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  • Review Article
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Ventricular arrhythmias and the His–Purkinje system

Nature Reviews Cardiology volume 13, pages 155–166 (2016)Cite this article

Subjects

Key Points

  • Ventricular arrhythmias are the most common cause of sudden death, and individual risk prediction is a major medical challenge

  • The His–Purkinje system constitutes a tiny fraction of the ventricular mass, but is specialized for rapid synchronous activation of both ventricles

  • The pathogenic role of the Purkinje system is disproportionately high; discrete excitations act as main triggers of ventricular fibrillation in individuals with structurally normal hearts and in patients with diseased hearts

  • Purkinje cells are known to have a unique electrophysiology involving complex intracellular Ca2+ cycling

  • Further characterization of arrhythmia mechanisms is needed to enable the development of targeted therapy

Abstract

Ventricular arrhythmias are a major cause of sudden death, which accounts for approximately half of cardiac mortality. The His–Purkinje system is composed of specialized cells responsible for the synchronous activation of the ventricles. However, experimental studies show that the Purkinje system can be arrhythmogenic during electrolyte imbalance, after exposure to various drugs, and in myocardial ischaemia, during which Purkinje cells can survive in anaerobic conditions. Purkinje cells can generate both automatic and triggered focal rhythms, and their network configuration can accommodate re-entrant circuits. In humans, a variety of monomorphic ventricular tachycardias can be sustained within the architecture of the Purkinje branches. Furthermore, discrete Purkinje sources can serve as critical triggers of ventricular fibrillation in a wide spectrum of patients with structural heart disease or with an apparently normal heart. In drug-resistant cases of monomorphic and polymorphic Purkinje-related ventricular tachycardias, catheter ablation is a very effective treatment. The specific transcriptional signatures and functional properties of Purkinje cells, including their intracellular calcium dynamics, underlie their extreme arrhythmogenicity. However, the identification of vulnerable individuals remains challenging, and the molecular mechanisms of Purkinje-related arrhythmias have to be characterized further to enable the development of interventions to prevent lethal cardiac arrhythmias.

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Figure 1: Anatomy of the His–Purkinje system.
Figure 2: Evidence for a multichannel Ca2+-release function in Purkinje cells.
Figure 3: Spontaneous Ca2+ activity in Purkinje cells after myocardial infarction.
Figure 4: Typical regional Ca2+ activity in Purkinje cells.
Figure 5: Schematic representation of Purkinje re-entry.
Figure 6: Electrical mapping of the trigger of VF.

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References

  1. John, R. M. et al. Ventricular arrhythmias and sudden cardiac death. Lancet 380, 1520–1529 (2012).

    Article  PubMed  Google Scholar 

  2. Marsman, R. F., Tan, H. L. & Bezzina, C. R. Genetics of sudden cardiac death caused by ventricular arrhythmias. Nat. Rev. Cardiol. 11, 96–111 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. Tung, P. & Albert, C. M. Causes and prevention of sudden cardiac death in the elderly. Nat. Rev. Cardiol. 10, 135–142 (2013).

    Article  PubMed  Google Scholar 

  4. Silverman, M. E., Grove, D., Upshaw, C. B. Jr. Why does the heart beat? The discovery of the electrical system of the heart. Circulation 113, 2775–2781 (2006).

    Article  PubMed  Google Scholar 

  5. Scheinman, M. M. Role of the His−Purkinje system in the genesis of cardiac arrhythmia. Heart Rhythm 6, 1050–1058 (2009).

    Article  PubMed  Google Scholar 

  6. Boyden, P. A., Hirose, M. & Dun, W. Cardiac Purkinje cells. Heart Rhythm 7, 127–135 (2010).

    Article  PubMed  Google Scholar 

  7. Ono, N. et al. Morphological varieties of the Purkinje fiber network in mammalian hearts, as revealed by light and electron microscopy. Arch. Histol. Cytol. 72, 139–149 (2009).

