities [published online ahead of print May 2, 2017].Europace. doi: 10.1093/europace/eux079. https://academic.oup.com/europace/advance-article-abstract/doi/10.1093/europace/eux079/3788900?redirectedFrom=fulltext.Google Scholar4. Venlet J, Piers SRD, Kapel GFL, de Riva M, Pauli PFG, van der Geest RJ, Zeppenfeld K. Unipolar endocardial voltage mapping in the right ventricle: optimal cutoff values correcting for computed tomography-derived epicardial fat thickness and their clinical value for substrate delineation.Circ Arrhythm Electrophysiol. 2017; 10:e005175. doi: 10.1161/CIRCEP.117.005175.LinkGoogle Scholar5. Hutchinson MD, Gerstenfeld EP, Desjardins B, Bala R, Riley MP, Garcia FC, Dixit S, Lin D, Tzou WS, Cooper JM, Verdino RJ, Callans DJ, Marchlinski FE. 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Tse G, Zhang N, Song W, Letsas K, Ngarmukos T, Jeevaratnam K and Liu T (2022) Editorial: Risk Stratification Strategies for Cardiac Rhythm Abnormalities, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.887461, 9 Corbo M, Vitale E, Pesolo M, Casavecchia G, Gravina M, Pellegrino P, Brunetti N and Iacoviello M (2022) Recent Non-Invasive Parameters to Identify Subjects at High Risk of Sudden Cardiac Death, Journal of Clinical Medicine, 10.3390/jcm11061519, 11:6, (1519) Letsas K, Vlachos K, Conte G, Efremidis M, Nakashima T, Duchateau J, Bazoukis G, Frontera A, Mililis P, Tse G, Cheniti G, Takigawa M, Pambrun T, Prappa E, Sacher F, Derval N, Sideris A, Auricchio A, Jais P, Haissaguerre M and Hocini M (2021) Right ventricular outflow tract electroanatomical abnormalities in asymptomatic and high‐risk symptomatic patients with Brugada syndrome: Evidence for a new risk stratification tool?, Journal of Cardiovascular Electrophysiology, 10.1111/jce.15262, 32:11, (2997-3007), Online publication date: 1-Nov-2021. Noheria A and Anderson J (2021) Advances in Mapping and Ablation of Ventricular Fibrillation, Current Treatment Options in Cardiovascular Medicine, 10.1007/s11936-021-00899-1, 23:3, Online publication date: 1-Mar-2021. Tse G, Lee S, Li A, Chang D, Li G, Zhou J, Liu T and Zhang Q (2021) Automated Electrocardiogram Analysis Identifies Novel Predictors of Ventricular Arrhythmias in Brugada Syndrome, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2020.618254, 7 Li K, Lee S, Yin C, Liu T, Ngarmukos T, Conte G, Yan G, Sy R, Letsas K and Tse G (2020) Brugada syndrome: A comprehensive review of pathophysiological mechanisms and risk stratification strategies, IJC Heart & Vasculature, 10.1016/j.ijcha.2020.100468, 26, (100468), Online publication date: 1-Feb-2020. 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February 2018Vol 11, Issue 2 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.117.005928PMID: 29437762 Manuscript receivedOctober 2, 2017Manuscript acceptedJanuary 12, 2018Originally publishedFebruary 8, 2018 KeywordsgadoliniumBrugada syndromemagnetic resonance imagingventricular fibrillationvoltage mappingPDF download Advertisement SubjectsElectrophysiologySudden Cardiac DeathVentricular Fibrillation
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