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J-Waves in Epicardial Electrograms Can Guide Ablation of Arrhythmogenic Substrates

2019; Lippincott Williams & Wilkins; Volume: 124; Issue: 2 Linguagem: Inglês

10.1161/circresaha.118.314414

1524-4571

Bastiaan J. Boukens, Tobias Opthof, Ruben Coronel,

ECG Monitoring and Analysis

HomeCirculation ResearchVol. 124, No. 2J-Waves in Epicardial Electrograms Can Guide Ablation of Arrhythmogenic Substrates Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBJ-Waves in Epicardial Electrograms Can Guide Ablation of Arrhythmogenic Substrates Bastiaan J. Boukens, Tobias Opthof and Ruben Coronel Bastiaan J. BoukensBastiaan J. Boukens From the Department of Medical Biology (B.J.B.), Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, the Netherlands , Tobias OpthofTobias Opthof Department of Experimental Cardiology (T.O., R.C.), Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, the Netherlands and Ruben CoronelRuben Coronel Correspondence to Ruben Coronel, MD, PhD, Department of Experimental Cardiology, Academic Medical Center, Room K2-108, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Email E-mail Address: [email protected] Department of Experimental Cardiology (T.O., R.C.), Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, the Netherlands IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, France (R.C.). Originally published17 Jan 2019https://doi.org/10.1161/CIRCRESAHA.118.314414Circulation Research. 2019;124:205–207Ablation of the arrhythmogenic substrate in patients with the early repolarization pattern (ERP) is an effective, novel therapeutic option. We propose that in these patients, J-waves in epicardially recorded unipolar electrograms mark late activated myocardium and may help guide ablation.In 1924, when Willem Einthoven received the Nobel prize for the description of the ECG it was evident that the P- and QRS-waves were caused by depolarization of atrial and ventricular myocardium, respectively and that the T-wave resulted from repolarization of the ventricular myocardium. In 1930, a group of patients was presented with an abnormality preceding the QRS complex. It did not take long before aberrant, premature ventricular activation was shown to constitute the underlying mechanism of this delta wave.1 Although abnormalities at the end of the QRS complex have been recognized for over 80 years, these have not been linked to late activation but, to early repolarization.2 We and others2 consider the nomenclature of ERP unfortunate because its underlying mechanism has not been firmly established.2 Nevertheless, in accordance with the consensus article of Macfarlane et al3 from 2015, we will use ERP to refer to J-waves in the body surface ECG, even when these are not caused by early repolarization but by late activation or excitation failure. Although the ERP was initially considered to be benign, Haissaguerre4 and Tikkanen5 showed that the presence of a J-wave in the ECG associates with increased risk of sudden death. They demonstrated that the ERP with a flat ST segment is malignant.3Local J-Waves Related to Late ActivationPatients with the ERP in the ECG present with J-waves in unipolar electrograms (uEG) as well.6 These J-waves are thought to be the underlying cause of the ECG abnormality.7 Whether these J-waves give rise to corresponding J-waves (the ERP) in the ECG depends on the degree of canceling, the mass of the tissue affected and the ECG lead.7 It is conceivable that the 2 phenomena are uncorrelated and that J-waves in uEGs do not necessarily coincide with the ERP in the ECG.8 Recent data show local J-waves in uEGs occurring after the characteristic abnormalities following the QRS complex (slurring, notching, J-waves) in the ECG of patients with ERP.8 In these patients, the typical changes in ERP coincided with late local activation.8Indeed, J-waves in local uEGs can be induced by slowing conduction as a result of regional infusion of a sodium channel blocker.1,9If late local activation causes the ERP in the ECG, the question can be raised why patients show local J-waves in uEGs whereas controls do not. We posit that J-waves in uEGs occur in late activated myocardium even without excessive phase-1 repolarization (Figure). To illustrate this we generated uEGs from a single strand of 58 myocytes (with human action potentials generated by the Ten Tusscher model) based on local action potentials (black) and the average of all action potentials in the strand (gray) according to the model by Potse et al.10 When local activation is early (Figure, panel A), an RS complex is