    Article  PubMed  Google Scholar 

  8. Demoulin, J. C. & Kulbertus, H. E. Histopathological examination of concept of left hemiblock. Br. Heart J. 34, 807–814 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Christoffels, V. M. & Moorman, A. F. Development of the cardiac conduction system: why are some regions of the heart more arrhythmogenic than others? Circ. Arrhythm. Electrophysiol. 2, 195–207 (2009).

    Article  PubMed  Google Scholar 

  10. Dobrzynski, H. et al. Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues. Pharmacol. Ther. 139, 260–288 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. Sommer, J. R. & Johnson, E. A. A comparative study of Purkinje fibers and ventricular fibers. J. Cell Biol. 36, 497–526 (1968).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Eisenberg, B. R. & Cohen, I. S. The ultrastructure of the cardiac Purkinje strand in the dog: a morphometric analysis. Proc. R. Soc. Lond. B Biol. Sci. 217, 191–213 (1983).

    Article  CAS  PubMed  Google Scholar 

  13. Sommer, J. R. & Johnson, E. A. Purkinje fibers of the heart examined with the peroxidase reaction. J. Cell Biol. 37, 570–574 (1968).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Desplantez, T., Dupont, E., Severs, N. J. & Weingart, R. Gap junction channels and cardiac impulse propagation. J. Membr. Biol. 218, 13–28 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Gourdie, R. G. et al. The spatial distribution and relative abundance of gap-junctional connexin40 and connexin43 correlate to functional properties of components of the cardiac atrioventricular conduction system. J. Cell Sci. 105, 985–991 (1993).

    CAS  PubMed  Google Scholar 

  16. Gaborit, N. et al. Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart. J. Physiol. 582, 675–693 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gintant, G. A., Datyner, N. B. & Cohen, I. S. Slow inactivation of a tetrodotoxin-sensitive current in canine cardiac Purkinje fibers. Biophys. J. 45, 509–512 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Stuyvers, B. D. et al. Ca2+ sparks and waves in canine Purkinje cells: a triple layered system of Ca2+ activation. Circ. Res. 97, 35–43 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dun, W. & Boyden, P. A. The Purkinje cell; 2008 style. J. Mol. Cell Cardiol. 45, 617–624 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ter Keurs, H. E. & Boyden, P. A. Calcium and arrhythmogenesis. Physiol. Rev. 87, 457–506 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Segers, M. Le battement auto-entretenu du cœur [French]. Arch. Int. Pharmacodyn. 75, 144–156 (1947).

    CAS  PubMed  Google Scholar 

  22. Cranefield, P. F. Action potentials, afterpotentials, and arrhythmias. Circ. Res. 41, 415–423 (1977).

    Article  CAS  PubMed  Google Scholar 

  23. Song, Z., Ko, C. Y., Nivala, M., Weiss, J. N. & Qu, Z. Calcium-voltage coupling in the genesis of early and delayed afterdepolarizations in cardiac myocytes. Biophys. J. 108, 1908–1921 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hirose, M., Stuyvers, B. D., Dun, W., Ter Keurs, H. E. D. J. & Boyden, P. A. Function of Ca2+ release channels in purkinje cells that survive in the infarcted canine heart: a mechanism for triggered Purkinje ectopy. Circ. Arrhythm. Electrophysiol. 1, 387–395 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. De Lange, E., Xie, Y. & Qu, Z. Synchronization of early afterdepolarizations and arrhythmogenesis in heterogeneous cardiac tissue models. Biophys. J. 103, 365–373 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nivala, M., Ko, C. Y., Nivala, M., Weiss, J. N. & Qu, Z. Criticality in intracellular calcium signaling in cardiac myocytes. Biophys. J. 102, 2433–2442 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Maguy, A. et al. Ion channel subunit expression changes in cardiac Purkinje fibers: a potential role in conduction abnormalities associated with congestive heart failure. Circ. Res. 104, 1113–1122 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Deo, M., Boyle, P. M., Kim, A. M. & Vigmond, E. J. Arrhythmogenesis by single ectopic beats originating in the Purkinje system. Am. J. Physiol. Heart Circ. Physiol. 299, H1002–H1011 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tranum-Jensen, J., Wilde, A. A., Vermeulen, J. T. & Janse, M. J. Morphology of electrophysiologically identified junctions between Purkinje fibers and ventricular muscle in rabbit and pig hearts. Circ. Res. 69, 429–437 (1991).

    Article  CAS  PubMed  Google Scholar 

  30. Martinez-Palomo, A., Alanis, J. & Benitex, D. Transitional cardiac cells of the conductive system of the dog heart: distinguishing morphological and electrophysiological features. J. Cell Biol. 47, 1–17 (1970).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Joyner, R. W. & Overholt, E. D. Effects of octanol on canine subendocardial Purkinje-to-ventricular transmission. Am. J. Physiol. 249, H1228–H1231 (1985).

    CAS  PubMed  Google Scholar 

  32. Boyle, P. M., Vigmond, E. J. An intuitive safety factor for cardiac propagation. Biophys. J. 98, L57–L59 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gilmour, R. F. Jr & Moïse, N. S. Triggered activity as a mechanism for inherited ventricular arrhythmias in German shepherd Dogs. J. Am. Coll. Cardiol. 27, 1526–1533 (1996).

    Article  PubMed  Google Scholar 

  34. Myerburg, R. J., Nilsson, K. & Gelband, H. Physiology of canine intraventricular conduction and endocardial excitation. Circ. Res. 30, 217–243 (1972).

    Article  CAS  PubMed  Google Scholar 

  35. Myerburg, R. J., Stewart, J. W. & Hoffman, B. F. Electrophysiological properties of the canine peripheral A-V conducting system. Circ. Res. 26, 361–378 (1970).

    Article  CAS  PubMed  Google Scholar 

  36. Overholt, E. D., Joyner, R. W., Veenstra, R. D., Rawling, D. & Wiedmann, R. Unidirectional block between Purkinje and ventricular layers of papillary muscles. Am. J. Physiol. 247, H584–H595 (1984).

    CAS  PubMed  Google Scholar 

  37. Morley, G. E. et al. Reduced intercellular coupling leads to paradoxical propagation across the Purkinje−ventricular junction and aberrant myocardial activation. Proc. Natl Acad. Sci. USA 102, 4126–4129 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rohr, S., Kucera, J. P., Fast, V. G. & Kléber, A. G. Paradoxical improvement of impulse conduction in cardiac tissue by partial cellular uncoupling. Science 275, 841–844 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Tusscher, K. H. & Panfilov, A. V. Modelling of the ventricular conduction system. Prog. Biophys. Mol. Biol. 96, 152–170 (2008).

    Article  PubMed  Google Scholar 

  40. Berenfeld, O. & Jalife, J. Purkinje-muscle reentry as a mechanism of polymorphic ventricular arrhythmias in a 3-dimensional model of the ventricles. Circ. Res. 82, 1063–1077 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. Kusa, S. et al. Bundle branch reentrant ventricular tachycardia with wide and narrow QRS morphology. Circ. Arrhythm. Electrophysiol. 6, e87–e91 (2013).

    Article  PubMed  Google Scholar 

  42. Mizusawa, Y. et al. Characteristics of bundle branch reentrant ventricular tachycardia with a right bundle branch block configuration: feasibility of atrial pacing. Europace 11, 1208–1213 (2009).

    Article  PubMed  Google Scholar 

  43. Schmidt, B. et al. Left bundle branch−Purkinje system in patients with bundle branch reentrant tachycardia: lessons from catheter ablation and electroanatomic mapping. Heart Rhythm 6, 51–58 (2009).

    Article  PubMed  Google Scholar 

  44. Nogami, A. Purkinje-related arrhythmias part I: monomorphic ventricular tachycardias. Pacing Clin. Electrophysiol. 34, 624–650 (2011).