generated, as expected. The local phase-1 repolarization of the action potential coincides with the RS complex. However, when local activation is late (Figure, panels B and C) phase-1 repolarization brings the membrane potential temporarily negative to the ensemble average of all cardiomyocytes in the strand. This leads to a J-wave in the uEG, (Figure, panels B and C, top). Thus, the amplitude and timing of a local J-wave depend on the local activation time (Figure, panel D). As a consequence, late activated tissue is characterized by a prominent J-wave, especially in subepicardial myocardium where the transient outward current, responsible for early repolarization, is larger than at the endocardium. The J-wave amplitude will increase when phase-1 repolarization is larger (not shown). Importantly, the amplitude and timing of this J-wave increase as a function of the activation delay (Figure, panel D).Download figureDownload PowerPointFigure. Local J-waves in unipolar electrograms (uEGs) are because of normal phase-1 repolarization and are caused by late activation. A–C, show the simulated membrane potential in black (zoomed in on phase-1 of the action potential: inset), the location independent VR (reference potential, sum of all membrane potentials) in gray and the computed unipolar electrograms (top) according to Potse et al.10 The graph in D indicates the relation of local activation (maximum dV/dt of the local action potential) and the time of peak (blue) and the amplitude (in red) of the J-wave in the unipolar electrogram. E, Schematic representations of local unipolar electrograms in the setting of late activation and excitation failure. The graph in F is a schematic representation of the relation between local activation and the amplitude of the J-wave peak in local unipolar electrograms recorded from the epicardium of patients with the early repolarization pattern. The red area defines an abnormal relation between AT and J-wave amplitude or late activation. This area can be defined in individual patients and may serve as a guide to ablate areas with the corresponding uEGs. Ablating the regions that activate after the end of the QRS complex or those that do not follow the linear AT-J relationship may have an antiarrhythmic effect.Amplitude and Timing of Local J-Waves as Indicator for AblationIn Brugada Syndrome patients, local J-waves are commonly preceded by a large S (Figure, red circle in panel E) whereas J-waves in the ERP are often preceded by an R wave (without ST-segment elevation, Figure, panel E, blue circle). Both types of J-waves have been observed in the same Brugada syndrome patient, and the combination is considered more arrhythmogenic than the presence of only one type.11 J-waves in Brugada syndrome patients can be explained by current-to-load mismatch and excitation failure.12 These type of J-waves are not correlated with late activation according to the physiological relation in the Figure, panel D. In the case of excitation failure, there is no activation and early remote activity will be detected.The relation between the amplitude of the peak of the J-wave and the local activation time may be used (Figure, panel F) to differentiate between pathological and nonpathological local J-waves. This relation can be created by plotting the timing of the J-wave peak relative to local activation time in individual patients. If the peak of the local J-wave occurs before the end of the QRS complex, the J-wave is considered not pathological as long as the amplitude follows the AT-J peak relationship (blue dot in the Figure, panel F). If the J-wave occurs in tissue that is activated later than the end of the QRS complex, it is pathological (black dot in the Figure, panel F). If the J-wave occurs in early activated tissue and does not follow the physiological relation, it is pathological, because it results from excitation failure and not from physiological early phase-1 repolarization (red dot in the Figure, panel F). These considerations can be used to help guide ablation to sites of late activation or excitation failure that form the basis for lethal arrhythmias. These notions are relevant because epicardial ablation therapy has emerged as a successful option for some patients with the ERP and the Brugada syndrome.13–15ConclusionsLocal J-waves in uEGs are caused by normal phase-1 repolarization and emerge in late activate tissue. Local J-waves that occur in early activated tissue, or in tissue that is activated following the end of the QRS complex, is pathological. This concept may help to guide ablation of arrhythmogenic substrates.AcknowledgmentsB.J. Boukens received support from the Dutch Heart Foundation (2016T047). R. Coronel is supported by the Leducq International network of Excellence (RHYTHM project: 16CVD02).FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Ruben Coronel, MD, PhD, Department of Experimental Cardiology, Academic Medical Center, Room K2-108, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Email r.