    Article  PubMed  Google Scholar 

  45. Belhassen, B., Rotmensch, H. H. & Laniado, S. Response of recurrent sustained ventricular tachycardia to verapamil. Br. Heart J. 46, 679–682 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yeh, S. J., Wen, M. S., Wang, C. C., Lin, F. C. & Wu, D. Adenosine-sensitive ventricular tachycardia from the anterobasal left ventricle. J. Am. Coll. Cardiol. 30, 1339–1345 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Ip, J. E. et al. Unifying mechanism of sustained idiopathic atrial and ventricular annular tachycardia. Circ. Arrhythm. Electrophysiol. 7, 436–444 (2014).

    Article  PubMed  Google Scholar 

  48. Tsuchiya, T. et al. Significance of late diastolic potential preceding Purkinje potential in verapamil-sensitive idiopathic left ventricular tachycardia. Circulation 99, 2408–2413 (1999).

    Article  CAS  PubMed  Google Scholar 

  49. Morishima, I., Norgami, A., Tsuboi, H. & Sone, T. Verapamil-sensitive left anterior fascicular ventricular tachycardia associated with a healed myocardial infarction: changes in the delayed Purkinje potential during sinus rhythm. J. Interv. Card. Electrophysiol. 22, 233–237 (2008).

    Article  PubMed  Google Scholar 

  50. Tsuchiya, T., Okumura, K., Honda, T., Iwasa, A. & Ashikaga, K. Effects of verapamil and lidocaine on two components of the re-entry circuit of verapamil-senstitive idiopathic left ventricular tachycardia. J. Am. Coll. Cardiol. 37, 1415–1421 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Friedman, P. L., Stewart, J. R., Fenoglio, J. J. Jr & Wit, A. L. Survival of subendocardial Purkinje fibers after extensive myocardial infarction in dogs. Circ. Res. 33, 597–611 (1973).

    Article  CAS  PubMed  Google Scholar 

  52. Lazzara, R., el-Sherif, N. & Scherlag, B. J. Electrophysiological properties of canine Purkinje cells in one-day-old myocardial infarction. Circ. Res. 33, 722–734 (1973).

    Article  CAS  PubMed  Google Scholar 

  53. Scherlag, B. J., El-Sherif, N., Hope, R. & Lazzara, R. Characterization and localization of ventricular arrhythmias resulting from myocardial ischemia and infarction. Circ. Res. 35, 372–383 (1974).

    Article  CAS  PubMed  Google Scholar 

  54. Janse, M. J. & Kléber, A. G. Electrophysiological changes and ventricular arrhythmias in the early phase of regional myocardial ischemia. Circ. Res. 49, 1069–1081 (1981).

    Article  CAS  PubMed  Google Scholar 

  55. El-Sherif, N., Mehra, R., Gough, W. B. & Zeiler, R. H. Ventricular activation patterns of spontaneous and induced ventricular rhythms in canine one-day-old myocardial infarction. Evidence for focal and reentrant mechanisms. Circ. Res. 51, 152–166 (1982).

    Article  CAS  PubMed  Google Scholar 

  56. Gilmour, R. F. Jr, Evans, J. J. & Zipes, D. P. Purkinje-muscle coupling and endocardial response to hyperkalemia, hypoxia, and acidosis. Am. J. Physiol. 247, H303–H311 (1984).

    PubMed  Google Scholar 

  57. Janse, M. J., Kleber, A. G., Capucci, A., Coronel, R. & Wilms-Schopman, F. Electrophysiological basis for arrhythmias caused by acute ischemia: role of the subendocardium. J. Mol. Cell Cardiol. 18, 339–355 (1986).

    Article  CAS  PubMed  Google Scholar 

  58. Dean, J. W. & Lab, M. J. Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology. Lancet 1, 1309–1311 (1989).

    Article  CAS  PubMed  Google Scholar 

  59. Han, W., Chartier, D., Li, D. & Nattel, S. Ionic remodeling of cardiac Purkinje cells by congestive heart failure. Circulation 104, 2095–2100 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Nattel, S., Maguy, A., Le Bouter, S. & Yeh, Y. H. Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol. Rev. 87, 425–456 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Cerrone, M. et al. Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia. Circ. Res. 101, 1039–1048 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kang, G. et al. Purkinje cells from RyR2 mutant mice are highly arrhythmogenic but responsive to targeted therapy. Circ. Res. 107, 512–519 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. El-Sherif, N., Zeiler, R. H., Craelius, W., Gough, W. B. & Henkin, R. QTU prolongation and polymorphic ventricular tachyarrhythmias due to bradycardia dependent early afterdepolarizations. Circul. Res. 63, 286–305 (1988).

    Article  CAS  Google Scholar 

  64. El-Sherif, N., Caref, E. B., Yin, H. & Restivo, M. The electrophysiological mechanism of ventricular tachyarrhythmias in the long QT syndrome: tridimensional mapping of activation and recovery patterns. Circul. Res. 79, 474–492 (1996).

    Article  CAS  Google Scholar 

  65. Asano, Y., Davidenko, J. M., Baxter, W. T., Gary, R. A. & Jalife, J. Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart. J. Am. Coll. Cardiol. 29, 831–842 (1997).

    Article  CAS  PubMed  Google Scholar 

  66. Choi, B. R., Burton, F. & Salama, G. Cytosolic Ca2+ triggers early afterdepolarization and torsade de pointes in rabbit hearts with type 2 long QT syndrome. J. Physiol. 543, 615–631 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Maruyama, M. et al. Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: role of Purkinje fibers and triggered activity. Circ. Res. 106, 399–408 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Haïssaguerre, M. et al. Role of Purkinje conducting system in triggering idiopathic sudden cardiac death. Lancet 359, 677–678 (2002).

    Article  PubMed  Google Scholar 

  69. Haïssaguerre, M. et al. Mapping and ablation of idiopathic ventricular fibrillation. Circulation 106, 962–967 (2002).

    Article  PubMed  Google Scholar 

  70. Nogami, A., Sugiyasu, A., Kubota, S. & Kato, K. Mapping and ablation of idiopathic ventricular fibrillation from the Purkinje system. Heart Rhythm 2, 646–649 (2005).

    Article  PubMed  Google Scholar 

  71. Szumowski, L. et al. Mapping and ablation of polymorphic ventricular tachycardia after myocardial infarction. J. Am. Coll. Cardiol. 4, 1700–1706 (2004).

    Article  Google Scholar 

  72. Marrouche, N. F. et al. Mode of initiation and ablation of ventricular fibrillation storms in patients with ischemic cardiomyopathy. J. Am. Coll. Cardiol. 43, 1715–1720 (2004).

    Article  PubMed  Google Scholar 

  73. Peichl, P. et al. Catheter ablation of arrhythmic storm triggered by monomorphic ectopic beats in patients with coronary artery disease. J. Interv. Card. Electrophysiol. 27, 51–59 (2010).

    Article  PubMed  Google Scholar 

  74. Kozeluhova, M. et al. Catheter ablation of electrical storm in patients with structural heart disease. Europace 13, 109–113 (2011).

    Article  PubMed  Google Scholar 

  75. Bode, K. et al. Ablation of polymorphic ventricular tachycardias in patients with structural heart disease. Pacing Clin. Electrophysiol. 31, 1585–1591 (2008).

    Article  PubMed  Google Scholar 

  76. Deneke, T. et al. Catheter ablation of electrical storm in a collaborative hospital network. Am. J. Cardiol. 108, 233–239 (2011).

    Article  PubMed  Google Scholar 

  77. Enjoji, Y. et al. Catheter ablation of fatal ventricular tachyarrhythmias storm in acute coronary syndrome — role of Purkinje fiber network. J. Interv. Card. Electrophysiol. 26, 207–215 (2009).