[email protected]uva.nlReferences1. Boukens BJ, Janse MJ. Brief history of arrhythmia in the WPW syndrome - the contribution of George Ralph Mines.J Physiol. 2013; 591:4067–4071. doi: 10.1113/jphysiol.2013.259598CrossrefMedlineGoogle Scholar2. Mahida S, Derval N, Sacher F, Berte B, Yamashita S, Hooks DA, Denis A, Lim H, Amraoui S, Aljefairi N, Hocini M, Jais P, Haissaguerre M. History and clinical significance of early repolarization syndrome.Heart Rhythm. 2015; 12:242–249. doi: 10.1016/j.hrthm.2014.09.048CrossrefMedlineGoogle Scholar3. 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Mechanisms underlying the development of the electrocardiographic and arrhythmic manifestations of early repolarization syndrome.J Mol Cell Cardiol. 2014; 68:20–28. doi: 10.1016/j.yjmcc.2013.12.012CrossrefMedlineGoogle Scholar7. Holland RP, Arnsdorf MF. Solid angle theory and the electrocardiogram: physiologic and quantitative interpretations.Prog Cardiovasc Dis. 1977; 19:431–457.CrossrefMedlineGoogle Scholar8. Nagase S, Tanaka M, Morita H, Nakagawa K, Wada T, Murakami M, Nishii N, Nakamura K, Ito H, Ohe T, Kusano KF. Local left ventricular epicardial J waves and late potentials in brugada syndrome patients with inferolateral early repolarization pattern.Front Physiol. 2017; 8:14. doi: 10.3389/fphys.2017.00014CrossrefMedlineGoogle Scholar9. Meijborg VM, Potse M, Conrath CE, Belterman CN, De Bakker JM, Coronel R. Reduced sodium current in the lateral ventricular wall induces inferolateral J-waves.Front Physiol. 2016; 7:365. doi: 10.3389/fphys.2016.00365CrossrefMedlineGoogle Scholar10. Potse M, Vinet A, Opthof T, Coronel R. Validation of a simple model for the morphology of the T wave in unipolar electrograms.Am J Physiol Heart Circ Physiol. 2009; 297:H792–H801. doi: 10.1152/ajpheart.00064.2009CrossrefMedlineGoogle Scholar11. Tokioka K, Kusano KF, Morita H, Miura D, Nishii N, Nagase S, Nakamura K, Kohno K, Ito H, Ohe T. Electrocardiographic parameters and fatal arrhythmic events in patients with Brugada syndrome: combination of depolarization and repolarization abnormalities.J Am Coll Cardiol. 2014; 63:2131–2138. doi: 10.1016/j.jacc.2014.01.072CrossrefMedlineGoogle Scholar12. Hoogendijk MG, Potse M, Linnenbank AC, et al. Mechanism of right precordial ST-segment elevation in structural heart disease: excitation failure by current-to-load mismatch.Heart Rhythm. 2010; 7:238–248. doi: 10.1016/j.hrthm.2009.10.007CrossrefMedlineGoogle Scholar13. Latcu DG, Bun SS, Zarqane N, Saoudi N. Ablation of left ventricular substrate in early repolarization syndrome.J Cardiovasc Electrophysiol. 2016; 27:490–491. doi: 10.1111/jce.12857CrossrefMedlineGoogle Scholar14. Lim PCY, Nademanee K, Lee ECY, Teo WS. Epicardial ablation utilizing remote magnetic navigation in a patient with Brugada syndrome and inferior early repolarization.Pacing Clin Electrophysiol. 2018; 41:214–217. doi: 10.1111/pace.13175CrossrefMedlineGoogle Scholar15. Maeda S, Yokoyama Y, Chik WW, Soejima K, Hirao K. First case of epicardial ablation to coexistent J waves in the inferior leads in a patient with clinical diagnosis of Brugada syndrome.HeartRhythm Case Rep. 2015; 1:82–84. doi: 10.1016/j.hrcr.2015.01.012CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Offerhaus J, Snelderwaard P, Algül S, Faber J, Riebel K, Jensen B and Boukens B (2021) High heart rate associated early repolarization causes J‐waves in both zebra finch and mouse, Physiological Reports, 10.14814/phy2.14775, 9:5, Online publication date: 1-Mar-2021. Coronel R, Potse M, Haïssaguerre M, Derval N, Rivaud M, Meijborg V, Cluitmans M, Hocini M and Boukens B (2021) Why Ablation of Sites With Purkinje Activation Is Antiarrhythmic: The Interplay Between Fast Activation and Arrhythmogenesis, Frontiers in Physiology, 10.3389/fphys.2021.648396, 12 Boukens B, Potse M and Coronel R (2021) Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome, International Journal of Molecular Sciences, 10.3390/ijms22041570, 22:4, (1570) January 18, 2019Vol 124, Issue 2 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.118.314414PMID: 30653434 Originally publishedJanuary 17, 2019 KeywordsmyocardiumBrugada syndromeaction potentialsrisktherapeuticsPDF download Advertisement