    Article  PubMed  Google Scholar 

  78. Nogami, A., Kubota, S., Adachi, M. & Igawa, O. Electrophysiologic and histopathologic findings of the ablation sites for ventricular fibrillation in a patient with ischemic cardiomyopathy. J. Interv. Card. Electrophysiol. 24, 133–137 (2009).

    Article  PubMed  Google Scholar 

  79. Koz´luk, E. et al. Efficacy of catheter ablation in patients with an electrical storm. Kardiol. Pol. 69, 665–670 (2011).

    Google Scholar 

  80. Sinha, A. M. et al. Role of left ventricular scar and Purkinje-like potentials during mapping and ablation of ventricular fibrillation in dilated cardiomyopathy. Pacing Clin. Electrophysiol. 32, 286–290 (2009).

    Article  PubMed  Google Scholar 

  81. Santoro, F. et al. Ventricular fibrillation triggered by PVCs from papillary muscles: clinical features and ablation. J. Cardiovasc. Electrophysiol. 25, 1158–1164 (2014).

    Article  PubMed  Google Scholar 

  82. Van Herendael, H. et al. Catheter ablation of ventricular fibrillation: importance of left ventricular outflow tract and papillary muscle triggers. Heart Rhythm 11, 566–573 (2014).

    Article  PubMed  Google Scholar 

  83. Yokoshiki, H., Mitsuyama, H., Watanabe, M., Sakurai, M. & Tsutsui, H. Pleomorphic ventricular tachycardia originating from Purkinje fiber network of left anterior fascicle. J. Electrocardiol. 43, 452–458 (2010).

    Article  PubMed  Google Scholar 

  84. Li, Y. G., Grönefeld, G., Israel, C. & Hohnloser, S. H. Catheter ablation of frequently recurring ventricular fibrillation in a patient after aortic valve repair. J. Cardiovasc. Electrophysiol. 15, 90–93 (2004).

    Article  PubMed  Google Scholar 

  85. Mlcochova, H. et al. Catheter ablation of ventricular fibrillation storm in patients with infiltrative amyloidosis of the heart. J. Cardiovasc. Electrophysiol. 17, 426–430 (2006).

    Article  PubMed  Google Scholar 

  86. Nakabayashi, K., Sugiura, R. & Oka, T. Catheter ablation targeting Purkinje potentials controlled ventricular fibrillation in a patient with a malignant lymphoma occurring in the ventricular septum. BMJ Case Rep. http://dx.doi.org/10.1136/bcr-2014-209026.

  87. Leenhardt, A. et al. Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation 91, 1512–1519 (1995).

    Article  CAS  PubMed  Google Scholar 

  88. Priori, S. G. et al. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103, 196–200 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Kaneshiro, T. et al. Successful catheter ablation of bidirectional ventricular premature contractions triggering ventricular fibrillation in catecholaminergic polymorphic ventricular tachycardia with RyR2 mutation. Circ. Arrhythm. Electrophysiol. 5, e14–e17 (2012).

    Article  PubMed  Google Scholar 

  90. Roche, M., Renauleaud, C., Ballet, V., Doubovetzky, M. & Guillon, J. M. The isolated rabbit heart and Purkinje fibers as models for identifying proarrhythmic liability. J. Pharmacol. Toxicol. Methods 61, 238–250 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Nogami, A. Purkinje-related arrhythmias part II: polymorphic ventricular tachycardia and ventricular fibrillation. Pacing Clin. Electrophysiol. 34, 1034–1049 (2011).

    Article  PubMed  Google Scholar 

  92. Srivathsan, K., Gami, A. S., Ackerman, M. J. & Asirvatham, S. J. Treatment of ventricular fibrillation in a patient with prior diagnosis of long QT syndrome: importance of precise electrophysiologic diagnosis to successfully ablate the trigger. Heart Rhythm 4, 1090–1093 (2007).

    Article  PubMed  Google Scholar 

  93. Tan, V. H., Yap, J., Hsu, L. F. & Liew, R. Catheter ablation of ventricular fibrillation triggers and electrical storm. Europace 14, 1687–1695 (2012).

    Article  PubMed  Google Scholar 

  94. Sanchez-Munoz, J. J. et al. Ablation of premature ventricular complexes Triggering Ventricular Fibrillation in a patient with long QT syndrome. Indian Pacing Electrophysiol. J. 11, 81–83 (2011).

    PubMed  PubMed Central  Google Scholar 

  95. Haissaguerre, M. et al. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada Syndromes. Circulation 108, 925–928 (2003).

    Article  PubMed  Google Scholar 

  96. Knecht, S. et al. Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study. J. Am. Coll. Cardiol. 54, 522–528 (2009).

    Article  PubMed  Google Scholar 

  97. Yagishita, A., Yamauchi, Y., Obayashi, T. & Hirao, K. Idiopathic ventricular fibrillation associated with early repolarization which was unmasked by a sodium channel blocker after catheter ablation of atrial fibrillation. J. Interv. Card. Electrophysiol. 41, 145–146 (2014).

    Article  PubMed  Google Scholar 

  98. Pasquié, J. L. et al. Fever as a precipitant of idiopathic ventricular fibrillation in patients with normal hearts. J. Cardiovasc. Electrophysiol. 15, 1271–1276 (2004).

    Article  PubMed  Google Scholar 

  99. Kimura, T. et al. Ventricular fibrillation associated with J-wave manifestation following pericarditis after catheter ablation for paroxysmal atrial fibrillation. Can. J. Cardiol. 29, 1330.e1–1330.e3 (2013).

    Article  Google Scholar 

  100. Huang, J. et al. The importance of Purkinje activation in long duration ventricular fibrillation. J. Am. Heart Assoc. 3, e000495 (2014).

    PubMed  PubMed Central  Google Scholar 

  101. Lin, C. et al. Endocardial focal activation originating from Purkinje fibers plays a role in the maintenance of long duration ventricular fibrillation. Croat. Med. J. 55, 121–127 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Sivagangabalan, G. et al. Regional ion channel gene expression heterogeneity and ventricular fibrillation dynamics in human hearts. PLoS ONE 9, e82179 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Li, L. et al. Different types of long-duration ventricular fibrillation: can they be identified by electrocardiography. J. Electrocardiol. 45, 658–659 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Boyle, P. M., Massé, S., Nanthakumar, K. & Vigmond, E. J. Transmural IK(ATP) heterogeneity as a determinant of activation rate gradient during early ventricular fibrillation: mechanistic insights from rabbit ventricular models. Heart Rhythm 10, 1710–1717 (2013).

    Article  PubMed  Google Scholar 

  105. Damiano, R. J. Jr et al. The effect of chemical ablation of the endocardium on ventricular fibrillation threshold. Circulation 74, 645–652 (1986).

    Article  PubMed  Google Scholar 

  106. Dosdall, D. J. et al. Chemical ablation of the Purkinje system causes early termination and activation rate slowing of long-duration ventricular fibrillation in dogs. Am. J. Physiol. Heart Circ. Physiol. 295, H883–H889 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Pak, H. N. et al. Both Purkinje cells and left ventricular posteroseptal reentry contribute to the maintenance of ventricular fibrillation in open-chest dogs and swine: effects of catheter ablation and the ventricular cut-and-sew operation. Circ. J. 72, 1185–1192 (2008).

    Article  PubMed  Google Scholar 

  108. Zamiri, N. et al. Dantrolene improves survival after ventricular fibrillation by mitigating impaired calcium handling in animal models. Circulation 129, 875–885 (2014).

    Article  CAS  PubMed  Google Scholar 

  109. Lowery, C. M. Use of stored implanted cardiac defibrillator electrograms in catheter ablation of ventricular fibrillation. Pacing Clin. Electrophysiol. 36, 76–85 (2013).

    Article  PubMed  Google Scholar 

  110. Xiao, L. et al. Unique cardiac Purkinje fiber transient outward current β-subunit composition: a potential molecular link to idiopathic ventricular fibrillation. Circ. Res. 112, 1310–1322 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Marsman, R. F. et al. A mutation in CALM1 encoding calmodulin in familial idiopathic ventricular fibrillation in childhood and adolescence. J. Am. Coll. Cardiol. 3, 259–266 (2014).

    Article  CAS  Google Scholar 

  112. Cheung, J. W. et al. Short-coupled polymorphic ventricular tachycardia at rest linked to a novel ryanodine receptor (RyR2) mutation: leaky RyR2 channels under non-stress conditions. Int. J. Cardiol. 180, 228–236 (2015).

    Article  PubMed  Google Scholar 

  113. Tamargo, J., Caballero, R., Gomez, R., Valenzuela, C. & Delpon, E. Pharmacology of cardiac potassium channels. Cardiovasc. Res. 62, 9–33 (2004).

    Article  CAS  PubMed  Google Scholar 

  114. Caceres, J. et al. Sustained bundle branch reentry as a mechanism of clinical tachycardia. Circulation 79, 256–270 (1989).

    Article  CAS  PubMed  Google Scholar 

  115. Wissner, E. et al. Long-term outcome after catheter ablation for left posterior fascicular ventricular tachycardia without development of left posterior fascicular block. J. Cardiovasc. Electrophysiol. 23, 1179–1184 (2012).

    Article  PubMed  Google Scholar 

  116. Belhassen, B. & Viskin, S. Idiopathic ventricular tachycardia and fibrillation. J. Cardiovasc. Electrophysiol. 4, 356–368 (1993).

    Article  CAS  PubMed  Google Scholar 

  117. Bogun, F. et al. Role of Purkinje fibers in post-infarction ventricular tachycardia. J. Am. Coll. Cardiol. 48, 2500–2507 (2006).

    Article  PubMed  Google Scholar 

  118. Hayashi, M. et al. Novel mechanism of postinfarction ventricular tachycardia originating in surviving left posterior Purkinje fibers. Heart Rhythm 3, 908–918 (2006).

    Article  PubMed  Google Scholar 

  119. Bansch, D. et al. Successful catheter ablation of electrical storm after myocardial infarction. Circulation 108, 3011–3016 (2003).

    Article  PubMed  Google Scholar 

  120. Yokoshiki, H., Mitsuyama, H., Watanabe, M., Mizukami, K. & Tsutsui, H. Suppression of ventricular fibrillation by electrical modification of the Purkinje system in hypertrophic cardiomyopathy. Heart Vessels 29, 709–717 (2014).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Hôpital Cardiologique du Haut Lévêque, Avenue de Magellan, Pessac Cedex, 33604, France

    Michel Haissaguerre & Meleze Hocini

  2. IHU LIRYC, Site Xavier Arnozan, Avenue du Haut Lévêque, Pessac, 33600, France

    Edward Vigmond, Bruno Stuyvers & Olivier Bernus

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  1. Michel Haissaguerre
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  2. Edward Vigmond
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  3. Bruno Stuyvers
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  4. Meleze Hocini
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  5. Olivier Bernus
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Contributions

M. Haissaguerre, E.V., B.S., M. Hocini, and O.B. researched data for the article. M. Haissaguerre, E.V., B.S., and O.B. wrote the article. M. Haissaguerre and O.B. reviewed and edited the manuscript before submission.

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Correspondence to Michel Haissaguerre.

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Haissaguerre, M., Vigmond, E., Stuyvers, B. et al. Ventricular arrhythmias and the His–Purkinje system. Nat Rev Cardiol 13, 155–166 (2016). https://doi.org/10.1038/nrcardio.2015.193

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